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Sample records for nanoparticle delivery system

  1. Protamine-based nanoparticles as new antigen delivery systems.

    Science.gov (United States)

    González-Aramundiz, José Vicente; Peleteiro Olmedo, Mercedes; González-Fernández, África; Alonso Fernández, María José; Csaba, Noemi Stefánia

    2015-11-01

    The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Nanoparticle-based drug delivery systems: promising approaches against infections

    International Nuclear Information System (INIS)

    Ranghar, Shweta; Sirohi, Parul; Verma, Pritam; Agarwal, Vishnu

    2014-01-01

    Despite the fact that many new drugs and technologies have been developed to combat the infectious diseases, these have continued to be global health challenges. The use of conventional antimicrobial agents against these infections is always associated with problems such as the development of multiple drug resistance and adverse side effects. In addition, the inefficient traditional drug delivery system results in inadequate therapeutic index, low bioavailability of drugs and many other limitations. In this regard, antimicrobial nanoparticles and nanosized drug delivery carriers have emerged as potent effective agents against the infections. Nanoparticles have unique properties owing to their ultra small and controllable size such as high surface area, enhanced reactivity, and functionalizable structure. This review focused on different classes of antimicrobial nanoparticles, including metal, metal oxide and others along with their mechanism of action and their potential use against the infections. The review also focused on the development of nanoparticle systems for antimicrobial drug delivery and use of these systems for delivery of various antimicrobial agents, giving an overview about modern nanoparticle based therapeutic strategies against the infections. (author)

  3. Nanoparticle-based drug delivery systems: promising approaches against infections

    Energy Technology Data Exchange (ETDEWEB)

    Ranghar, Shweta; Sirohi, Parul [Department of Applied Mechanics, Motilal Nehru National Institute of Technology, Allahabad (India); Verma, Pritam; Agarwal, Vishnu [Department of Biotechnology, Motilal Nehru National Institute of Technology, Allahabad (India)

    2014-03-15

    Despite the fact that many new drugs and technologies have been developed to combat the infectious diseases, these have continued to be global health challenges. The use of conventional antimicrobial agents against these infections is always associated with problems such as the development of multiple drug resistance and adverse side effects. In addition, the inefficient traditional drug delivery system results in inadequate therapeutic index, low bioavailability of drugs and many other limitations. In this regard, antimicrobial nanoparticles and nanosized drug delivery carriers have emerged as potent effective agents against the infections. Nanoparticles have unique properties owing to their ultra small and controllable size such as high surface area, enhanced reactivity, and functionalizable structure. This review focused on different classes of antimicrobial nanoparticles, including metal, metal oxide and others along with their mechanism of action and their potential use against the infections. The review also focused on the development of nanoparticle systems for antimicrobial drug delivery and use of these systems for delivery of various antimicrobial agents, giving an overview about modern nanoparticle based therapeutic strategies against the infections. (author)

  4. Lipid nanoparticles as drug/gene delivery systems to the retina.

    Science.gov (United States)

    del Pozo-Rodríguez, Ana; Delgado, Diego; Gascón, Alicia R; Solinís, Maria Ángeles

    2013-03-01

    This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug/gene delivery systems for retinal diseases. Most drug products for ocular disease treatment are marketed as eye drop formulations but, due to ocular barriers, the drug concentration in the retina hardly ever turns out to be effective. Up to this date, several delivery systems have been designed to deliver drugs to the retina. Drug delivery strategies may be classified into 3 groups: noninvasive techniques, implants, and colloidal carriers. The best known systems for drug delivery to the posterior eye are intravitreal implants; in fact, some of them are being clinically used. However, their long-term accumulation might impact the patient's vision. On the contrary, colloidal drug delivery systems (microparticles, liposomes, or nanoparticles) can be easily administered in a liquid form. Nanoparticular systems diffuse rapidly and are better internalized in ocular tissues than microparticles. In comparison with liposomes, nanoparticles have a higher loading capacity and are more stable in biological fluids and during storage. In addition, their capacity to adhere to the ocular surface and interact with the endothelium makes these drug delivery systems interesting as new therapeutic tools in ophthalmology. Within the group of nanoparticles, those composed of lipids (Solid Lipid Nanoparticles, Nanostructred Lipid Carriers, and Lipid Drug Conjugates) are more biocompatible, easy to produce at large scale, and they may be autoclaved or sterilized. The present review summarizes scientific results that evidence the potential application of lipid nanoparticles as drug delivery systems for the retina and also as nonviral vectors in gene therapy of retina disorders, although much more effort is still needed before these lipidic systems could be available in the market.

  5. Recent trends in drug delivery system using protein nanoparticles.

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    Sripriyalakshmi, S; Jose, Pinkybel; Ravindran, Aswathy; Anjali, C H

    2014-09-01

    Engineered nanoparticles that can facilitate drug formulation and passively target tumours have been under extensive research in recent years. These successes have driven a new wave of significant innovation in the generation of advanced particles. The fate and transport of diagnostic nanoparticles would significantly depend on nonselective drug delivery, and hence the use of high drug dosage is implemented. In this perspective, nanocarrier-based drug targeting strategies can be used which improve the selective delivery of drugs to the site of action, i.e. drug targeting. Pharmaceutical industries majorly focus on reducing the toxicity and side effects of drugs but only recently it has been realised that carrier systems themselves may pose risks to the patient. Proteins are compatible with biological systems and they are biodegradable. They offer a multitude of moieties for modifications to tailor drug binding, imaging or targeting entities. Thus, protein nanoparticles provide outstanding contributions as a carrier for drug delivery systems. This review summarises recent progress in particle-based therapeutic delivery and discusses important concepts in particle design and biological barriers for developing the next generation of particles drug delivery systems.

  6. Delivery Systems for Biopharmaceuticals. Part I: Nanoparticles and Microparticles.

    Science.gov (United States)

    Silva, Ana C; Lopes, Carla M; Lobo, José M S; Amaral, Maria H

    2015-01-01

    Pharmaceutical biotechnology has been showing therapeutic success never achieved with conventional drug molecules. Therefore, biopharmaceutical products are currently well-established in clinic and the development of new ones is expected. These products comprise mainly therapeutic proteins, although nucleic acids and cells are also included. However, according to their sensitive molecular structures, the efficient delivery of biopharmaceuticals is challenging. Several delivery systems (e.g. microparticles and nanoparticles) composed of different materials (e.g. polymers and lipids) have been explored and demonstrated excellent outcomes, such as: high cellular transfection efficiency for nucleic acids, cell targeting, increased proteins and peptides bioavailability, improved immune response in vaccination, and viability maintenance of microencapsulated cells. Nonetheless, important issues need to be addressed before they reach clinics. For example, more in vivo studies in animals, accessing the toxicity potential and predicting in vivo failure of these delivery systems are required. This is the Part I of two review articles, which presents the state of the art of delivery systems for biopharmaceuticals. Part I deals with microparticles and polymeric and lipid nanoparticles.

  7. Chitosan magnetic nanoparticles for drug delivery systems.

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    Assa, Farnaz; Jafarizadeh-Malmiri, Hoda; Ajamein, Hossein; Vaghari, Hamideh; Anarjan, Navideh; Ahmadi, Omid; Berenjian, Aydin

    2017-06-01

    The potential of magnetic nanoparticles (MNPs) in drug delivery systems (DDSs) is mainly related to its magnetic core and surface coating. These coatings can eliminate or minimize their aggregation under physiological conditions. Also, they can provide functional groups for bioconjugation to anticancer drugs and/or targeted ligands. Chitosan, as a derivative of chitin, is an attractive natural biopolymer from renewable resources with the presence of reactive amino and hydroxyl functional groups in its structure. Chitosan nanoparticles (NPs), due to their huge surface to volume ratio as compared to the chitosan in its bulk form, have outstanding physico-chemical, antimicrobial and biological properties. These unique properties make chitosan NPs a promising biopolymer for the application of DDSs. In this review, the current state and challenges for the application magnetic chitosan NPs in drug delivery systems were investigated. The present review also revisits the limitations and commercial impediments to provide insight for future works.

  8. Applications of nanoparticle systems in drug delivery technology

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    Syed A.A. Rizvi

    2018-01-01

    Full Text Available The development of nanoparticle-based drug formulations has yielded the opportunities to address and treat challenging diseases. Nanoparticles vary in size but are generally ranging from 100 to 500 nm. Through the manipulation of size, surface characteristics and material used, the nanoparticles can be developed into smart systems, encasing therapeutic and imaging agents as well as bearing stealth property. Further, these systems can deliver drug to specific tissues and provide controlled release therapy. This targeted and sustained drug delivery decreases the drug related toxicity and increase patient’s compliance with less frequent dosing. Nanotechnology has proven beneficial in the treatment of cancer, AIDS and many other disease, also providing advancement in diagnostic testing.

  9. An Effective Delivery System of Sitagliptin Using Optimized Mucoadhesive Nanoparticles

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    Afzal Haq Asif

    2018-05-01

    Full Text Available Sitagliptin (MK-0431, is a potent oral hypoglycemic drug that is used for treating type 2 diabetes mellitus. However, the short half-life of sitagliptin requires patients to take a high dose of 50 mg twice per day, and the fraction of sitagliptin reversibly bound to plasma proteins is as low as 38%. In addition, it was reported that approximately 79% of sitagliptin is excreted unchanged in the urine for elimination without metabolism. Thus, a better delivery system is needed to improve the benefits of sitagliptin in patients. The drug content and percentage yield were found to be 73 ± 2% and 92 ± 2%, respectively. The optimized sitagliptin nanoparticle sizes were between 350–950 nm, and the surfaces were smooth and nearly spherical in shape. In addition, the optimized sitagliptin nanoparticles have an indicated excellent bioadhesion property of (6.1 ± 0.5 h. The swelling of the nanoparticles is 168 ± 15%. The pattern of sitagliptin release from the mucoadhesive nanoparticles follows the Korsmeyer-Peppas model. More importantly, the extended sitagliptin retention time, of up to 12 h in the gastrointestinal tract, suggests that the optimized mucoadhesive nanoparticle formulation is more efficient, and has a greater potential to be used for oral delivery compared to the conventional sitagliptin administration in the drug solution. This is the first developed delivery system using the optimized mucoadhesive nanoparticles to enhance the effectiveness of sitagliptin.

  10. Intraventricular Delivery of siRNA Nanoparticles to the Central Nervous System

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    Rishab Shyam

    2015-01-01

    Full Text Available Alzheimer's disease (AD is a progressive neurodegenerative disease currently lacking effective treatment. Efficient delivery of siRNA via nanoparticles may emerge as a viable therapeutic approach to treat AD and other central nervous system disorders. We report here the use of a linear polyethyleneimine (LPEI-g-polyethylene glycol (PEG copolymer-based micellar nanoparticle system to deliver siRNA targeting BACE1 and APP, two therapeutic targets of AD. Using LPEI-siRNA nanoparticles against either BACE1 or APP in cultured mouse neuroblastoma (N2a cells, we observe selective knockdown, respectively, of BACE1 or APP. The encapsulation of siRNA by LPEI-g-PEG carriers, with different grafting degrees of PEG, leads to the formation of micellar nanoparticles with distinct morphologies, including worm-like, rod-like, or spherical nanoparticles. By infusing these shaped nanoparticles into mouse lateral ventricles, we show that rod-shaped nanoparticles achieved the most efficient knockdown of BACE1 in the brain. Furthermore, such knockdown is evident in spinal cords of these treated mice. Taken together, our findings indicate that the shape of siRNA-encapsulated nanoparticles is an important determinant for their delivery and gene knockdown efficiency in the central nervous system.

  11. Ultrasound mediated nanoparticle drug delivery

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    Mullin, Lee B.

    Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems

  12. Design and evaluate alginate nanoparticles as a protein delivery system

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    Saraei, F.

    2013-12-01

    Full Text Available In recent years, encapsulation of drugs and antigens in hydrogels, specifically in calcium alginate particles, is an interesting and practical technique that was developed widespread. It is well known that alginate solution, under proper conditions, can form suitable nanoparticles as a promising carrier system, for vaccine delivery. The aim of this study was to synthesis alginate nanoparticles as protein carrier and to evaluate the influence of various factors on nanoparticles properties. Alginate nanoparticles were prepared by ionic gelation method. Briefly, various concentrations of CaCl2 were added to different concentrations of sodium alginate dropwisly by homogenizing magnetically at 1300 rpm. The effects of homogenization time and (- rate were investigated on nanoparticle feature. Nanoparticles were characterized for their morphology and size distribution. Evaluation of loading capacity and loading efficiency of nanoparticles were performed by using various concentration of BSA. The concentration of 0.3%w/v sodium alginate and 0.1%w/v CaCl2 solution, homogenization time 45 min and homogenization rate 1300 rpm were observed as suitable condition - to prepare optimized nanoparticles. It can be concluded that the properties of nanoparticles are strongly dependent on the physicochemical conditions. The optimum concentrations of alginate and CaCl2and appropriate condition led to forming desirable nanoparticles that can be used as carrier for drug and vaccine delivery.

  13. Mucosal delivery of liposome-chitosan nanoparticle complexes.

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    Carvalho, Edison L S; Grenha, Ana; Remuñán-López, Carmen; Alonso, Maria José; Seijo, Begoña

    2009-01-01

    Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes. To overcome these limitations, we developed a new drug delivery system that results from the combination of chitosan nanoparticles and liposomes, in an approach of combining their advantages, while avoiding their individual limitations. These lipid/chitosan nanoparticle complexes are, thus, expected to protect the encapsulated drug from harsh environmental conditions, while concomitantly providing its controlled release. To prepare these assemblies, two different strategies have been applied: one focusing on the simple hydration of a previously formed dry lipid film with a suspension of chitosan nanoparticles, and the other relying on the lyophilization of both basic structures (nanoparticles and liposomes) with a subsequent step of hydration with water. The developed systems are able to provide a controlled release of the encapsulated model peptide, insulin, evidencing release profiles that are dependent on their lipid composition. Moreover, satisfactory in vivo results have been obtained, confirming the potential of these newly developed drug delivery systems as drug carriers through distinct mucosal routes.

  14. A sight on protein-based nanoparticles as drug/gene delivery systems.

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    Salatin, Sara; Jelvehgari, Mitra; Maleki-Dizaj, Solmaz; Adibkia, Khosro

    2015-01-01

    Polymeric nanomaterials have extensively been applied for the preparation of targeted and controlled release drug/gene delivery systems. However, problems involved in the formulation of synthetic polymers such as using of the toxic solvents and surfactants have limited their desirable applications. In this regard, natural biomolecules including proteins and polysaccharide are suitable alternatives due to their safety. According to literature, protein-based nanoparticles possess many advantages for drug and gene delivery such as biocompatibility, biodegradability and ability to functionalize with targeting ligands. This review provides a general sight on the application of biodegradable protein-based nanoparticles in drug/gene delivery based on their origins. Their unique physicochemical properties that help them to be formulated as pharmaceutical carriers are also discussed.

  15. Magnetic Nanoparticles of Chitosan for Targeted Delivery System of Plasmids to the Lungs

    International Nuclear Information System (INIS)

    Baez, C.A.A.; Cruz, I.E.L.; Padilla, M.C.R.; Gonzalez, J.M.A.

    2014-01-01

    One of the major problems of gene therapy is the efficient, specific, and targeted delivery as well as the safety of the materials used in such systems. The specific targeted delivery of genes to the lung offers the possibility to treat a variety of specific diseases. We developed chitosan nanoparticles with the plasmid pCEM-Luc, which contains a promoter activated by magnetic field. Nanoparticles of 200-250 nm obtained by ionic gelation with a 99% retention rate were transfected in B16F10 cells and in vivo in the lungs of Balb/c mice by intratracheal administration. We observed that an external magnetic field increased the expression of the luciferase reporter gene in B16F10 cells transfected with magnetic nanoparticles and in homogenized lungs of mice which determined differences in levels of expression between different regions of the lungs (apical or distal and left or right). The highest levels of luciferase activity were observed in the apical left region. The magnetic nanoparticles prove an efficient delivery system to in vitro transfection of cells and lung tissue.

  16. Hydrogel nanoparticles in drug delivery.

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    Hamidi, Mehrdad; Azadi, Amir; Rafiei, Pedram

    2008-12-14

    Hydrogel nanoparticles have gained considerable attention in recent years as one of the most promising nanoparticulate drug delivery systems owing to their unique potentials via combining the characteristics of a hydrogel system (e.g., hydrophilicity and extremely high water content) with a nanoparticle (e.g., very small size). Several polymeric hydrogel nanoparticulate systems have been prepared and characterized in recent years, based on both natural and synthetic polymers, each with its own advantages and drawbacks. Among the natural polymers, chitosan and alginate have been studied extensively for preparation of hydrogel nanoparticles and from synthetic group, hydrogel nanoparticles based on poly (vinyl alcohol), poly (ethylene oxide), poly (ethyleneimine), poly (vinyl pyrrolidone), and poly-N-isopropylacrylamide have been reported with different characteristics and features with respect to drug delivery. Regardless of the type of polymer used, the release mechanism of the loaded agent from hydrogel nanoparticles is complex, while resulting from three main vectors, i.e., drug diffusion, hydrogel matrix swelling, and chemical reactivity of the drug/matrix. Several crosslinking methods have been used in the way to form the hydrogel matix structures, which can be classified in two major groups of chemically- and physically-induced crosslinking.

  17. Solid Lipid Nanoparticles as Efficient Drug and Gene Delivery Systems: Recent Breakthroughs

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    Jafar Ezzati Nazhad Dolatabadi

    2015-06-01

    Full Text Available In recent years, nanomaterials have been widely applied as advanced drug and gene delivery nanosystems. Among them, solid lipid nanoparticles (SLNs have attracted great attention as colloidal drug delivery systems for incorporating hydrophilic or lipophilic drugs and various macromolecules as well as proteins and nucleic acids. Therefore, SLNs offer great promise for controlled and site specific drug and gene delivery. This article includes general information about SLN structures and properties, production procedures, characterization. In addition, recent progress on development of drug and gene delivery systems using SLNs was reviewed.

  18. Nanoparticles Engineered from Lecithin-in-Water Emulsions As A Potential Delivery System for Docetaxel

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    Yanasarn, Nijaporn; Sloat, Brian R.; Cui, Zhengrong

    2009-01-01

    Docetaxel is a potent anti-cancer drug. However, there continues to be a need for alternative docetaxel delivery systems to improve its efficacy. We reported the engineering of a novel spherical nanoparticle formulation (~270 nm) from lecithin-in-water emulsions. Docetaxel can be incorporated into the nanoparticles, and the resultant docetaxel-nanoparticles were stable when stored as an aqueous suspension. The release of the docetaxel from the nanoparticles was likely caused by a combination of diffusion and Case II transport. The docetaxel-in-nanoparticles were more effective in killing tumor cells in culture than free docetaxel. Moreover, the docetaxel-nanoparticles did not cause any significant red blood cell lysis or platelet aggregation in vitro, nor did they induce detectable acute liver damage when injected intravenously into mice. Finally, compared to free docetaxel, the intravenously injected docetaxel-nanoparticles increased the accumulation of the docetaxel in a model tumor in mice by 4.5-fold. These lecithin-based nanoparticles have the potential to be a novel biocompatible and efficacious delivery system for docetaxel. PMID:19524029

  19. Drug delivery and nanoparticles: Applications and hazards

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    Wim H De Jong

    2008-06-01

    Full Text Available Wim H De Jong1, Paul JA Borm2,31Laboratory for Toxicology, Pathology and Genetics, National Institute for Public Health and the Environment (RIVM, Bilthoven, The Netherlands; 2Zuyd University, Centre of Expertise in Life Sciences, Heerlen, The Netherlands; 3Magnamedics GmbH, Aachen, GermanyAbstract: The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation

  20. Aptamer-Gated Nanoparticles for Smart Drug Delivery

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    Huseyin Avni Oktem

    2011-08-01

    Full Text Available Aptamers are functional nucleic acid sequences which can bind specific targets. An artificial combinatorial methodology can identify aptamer sequences for any target molecule, from ions to whole cells. Drug delivery systems seek to increase efficacy and reduce side-effects by concentrating the therapeutic agents at specific disease sites in the body. This is generally achieved by specific targeting of inactivated drug molecules. Aptamers which can bind to various cancer cell types selectively and with high affinity have been exploited in a variety of drug delivery systems for therapeutic purposes. Recent progress in selection of cell-specific aptamers has provided new opportunities in targeted drug delivery. Especially functionalization of nanoparticles with such aptamers has drawn major attention in the biosensor and biomedical areas. Moreover, nucleic acids are recognized as an attractive building materials in nanomachines because of their unique molecular recognition properties and structural features. A active controlled delivery of drugs once targeted to a disease site is a major research challenge. Stimuli-responsive gating is one way of achieving controlled release of nanoparticle cargoes. Recent reports incorporate the structural properties of aptamers in controlled release systems of drug delivering nanoparticles. In this review, the strategies for using functional nucleic acids in creating smart drug delivery devices will be explained. The main focus will be on aptamer-incorporated nanoparticle systems for drug delivery purposes in order to assess the future potential of aptamers in the therapeutic area. Special emphasis will be given to the very recent progress in controlled drug release based on molecular gating achieved with aptamers.

  1. Sodium deoxycholate-decorated zein nanoparticles for a stable colloidal drug delivery system.

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    Gagliardi, Agnese; Paolino, Donatella; Iannone, Michelangelo; Palma, Ernesto; Fresta, Massimo; Cosco, Donato

    2018-01-01

    The use of biopolymers is increasing in drug delivery, thanks to the peculiar properties of these compounds such as their biodegradability, availability, and the possibility of modulating their physico-chemical characteristics. In particular, protein-based systems such as albumin are able to interact with many active compounds, modulating their biopharmaceutical properties. Zein is a protein of 20-40 kDa made up of many hydrophobic amino acids, generally regarded as safe (GRAS) and used as a coating material. In this investigation, zein was combined with various surfactants in order to obtain stable nanosystems by means of the nanoprecipitation technique. Specific parameters, eg, temperature, pH value, Turbiscan Stability Index, serum stability, in vitro cytotoxicity and entrapment efficiency of various model compounds were investigated, in order to identify the nanoformulation most useful for a systemic drug delivery application. The use of non-ionic and ionic surfactants such as Tween 80, poloxamer 188, and sodium deoxycholate allowed us to obtain nanoparticles characterized by a mean diameter of 100-200 nm when a protein concentration of 2 mg/mL was used. The surface charge was modulated by means of the protein concentration and the nature of the stabilizer. The most suitable nanoparticle formulation to be proposed as a colloidal drug delivery system was obtained using sodium deoxycholate (1.25% w/v) because it was characterized by a narrow size distribution, a good storage stability after freeze-drying and significant feature of retaining lipophilic and hydrophilic compounds. The sodium deoxycholate-coated zein nanoparticles are stable biocompatible colloidal carriers to be used as useful drug delivery systems.

  2. Magnetic chitosan nanoparticles as a drug delivery system for targeting photodynamic therapy

    International Nuclear Information System (INIS)

    Sun Yun; Chen Zhilong; Yang Xiaoxia; Huang Peng; Zhou Xinping; Du Xiaoxia

    2009-01-01

    Photodynamic therapy (PDT) has become an increasingly recognized alternative to cancer treatment in clinic. However, PDT therapy agents, namely photosensitizer (PS), are limited in application as a result of prolonged cutaneous photosensitivity, poor water solubility and inadequate selectivity, which are encountered by numerous chemical therapies. Magnetic chitosan nanoparticles provide excellent biocompatibility, biodegradability, non-toxicity and water solubility without compromising their magnetic targeting. Nevertheless, no previous attempt has been reported to develop an in vivo magnetic drug delivery system with chitosan nanoparticles for magnetic resonance imaging (MRI) monitored targeting photodynamic therapy. In this study, magnetic targeting chitosan nanoparticles (MTCNPs) were prepared and tailored as a drug delivery system and imaging agents for PS, designated as PHPP. Results showed that PHPP-MTCNPs could be used in MRI monitored targeting PDT with excellent targeting and imaging ability. Non-toxicity and high photodynamic efficacy on SW480 carcinoma cells both in vitro and in vivo were achieved with this method at the level of 0-100 μM. Notably, localization of nanoparticles in skin and hepatic tissue was significantly less than in tumor tissue, therefore photosensitivity and hepatotoxicity can be attenuated.

  3. Multifunctional Nanoparticles for Drug Delivery Applications Imaging, Targeting, and Delivery

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    Prud'homme, Robert

    2012-01-01

    This book clearly demonstrates the progression of nanoparticle therapeutics from basic research to applications. Unlike other books covering nanoparticles used in medical applications, Multifunctional Nanoparticles for Drug Delivery Applications presents the medical challenges that can be reduced or even overcome by recent advances in nanoscale drug delivery. Each chapter highlights recent progress in the design and engineering of select multifunctional nanoparticles with topics covering targeting, imaging, delivery, diagnostics, and therapy.

  4. Advances in the Applications of Polyhydroxyalkanoate Nanoparticles for Novel Drug Delivery System

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    Anupama Shrivastav

    2013-01-01

    Full Text Available Drug delivery technology is emerging as an interdisciplinary science aimed at improving human health. The controlled delivery of pharmacologically active agents to the specific site of action at the therapeutically optimal rate and dose regimen has been a major goal in designing drug delivery systems. Over the past few decades, there has been considerable interest in developing biodegradable drug carriers as effective drug delivery systems. Polymeric materials from natural sources play an important role in controlled release of drug at a particular site. Polyhydroxyalkanoates, due to their origin from natural sources, are given attention as candidates for drug delivery materials. Biodegradable and biocompatible polyhydroxyalkanoates are linear polyesters produced by microorganisms under unbalanced growth conditions, which have emerged as potential polymers for use as biomedical materials for drug delivery due to their unique physiochemical and mechanical properties. This review summarizes many of the key findings in the applications of polyhydroxyalkanoates and polyhydroxyalkanoate nanoparticles for drug delivery system.

  5. Protein nanoparticles for therapeutic protein delivery.

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    Herrera Estrada, L P; Champion, J A

    2015-06-01

    Therapeutic proteins can face substantial challenges to their activity, requiring protein modification or use of a delivery vehicle. Nanoparticles can significantly enhance delivery of encapsulated cargo, but traditional small molecule carriers have some limitations in their use for protein delivery. Nanoparticles made from protein have been proposed as alternative carriers and have benefits specific to therapeutic protein delivery. This review describes protein nanoparticles made by self-assembly, including protein cages, protein polymers, and charged or amphipathic peptides, and by desolvation. It presents particle fabrication and delivery characterization for a variety of therapeutic and model proteins, as well as comparison of the features of different protein nanoparticles.

  6. Reductively Responsive Hydrogel Nanoparticles with Uniform Size, Shape, and Tunable Composition for Systemic siRNA Delivery in Vivo.

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    Ma, Da; Tian, Shaomin; Baryza, Jeremy; Luft, J Christopher; DeSimone, Joseph M

    2015-10-05

    To achieve the great potential of siRNA based gene therapy, safe and efficient systemic delivery in vivo is essential. Here we report reductively responsive hydrogel nanoparticles with highly uniform size and shape for systemic siRNA delivery in vivo. "Blank" hydrogel nanoparticles with high aspect ratio were prepared using continuous particle fabrication based on PRINT (particle replication in nonwetting templates). Subsequently, siRNA was conjugated to "blank" nanoparticles via a disulfide linker with a high loading ratio of up to 18 wt %, followed by surface modification to enhance transfection. This fabrication process could be easily scaled up to prepare large quantity of hydrogel nanoparticles. By controlling hydrogel composition, surface modification, and siRNA loading ratio, siRNA conjugated nanoparticles were highly tunable to achieve high transfection efficiency in vitro. FVII-siRNA conjugated nanoparticles were further stabilized with surface coating for in vivo siRNA delivery to liver hepatocytes, and successful gene silencing was demonstrated at both mRNA and protein levels.

  7. Preparing and Characterizing Chitosan Nanoparticles Containing Hemiscorpius lepturus Scorpion Venom as an Antigen Delivery System

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    Mohammadpour Dounighi, N.

    2012-11-01

    Full Text Available In recent years, chitosan nanoparticles have been studied widely for protein delivery. In this study, Hemiscorpius lepturus (HL venom was encapsulated in chitosan nanoparticles. The aim of the present work was to carry out a systematic study for preparing biocompatible and biodegradable nanoparticles for loading HL scorpion venom and to evaluate their potential as an antigen delivery system. In this study, HL venom loaded chitosan nanoparticles fabricated by ionic gelation of chitosan and tripolyphosphate and the factors which may be influenced in the preparation of nanoparticles were analyzed. Also, their physicochemical properties and in vitro release behavior were studied. The optimum encapsulation efficiency and capacity were observed when the chitosan concentration and HL venom were 2mg/ml and 500µg/ml, respectively. The HL venom loaded nanoparticles were in the size range of 130-160nm (polydispersity index values of 0.423 and exhibited the positive zeta potential. Transmission electron microscope imaging showed spherical and smooth surface of nanoparticles. The profiles of the release exhibited a burst releases about 50% in the first 4 hr and then slowed down at a constant rate. The obtained results suggested that the chitosan nanoparticles prepared in this work had the potential for antigen delivery.

  8. Polysaccharides-based polyelectrolyte nanoparticles as protein drugs delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Shu Shujun; Sun Lei; Zhang Xinge, E-mail: zhangxinge@nankai.edu.cn [Nankai University, Key Laboratory of Functional Polymer Materials Ministry of Education, Institute of Polymer Chemistry (China); Wu Zhongming [Tianjin Medical University, Metabolic Diseases Hospital (China); Wang Zhen; Li Chaoxing, E-mail: lcx@nankai.edu.cn [Nankai University, Key Laboratory of Functional Polymer Materials Ministry of Education, Institute of Polymer Chemistry (China)

    2011-09-15

    Polysaccharides-based nanoparticles were prepared by synthesized quaternized chitosan and dextran sulfate through simple ionic-gelation self-assembled method. Introduction of quaternized groups was intended to increase water solubility of chitosan and make the nanoparticles have broader pH sensitive range which can remain more stable in physiological pH and decrease the loss of protein drugs caused by the gastric cavity. The load of BSA was affected by molecular parameter, i.e., degree of substitution, and average molecular weight of quaternized chitosan, as well as concentration of BSA. Fast release occurred in phosphate buffer solution (pH 7.4) while the release was slow in hydrochloric acid (pH 1.4). The drug release mechanism is Fickian diffusion through release kinetics analysis. Cell uptake demonstrated nanoparicles can internalize into Caco-2 cells, which suggested that nanoparticles had good biocompatibility. No significant conformation change was noted for the released BSA in comparison with native BSA using circular dichroism spectroscopy. This kind of novel composite nanoparticles may be a promising delivery system for oral protein and peptide drugs.

  9. Mannosylated Chitosan Nanoparticles Based Macrophage-Targeting Gene Delivery System Enhanced Cellular Uptake and Improved Transfection Efficiency.

    Science.gov (United States)

    Peng, Yixing; Yao, Wenjun; Wang, Bo; Zong, Li

    2015-04-01

    Gene transfer mediated by mannosylated chitosan (MCS) is a safe and promising approach for gene and vaccine delivery. MCS nanoparticles based gene delivery system showed high in vivo delivery efficiency and elicited strong immune responses in mice. However, little knowledge about the cell binding, transfection efficiency and intracellular trafficking of MCS nanoparticles had been acquired. In this study, using gastrin-releasing peptide as a model plasmid (pGRP), the binding of MCS/pGRP nanoparticles to macrophages and the intracellular trafficking of MCS/pGRP nanoparticles in macrophages were investigated. MCS-mediated transfection efficiency in macrophages was also evaluated using pGL-3 as a reporter gene. The results showed that the binding and transfection efficiency of MCS nanoparticles in macrophages was higher than that of CS, which was attributed to the interaction between mannose ligands in MCS and mannose receptors on the surface of macrophages. Observation with a confocal laser scanning microscope indicated the cellular uptake of MCS/pGRP nanoparticles were more than that of CS/pGRP nanoparticles in macrophages. MCS/pGRP nanoparticles were taken up by macrophages and most of them were entrapped in endosomal/lysosomal compartments. After the nanoparticles escaping from endosomal/lysosomal compartments, naked pGRP entered the nucleus, and a few MCS might enter the nucleus in terms of nanoparticles. Overall, MCS has the potential to be an excellent macrophage-targeting gene delivery carrier.

  10. Diatomite silica nanoparticles for drug delivery

    Science.gov (United States)

    Ruggiero, Immacolata; Terracciano, Monica; Martucci, Nicola M.; De Stefano, Luca; Migliaccio, Nunzia; Tatè, Rosarita; Rendina, Ivo; Arcari, Paolo; Lamberti, Annalisa; Rea, Ilaria

    2014-07-01

    Diatomite is a natural fossil material of sedimentary origin, constituted by fragments of diatom siliceous skeletons. In this preliminary work, the properties of diatomite nanoparticles as potential system for the delivery of drugs in cancer cells were exploited. A purification procedure, based on thermal treatments in strong acid solutions, was used to remove inorganic and organic impurities from diatomite and to make them a safe material for medical applications. The micrometric diatomite powder was reduced in nanoparticles by mechanical crushing, sonication, and filtering. Morphological analysis performed by dynamic light scattering and transmission electron microscopy reveals a particles size included between 100 and 300 nm. Diatomite nanoparticles were functionalized by 3-aminopropyltriethoxysilane and labeled by tetramethylrhodamine isothiocyanate. Different concentrations of chemically modified nanoparticles were incubated with cancer cells and confocal microscopy was performed. Imaging analysis showed an efficient cellular uptake and homogeneous distribution of nanoparticles in cytoplasm and nucleus, thus suggesting their potentiality as nanocarriers for drug delivery.

  11. Diatomite silica nanoparticles for drug delivery.

    Science.gov (United States)

    Ruggiero, Immacolata; Terracciano, Monica; Martucci, Nicola M; De Stefano, Luca; Migliaccio, Nunzia; Tatè, Rosarita; Rendina, Ivo; Arcari, Paolo; Lamberti, Annalisa; Rea, Ilaria

    2014-01-01

    Diatomite is a natural fossil material of sedimentary origin, constituted by fragments of diatom siliceous skeletons. In this preliminary work, the properties of diatomite nanoparticles as potential system for the delivery of drugs in cancer cells were exploited. A purification procedure, based on thermal treatments in strong acid solutions, was used to remove inorganic and organic impurities from diatomite and to make them a safe material for medical applications. The micrometric diatomite powder was reduced in nanoparticles by mechanical crushing, sonication, and filtering. Morphological analysis performed by dynamic light scattering and transmission electron microscopy reveals a particles size included between 100 and 300 nm. Diatomite nanoparticles were functionalized by 3-aminopropyltriethoxysilane and labeled by tetramethylrhodamine isothiocyanate. Different concentrations of chemically modified nanoparticles were incubated with cancer cells and confocal microscopy was performed. Imaging analysis showed an efficient cellular uptake and homogeneous distribution of nanoparticles in cytoplasm and nucleus, thus suggesting their potentiality as nanocarriers for drug delivery. 87.85.J81.05.Rm; 61.46. + w.

  12. Overcoming the Challenges of siRNA Delivery: Nanoparticle Strategies.

    Science.gov (United States)

    Shajari, Neda; Mansoori, Behzad; Davudian, Sadaf; Mohammadi, Ali; Baradaran, Behzad

    2017-01-01

    Despite therapeutics based on siRNA have an immense potential for the treatment of incurable diseases such as cancers. However, the in vivo utilization of siRNA and also the delivery of this agent to the target site is one of the most controversial challenges. The helpful assistance by nanoparticles can improve stable delivery and also enhance efficacy. More nanoparticle-based siRNA therapeutics is expected to become available in the near future. The search strategy followed the guidelines of the Centre of Reviews and Dissemination. The studies were identified from seven databases (Scopus, Web of Science, Academic Search Premiere, CINAHL, Medline Ovid, Eric and Cochrane Library). Studies was selected based on titles, abstracts and full texts. One hundred twenty nine papers were included in the review. These papers defined hurdles in RNAi delivery and also strategies to overcome these hurdles. This review discussed the existing hurdles for systemic administration of siRNA as therapeutic agents and highlights the various strategies to overcome these hurdles, including lipid-based nanoparticles and polymeric nanoparticles, and we also briefly reviewed chemical modification. Delivery of siRNA to the target site is the biggest challenge for its application in the clinic. The findings of this review confirmed by encapsulation siRNA in the nanoparticles can overcome these challenges. The rapid progress in nanotechnology has enabled the development of effective nanoparticles as the carrier for siRNA delivery. However, our data about siRNA-based therapeutics and also nanomedicine are still limited. More clinical data needs to be completely understood in the benefits and drawbacks of siRNA-based therapeutics. Prospective studies must pay attention to the in vivo safety profiles of the different delivery systems, including uninvited immune system stimulation and cytotoxicity. In essence, the development of nontoxic, biocompatible, and biodegradable delivery systems for

  13. Biomaterial-Derived Calcium Carbonate Nanoparticles for Enteric Drug Delivery

    Directory of Open Access Journals (Sweden)

    Diane Render

    2016-01-01

    Full Text Available Oral drug delivery systems provide the most convenient, noninvasive, readily acceptable alternatives to parenteral systems. In the current work, eggshell-derived calcium carbonate (CaCO3 nanoparticles were used to develop enteric drug delivery system in the form of tablets. CaCO3 nanoparticles were manufactured using top-down ball-milling method and characterized by X-ray diffractometry (XRD and transmission electron microscopy (TEM and loaded with 5-fluorouracil as a model drug. Tablets with varying CaCO3 core and binder compositions were fabricated and coated with Eudragit S100 or Eudragit L100. Suitability for enteric delivery of the tablets was tested by oral administration to rabbits and radiography. Radiograph images showed that the tablet remained in the stomach of the rabbit for up to 3 hours. Further modifications of these biomaterial-derived nanoparticles and the coatings will enable manufacturing of stable formulations for slow or controlled release of pharmaceuticals for enteric delivery.

  14. PEGylated Silk Nanoparticles for Anticancer Drug Delivery

    DEFF Research Database (Denmark)

    Wongpinyochit, Thidarat; Uhlmann, Petra; Urquhart, Andrew

    2015-01-01

    Silk has a robust clinical track record and is emerging as a promising biopolymer for drug delivery, including its use as nanomedicine. However, silk-based nanomedicines still require further refinements for full exploitation of their potential; the application of “stealth” design principals...... is especially necessary to support their evolution. The aim of this study was to develop and examine the potential of PEGylated silk nanoparticles as an anticancer drug delivery system. We first generated B. mori derived silk nanoparticles by driving β-sheet assembly (size 104 ± 1.7 nm, zeta potential −56 ± 5.......6 mV) using nanoprecipitation. We then surface grafted polyethylene glycol (PEG) to the fabricated silk nanoparticles and verified the aqueous stability and morphology of the resulting PEGylated silk nanoparticles. We assessed the drug loading and release behavior of these nanoparticles using...

  15. The application of drug delivery system about nanoparticles in nuclear medicine

    International Nuclear Information System (INIS)

    Yao Ning; Wang Rongfu

    2013-01-01

    The development of nuclear medicine relies on the advancement of precise probes at the cellular and molecular levels. Nanoparticle as a new molecular probe, is mainly consists of the targeting groups, imaging groups, the superb biocompatible 'shells' and the modify groups. These nanoparticles have the better image contrast by targeting positioning in the target tissues and cells. At the same time, because of the diversity of the materials and the uniqueness of the structures, the nanoparticles can realize multimodal imaging at molecular level, which complement each other's advantages of different imaging modals. If the treatment groups are joined into the nanoparticles, a new nanoparticles are formed-the theranosis nanoparticles, which have realized the diagnosis and therapy at the molecular level synchronously. In addition, the application of intelligent nanoprobes can achieve the smart control of drug release and reduce the side effects of cancer treatment. Anyhow, the development of this new drug delivery system about nanoparticles has brought about a new breakthrough on the nuclear medicine. (authors)

  16. Inhalation method for delivery of nanoparticles to the Drosophila respiratory system for toxicity testing

    International Nuclear Information System (INIS)

    Posgai, Ryan; Ahamed, Maqusood; Hussain, Saber M.; Rowe, John J.; Nielsen, Mark G.

    2009-01-01

    The growth of the nanotechnology industry and subsequent proliferation of nanoparticle types present the need to rapidly assess nanoparticle toxicity. We present a novel, simple and cost-effective nebulizer-based method to deliver nanoparticles to the Drosophila melanogaster respiratory system, for the purpose of toxicity testing. FluoSpheres (registered) , silver, and CdSe/ZnS nanoparticles of different sizes were effectively aerosolized, showing the system is capable of functioning with a wide range of nanoparticle types and sizes. Red fluorescent CdSe/ZnS nanoparticles were successfully delivered to the fly respiratory system, as visualized by fluorescent microscopy. Silver coated and uncoated nanoparticles were delivered in a toxicity test, and induced Hsp70 expression in flies, confirming the utility of this model in toxicity testing. This is the first method developed capable of such delivery, provides the advantage of the Drosophila health model, and can serve as a link between tissue culture and more expensive mammalian models in a tiered toxicity testing strategy.

  17. Inhalation method for delivery of nanoparticles to the Drosophila respiratory system for toxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Posgai, Ryan; Ahamed, Maqusood [Department of Biology, University of Dayton, Dayton, OH, 45469-2320 (United States); Hussain, Saber M. [Applied Biotechnology Branch, Human Effectiveness Directorate Air Force Research Laboratory/RHBP, Wright-Patterson Air Force Base, OH, 45433 (United States); Rowe, John J. [Department of Biology, University of Dayton, Dayton, OH, 45469-2320 (United States); Nielsen, Mark G., E-mail: Mark.Nielsen@notes.udayton.edu [Department of Biology, University of Dayton, Dayton, OH, 45469-2320 (United States)

    2009-12-20

    The growth of the nanotechnology industry and subsequent proliferation of nanoparticle types present the need to rapidly assess nanoparticle toxicity. We present a novel, simple and cost-effective nebulizer-based method to deliver nanoparticles to the Drosophila melanogaster respiratory system, for the purpose of toxicity testing. FluoSpheres (registered) , silver, and CdSe/ZnS nanoparticles of different sizes were effectively aerosolized, showing the system is capable of functioning with a wide range of nanoparticle types and sizes. Red fluorescent CdSe/ZnS nanoparticles were successfully delivered to the fly respiratory system, as visualized by fluorescent microscopy. Silver coated and uncoated nanoparticles were delivered in a toxicity test, and induced Hsp70 expression in flies, confirming the utility of this model in toxicity testing. This is the first method developed capable of such delivery, provides the advantage of the Drosophila health model, and can serve as a link between tissue culture and more expensive mammalian models in a tiered toxicity testing strategy.

  18. Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Warangkana Lohcharoenkal

    2014-01-01

    Full Text Available Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.

  19. Protein nanoparticles as drug delivery carriers for cancer therapy.

    Science.gov (United States)

    Lohcharoenkal, Warangkana; Wang, Liying; Chen, Yi Charlie; Rojanasakul, Yon

    2014-01-01

    Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.

  20. Mucosal delivery of liposome-chitosan nanoparticles complexes

    OpenAIRE

    Carvalho, Edison Samir Mascarelhas; Grenha, Ana; Remuñán-López, Carmen; Alonso, Maria José; Seijo, Begoña

    2009-01-01

    Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can...

  1. Biodegradable PLGA-b-PEG polymeric nanoparticles: synthesis, properties, and nanomedical applications as drug delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Locatelli, Erica; Comes Franchini, Mauro, E-mail: mauro.comesfranchini@unibo.it [University of Bologna, Dipartimento di Chimica Industriale Toso Montanari (Italy)

    2012-12-15

    During the past decades many synthetic polymers have been studied for nanomedicine applications and in particular as drug delivery systems. For this purpose, polymers must be non-toxic, biodegradable, and biocompatible. Polylactic-co-glycolic acid (PLGA) is one of the most studied polymers due to its complete biodegradability and ability to self-assemble into nanometric micelles that are able to entrap small molecules like drugs and to release them into body in a time-dependent manner. Despite fine qualities, using PLGA polymeric nanoparticles for in vivo applications still remains an open challenge due to many factors such as poor stability in water, big diameter (150-200 nm), and the removal of these nanocarriers from the blood stream by the liver and spleen thus reducing the concentration of drugs drastically in tumor tissue. Polyethylene glycol (PEG) is the most used polymers for drug delivery applications and the first PEGylated product is already on the market for over 20 years. This is due to its stealth behavior that inhibits the fast recognition by the immune system (opsonization) and generally leads to a reduced blood clearance of nanocarriers increasing blood circulation time. Furthermore, PEG is hydrophilic and able to stabilize nanoparticles by steric and not ionic effects especially in water. PLGA-PEG block copolymer is an emergent system because it can be easily synthesized and it possesses all good qualities of PLGA and also PEG capability so in the last decade it arose as one of the most promising systems for nanoparticles formation, drug loading, and in vivo drug delivery applications. This review will discuss briefly on PLGA-b-PEG synthesis and physicochemical properties, together with its improved qualities with respect to the single PLGA and PEG polymers. Moreover, we will focus on but in particular will treat nanoparticles formation and uses as new drug delivery system for nanomedical applications.

  2. Systems-level thinking for nanoparticle-mediated therapeutic delivery to neurological diseases.

    Science.gov (United States)

    Curtis, Chad; Zhang, Mengying; Liao, Rick; Wood, Thomas; Nance, Elizabeth

    2017-03-01

    Neurological diseases account for 13% of the global burden of disease. As a result, treating these diseases costs $750 billion a year. Nanotechnology, which consists of small (~1-100 nm) but highly tailorable platforms, can provide significant opportunities for improving therapeutic delivery to the brain. Nanoparticles can increase drug solubility, overcome the blood-brain and brain penetration barriers, and provide timed release of a drug at a site of interest. Many researchers have successfully used nanotechnology to overcome individual barriers to therapeutic delivery to the brain, yet no platform has translated into a standard of care for any neurological disease. The challenge in translating nanotechnology platforms into clinical use for patients with neurological disease necessitates a new approach to: (1) collect information from the fields associated with understanding and treating brain diseases and (2) apply that information using scalable technologies in a clinically-relevant way. This approach requires systems-level thinking to integrate an understanding of biological barriers to therapeutic intervention in the brain with the engineering of nanoparticle material properties to overcome those barriers. To demonstrate how a systems perspective can tackle the challenge of treating neurological diseases using nanotechnology, this review will first present physiological barriers to drug delivery in the brain and common neurological disease hallmarks that influence these barriers. We will then analyze the design of nanotechnology platforms in preclinical in vivo efficacy studies for treatment of neurological disease, and map concepts for the interaction of nanoparticle physicochemical properties and pathophysiological hallmarks in the brain. WIREs Nanomed Nanobiotechnol 2017, 9:e1422. doi: 10.1002/wnan.1422 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  3. Lactoferrin bioconjugated solid lipid nanoparticles: a new drug delivery system for potential brain targeting.

    Science.gov (United States)

    Singh, Indu; Swami, Rajan; Pooja, Deep; Jeengar, Manish Kumar; Khan, Wahid; Sistla, Ramakrishna

    2016-01-01

    Delivery of drugs to brain is a subtle task in the therapy of many severe neurological disorders. Solid lipid nanoparticles (SLN) easily diffuse the blood-brain barrier (BBB) due to their lipophilic nature. Furthermore, ligand conjugation on SLN surface enhances the targeting efficiency. Lactoferin (Lf) conjugated SLN system is first time attempted for effective brain targeting in this study. Preparation of Lf-modified docetaxel (DTX)-loaded SLN for proficient delivery of DTX to brain. DTX-loaded SLN were prepared using emulsification and solvent evaporation method and conjugation of Lf on SLN surface (C-SLN) was attained through carbodiimide chemistry. These lipidic nanoparticles were evaluated by DLS, AFM, FTIR, XRD techniques and in vitro release studies. Colloidal stability study was performed in biologically simulated environment (normal saline and serum). These lipidic nanoparticles were further evaluated for its targeting mechanism for uptake in brain tumour cells and brain via receptor saturation studies and distribution studies in brain, respectively. Particle size of lipidic nanoparticles was found to be optimum. Surface morphology (zeta potential, AFM) and surface chemistry (FTIR) confirmed conjugation of Lf on SLN surface. Cytotoxicity studies revealed augmented apoptotic activity of C-SLN than SLN and DTX. Enhanced cytotoxicity was demonstrated by receptor saturation and uptake studies. Brain concentration of DTX was elevated significantly with C-SLN than marketed formulation. It is evident from the cytotoxicity, uptake that SLN has potential to deliver drug to brain than marketed formulation but conjugating Lf on SLN surface (C-SLN) further increased the targeting potential for brain tumour. Moreover, brain distribution studies corroborated the use of C-SLN as a viable vehicle to target drug to brain. Hence, C-SLN was demonstrated to be a promising DTX delivery system to brain as it possessed remarkable biocompatibility, stability and efficacy than

  4. Nanoparticles and nanofibers for topical drug delivery

    Science.gov (United States)

    Goyal, Ritu; Macri, Lauren K.; Kaplan, Hilton M.; Kohn, Joachim

    2016-01-01

    This review provides the first comprehensive overview of the use of both nanoparticles and nanofibers for topical drug delivery. Researchers have explored the use of nanotechnology, specifically nanoparticles and nanofibers, as drug delivery systems for topical and transdermal applications. This approach employs increased drug concentration in the carrier, in order to increase drug flux into and through the skin. Both nanoparticles and nanofibers can be used to deliver hydrophobic and hydrophilic drugs and are capable of controlled release for a prolonged period of time. The examples presented provide significant evidence that this area of research has—and will continue to have — a profound impact on both clinical outcomes and the development of new products. PMID:26518723

  5. Selenium nanoparticles: potential in cancer gene and drug delivery.

    Science.gov (United States)

    Maiyo, Fiona; Singh, Moganavelli

    2017-05-01

    In recent decades, colloidal selenium nanoparticles have emerged as exceptional selenium species with reported chemopreventative and therapeutic properties. This has sparked widespread interest in their use as a carrier of therapeutic agents with results displaying synergistic effects of selenium with its therapeutic cargo and improved anticancer activity. Functionalization remains a critical step in selenium nanoparticles' development for application in gene or drug delivery. In this review, we highlight recent developments in the synthesis and functionalization strategies of selenium nanoparticles used in cancer drug and gene delivery systems. We also provide an update of recent preclinical studies utilizing selenium nanoparticles in cancer therapeutics.

  6. Polymeric nanoparticles: potent vectors for vaccine delivery targeting cancer and infectious diseases.

    Science.gov (United States)

    Bolhassani, Azam; Javanzad, Shabnam; Saleh, Tayebeh; Hashemi, Mehrdad; Aghasadeghi, Mohammad Reza; Sadat, Seyed Mehdi

    2014-01-01

    Nanocarriers with various compositions and biological properties have been extensively applied for in vitro/in vivo drug and gene delivery. The family of nanocarriers includes polymeric nanoparticles, lipid-based carriers (liposomes/micelles), dendrimers, carbon nanotubes, and gold nanoparticles (nanoshells/nanocages). Among different delivery systems, polymeric carriers have several properties such as: easy to synthesize, inexpensive, biocompatible, biodegradable, non-immunogenic, non-toxic, and water soluble. In addition, cationic polymers seem to produce more stable complexes led to a more protection during cellular trafficking than cationic lipids. Nanoparticles often show significant adjuvant effects in vaccine delivery since they may be easily taken up by antigen presenting cells (APCs). Natural polymers such as polysaccharides and synthetic polymers have demonstrated great potential to form vaccine nanoparticles. The development of new adjuvants or delivery systems for DNA and protein immunization is an expanding research field. This review describes polymeric carriers especially PLGA, chitosan, and PEI as vaccine delivery systems.

  7. Manufacture and Drug Delivery Applications of Silk Nanoparticles.

    Science.gov (United States)

    Wongpinyochit, Thidarat; Johnston, Blair F; Seib, F Philipp

    2016-10-08

    Silk is a promising biopolymer for biomedical and pharmaceutical applications due to its outstanding mechanical properties, biocompatibility and biodegradability, as well its ability to protect and subsequently release its payload in response to a trigger. While silk can be formulated into various material formats, silk nanoparticles are emerging as promising drug delivery systems. Therefore, this article covers the procedures for reverse engineering silk cocoons to yield a regenerated silk solution that can be used to generate stable silk nanoparticles. These nanoparticles are subsequently characterized, drug loaded and explored as a potential anticancer drug delivery system. Briefly, silk cocoons are reverse engineered first by degumming the cocoons, followed by silk dissolution and clean up, to yield an aqueous silk solution. Next, the regenerated silk solution is subjected to nanoprecipitation to yield silk nanoparticles - a simple but powerful method that generates uniform nanoparticles. The silk nanoparticles are characterized according to their size, zeta potential, morphology and stability in aqueous media, as well as their ability to entrap a chemotherapeutic payload and kill human breast cancer cells. Overall, the described methodology yields uniform silk nanoparticles that can be readily explored for a myriad of applications, including their use as a potential nanomedicine.

  8. Drug Delivery Nanoparticles in Skin Cancers

    Science.gov (United States)

    Dianzani, Chiara; Zara, Gian Paolo; Maina, Giovanni; Pettazzoni, Piergiorgio; Pizzimenti, Stefania; Rossi, Federica; Gigliotti, Casimiro Luca; Ciamporcero, Eric Stefano; Daga, Martina; Barrera, Giuseppina

    2014-01-01

    Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported. PMID:25101298

  9. Nanoparticle functionalization for brain targeting drug delivery and diagnostic

    DEFF Research Database (Denmark)

    Gomes, Maria João; Mendes, Bárbara; Martins, Susana

    2016-01-01

    carriers to cross the BBB and achieve brain, and their functionalization strategies are described; and finally the delivery of nanoparticles to the target moiety, as diagnostics or therapeutics. Therefore, this chapter is focused on how the nanoparticle surface may be functionalized for drug delivery......Nanobiotechnology has been demonstrated to be an efficient tool for targeted therapy as well as diagnosis, with particular emphasis on brain tumor and neurodegenerative diseases. On this regard, the aim of this chapter is focused on engineered nanoparticles targeted to the brain, so that they have...... and diagnostics. Furthermore, it is also mentioned that some BBB targets were already used as transport mediators to central nervous system by functionalization on nanoparticles. It summarizes the nanoparticles potential in therapeutics and molecular targeting to BBB, and also an approach of the nanoparticle...

  10. Development of a real time imaging-based guidance system of magnetic nanoparticles for targeted drug delivery

    International Nuclear Information System (INIS)

    Zhang, Xingming; Le, Tuan-Anh; Yoon, Jungwon

    2017-01-01

    Targeted drug delivery using magnetic nanoparticles is an efficient technique as molecules can be directed toward specific tissues inside a human body. For the first time, we implemented a real-time imaging-based guidance system of nanoparticles using untethered electro-magnetic devices for simultaneous guiding and tracking. In this paper a low-amplitude-excitation-field magnetic particle imaging (MPI) is introduced. Based on this imaging technology, a hybrid system comprised of an electromagnetic actuator and MPI was used to navigate nanoparticles in a non-invasive way. The real-time low-amplitude-excitation-field MPI and electromagnetic actuator of this navigation system are achieved by applying a time-division multiplexing scheme to the coil topology. A one dimensional nanoparticle navigation system was built to demonstrate the feasibility of the proposed approach and it could achieve a 2 Hz navigation update rate with the field gradient of 3.5 T/m during the imaging mode and 8.75 T/m during the actuation mode. Particles with both 90 nm and 5 nm diameters could be successfully manipulated and monitored in a tube through the proposed system, which can significantly enhance targeting efficiency and allow precise analysis in a real drug delivery. - Highlights: • A real-time system comprised of an electromagnetic actuator and a low-amplitude-excitation-field MPI can navigate magnetic nanoparticles. • The imaging scheme is feasible to enlarge field of view size. • The proposed navigation system can be cost efficient, compact, and optimized for targeting of the nanoparticles.

  11. Development of a real time imaging-based guidance system of magnetic nanoparticles for targeted drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xingming [School of Naval Architecture and Ocean Engineering, Harbin Institute of Technology at Weihai, Weihai, Shandong (China); School of Mechanical and Aerospace Engineering & ReCAPT, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Le, Tuan-Anh [School of Mechanical and Aerospace Engineering & ReCAPT, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Yoon, Jungwon, E-mail: jwyoon@gnu.ac.kr [School of Mechanical and Aerospace Engineering & ReCAPT, Gyeongsang National University, Jinju 660-701 (Korea, Republic of)

    2017-04-01

    Targeted drug delivery using magnetic nanoparticles is an efficient technique as molecules can be directed toward specific tissues inside a human body. For the first time, we implemented a real-time imaging-based guidance system of nanoparticles using untethered electro-magnetic devices for simultaneous guiding and tracking. In this paper a low-amplitude-excitation-field magnetic particle imaging (MPI) is introduced. Based on this imaging technology, a hybrid system comprised of an electromagnetic actuator and MPI was used to navigate nanoparticles in a non-invasive way. The real-time low-amplitude-excitation-field MPI and electromagnetic actuator of this navigation system are achieved by applying a time-division multiplexing scheme to the coil topology. A one dimensional nanoparticle navigation system was built to demonstrate the feasibility of the proposed approach and it could achieve a 2 Hz navigation update rate with the field gradient of 3.5 T/m during the imaging mode and 8.75 T/m during the actuation mode. Particles with both 90 nm and 5 nm diameters could be successfully manipulated and monitored in a tube through the proposed system, which can significantly enhance targeting efficiency and allow precise analysis in a real drug delivery. - Highlights: • A real-time system comprised of an electromagnetic actuator and a low-amplitude-excitation-field MPI can navigate magnetic nanoparticles. • The imaging scheme is feasible to enlarge field of view size. • The proposed navigation system can be cost efficient, compact, and optimized for targeting of the nanoparticles.

  12. PEGylated Silk Nanoparticles for Anticancer Drug Delivery.

    Science.gov (United States)

    Wongpinyochit, Thidarat; Uhlmann, Petra; Urquhart, Andrew J; Seib, F Philipp

    2015-11-09

    Silk has a robust clinical track record and is emerging as a promising biopolymer for drug delivery, including its use as nanomedicine. However, silk-based nanomedicines still require further refinements for full exploitation of their potential; the application of "stealth" design principals is especially necessary to support their evolution. The aim of this study was to develop and examine the potential of PEGylated silk nanoparticles as an anticancer drug delivery system. We first generated B. mori derived silk nanoparticles by driving β-sheet assembly (size 104 ± 1.7 nm, zeta potential -56 ± 5.6 mV) using nanoprecipitation. We then surface grafted polyethylene glycol (PEG) to the fabricated silk nanoparticles and verified the aqueous stability and morphology of the resulting PEGylated silk nanoparticles. We assessed the drug loading and release behavior of these nanoparticles using clinically established and emerging anticancer drugs. Overall, PEGylated silk nanoparticles showed high encapsulation efficiency (>93%) and a pH-dependent release over 14 days. Finally, we demonstrated significant cytotoxicity of drug loaded silk nanoparticles applied as single and combination nanomedicines to human breast cancer cells. In conclusion, these results, taken together with prior silk nanoparticle data, support a viable future for silk-based nanomedicines.

  13. In vivo studies of transdermal nanoparticle delivery with microneedles using photoacoustic microscopy

    Science.gov (United States)

    Moothanchery, Mohesh; Seeni, Razina Z.; Xu, Chenjie; Pramanik, Manojit

    2017-01-01

    Microneedle technology allows micron-sized conduits to be formed within the outermost skin layers for both localized and systemic delivery of therapeutics including nanoparticles. Histological methods are often employed for characterization, and unfortunately do not allow for the in vivo visualization of the delivery process. This study presents the utilization of optical resolution-photoacoustic microscopy to characterize the transdermal delivery of nanoparticles using microneedles. Specifically, we observe the in vivo transdermal delivery of gold nanoparticles using microneedles in mice ear and study the penetration, diffusion, and spatial distribution of the nanoparticles in the tissue. The promising results reveal that photoacoustic microscopy can be used as a potential imaging modality for the in vivo characterization of microneedles based drug delivery. PMID:29296482

  14. Surfactant-assisted sol–gel synthesis of forsterite nanoparticles as a novel drug delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Hassanzadeh-Tabrizi, S.A., E-mail: tabrizi1980@gmail.com [Young Researchers and Elite Club, Najafabad Branch, Islamic Azad University, Najafabad, Isfahan (Iran, Islamic Republic of); Bigham, Ashkan [Advanced Materials Research Center, Materials Engineering Department, Najafabad Branch, Islamic Azad University, Najafabad, Isfahan (Iran, Islamic Republic of); Rafienia, Mohammad [Biosensor Research Center, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of)

    2016-01-01

    In the present study, forsterite nanoparticles were synthesized via surfactant-assisted sol–gel method using cetyltrimethyl ammonium bromide (CTAB) as a surfactant. The effects of CTAB contents and heat treatment on the textural properties and drug release from nanoparticles were investigated. The synthesized powders were studied by X-ray diffraction, Fourier transform infrared spectra, Brunauer–Emmett–Teller surface area analysis and transmission electron microscope images. Mg{sub 2}SiO{sub 4} materials demonstrated mesoporous characteristics and large specific surface area ranging from 159 to 30 m{sup 2}/g. The TEM results showed that forsterite nanorods had diameters about 4 nm and lengths ranging from 10 to 60 nm. It was found that the samples with 6 g CTAB show slower drug release rate than the other specimens, which is due to smaller pore size. This study revealed that the drug delivery of forsterite can be tailored by changing the amount of surfactant. - Highlights: • Forsterite nanoparticles were synthesized via surfactant-assisted sol–gel method. • Nanoparticles were loaded with ibuprofen as a novel drug delivery system. • Synthesized nanoparticles had a rod-like morphology. • CTAB concentration strongly affected the textural properties and drug release of the nanoparticles.

  15. Preparation of magnetic nanoparticles and their application to magnetic targeting drug delivery

    International Nuclear Information System (INIS)

    Li Guiping; Wang Yongxian

    2006-01-01

    Magnetic nanoparticles barrier is a novel kind of drug delivery system for magnetic targeting drugs, which can effectively deliver the drug to a tumor target site and increase therapeutic benefit, with the side effects minimized. This article summarizes the most outstanding papers on the of magnetic nanoparticles used as the targeting drug's delivery systems. (authors)

  16. Fluoride loaded polymeric nanoparticles for dental delivery.

    Science.gov (United States)

    Nguyen, Sanko; Escudero, Carlos; Sediqi, Nadia; Smistad, Gro; Hiorth, Marianne

    2017-06-15

    The overall aim of the present paper was to develop fluoride loaded nanoparticles based on the biopolymers chitosan, pectin, and alginate, for use in dental delivery. First, the preparation of nanoparticles in the presence of sodium fluoride (NaF) as the active ingredient by ionic gelation was investigated followed by an evaluation of their drug entrapment and release properties. Chitosan formed stable, spherical, and monodisperse nanoparticles in the presence of NaF and tripolyphoshate as the crosslinker, whereas alginate and pectin were not able to form any definite nanostructures in similar conditions. The fluoride loading capacity was found to be 33-113ppm, and the entrapment efficiency 3.6-6.2% for chitosan nanoparticles prepared in 0.2-0.4% (w/w) NaF, respectively. A steady increase in the fluoride release was observed for chitosan nanoparticles prepared in 0.2% NaF both in pH5 and 7 until it reached a maximum at time point 4h and maintained at this level for at least 24h. Similar profiles were observed for formulations prepared in 0.4% NaF; however the fluoride was released at a higher level at pH5. The low concentration, but continuous delivery of fluoride from the chitosan nanoparticles, with possible expedited release in acidic environment, makes these formulations highly promising as dental delivery systems in the protection against caries development. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Generic Delivery of Payload of Nanoparticles Intracellularly via Hybrid Polymer Capsules for Bioimaging Applications

    Science.gov (United States)

    Sami, Haider; Maparu, Auhin K.; Kumar, Ashok; Sivakumar, Sri

    2012-01-01

    Towards the goal of development of a generic nanomaterial delivery system and delivery of the ‘as prepared’ nanoparticles without ‘further surface modification’ in a generic way, we have fabricated a hybrid polymer capsule as a delivery vehicle in which nanoparticles are loaded within their cavity. To this end, a generic approach to prepare nanomaterials-loaded polyelectrolyte multilayered (PEM) capsules has been reported, where polystyrene sulfonate (PSS)/polyallylamine hydrochloride (PAH) polymer capsules were employed as nano/microreactors to synthesize variety of nanomaterials (metal nanoparticles; lanthanide doped inorganic nanoparticles; gadolinium based nanoparticles, cadmium based nanoparticles; different shapes of nanoparticles; co-loading of two types of nanoparticles) in their hollow cavity. These nanoparticles-loaded capsules were employed to demonstrate generic delivery of payload of nanoparticles intracellularly (HeLa cells), without the need of individual nanoparticle surface modification. Validation of intracellular internalization of nanoparticles-loaded capsules by HeLa cells was ascertained by confocal laser scanning microscopy. The green emission from Tb3+ was observed after internalization of LaF3:Tb3+(5%) nanoparticles-loaded capsules by HeLa cells, which suggests that nanoparticles in hybrid capsules retain their functionality within the cells. In vitro cytotoxicity studies of these nanoparticles-loaded capsules showed less/no cytotoxicity in comparison to blank capsules or untreated cells, thus offering a way of evading direct contact of nanoparticles with cells because of the presence of biocompatible polymeric shell of capsules. The proposed hybrid delivery system can be potentially developed to avoid a series of biological barriers and deliver multiple cargoes (both simultaneous and individual delivery) without the need of individual cargo design/modification. PMID:22649489

  18. Generic delivery of payload of nanoparticles intracellularly via hybrid polymer capsules for bioimaging applications.

    Directory of Open Access Journals (Sweden)

    Haider Sami

    Full Text Available Towards the goal of development of a generic nanomaterial delivery system and delivery of the 'as prepared' nanoparticles without 'further surface modification' in a generic way, we have fabricated a hybrid polymer capsule as a delivery vehicle in which nanoparticles are loaded within their cavity. To this end, a generic approach to prepare nanomaterials-loaded polyelectrolyte multilayered (PEM capsules has been reported, where polystyrene sulfonate (PSS/polyallylamine hydrochloride (PAH polymer capsules were employed as nano/microreactors to synthesize variety of nanomaterials (metal nanoparticles; lanthanide doped inorganic nanoparticles; gadolinium based nanoparticles, cadmium based nanoparticles; different shapes of nanoparticles; co-loading of two types of nanoparticles in their hollow cavity. These nanoparticles-loaded capsules were employed to demonstrate generic delivery of payload of nanoparticles intracellularly (HeLa cells, without the need of individual nanoparticle surface modification. Validation of intracellular internalization of nanoparticles-loaded capsules by HeLa cells was ascertained by confocal laser scanning microscopy. The green emission from Tb(3+ was observed after internalization of LaF(3:Tb(3+(5% nanoparticles-loaded capsules by HeLa cells, which suggests that nanoparticles in hybrid capsules retain their functionality within the cells. In vitro cytotoxicity studies of these nanoparticles-loaded capsules showed less/no cytotoxicity in comparison to blank capsules or untreated cells, thus offering a way of evading direct contact of nanoparticles with cells because of the presence of biocompatible polymeric shell of capsules. The proposed hybrid delivery system can be potentially developed to avoid a series of biological barriers and deliver multiple cargoes (both simultaneous and individual delivery without the need of individual cargo design/modification.

  19. Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer via p53/PRC1 pathway.

    Science.gov (United States)

    Ye, Bai-Liang; Zheng, Ru; Ruan, Xiao-Jiao; Zheng, Zhi-Hai; Cai, Hua-Jie

    2018-01-01

    Nano-particles have been widely used in target-specific drug delivery system and showed advantages in cancers treatment. This study aims to evaluate the effect of chitosan coated doxorubicin nano-particles drug delivery system in liver cancer. The chitosan nano-particles were prepared by using the ionic gelation method. The characterizations of the nano-particles were determined by transmission electron microscopy. The cytotoxicity was detected by MTT assay, and the endocytosis, cell apoptosis and cell cycle were examined by flow cytometry. The protein level was analyzed with western blot. The dual luciferase reporter assay was performed to assess the interaction between p53 and the promoter of PRC1, and chromatin immune-precipitation was used to verify the binding between them. The FA-CS-DOX nano-particles were irregular and spherical particles around 30-40 nm, with uniform size and no adhesion. No significant difference was noted in doxorubicin release rate between CS-DOX and FA-CS-DOX. FA-CS-DOX nano-particles showed stronger cytotoxicity than CS-DOX. FA-CS-DOX nano-particles promoted the apoptosis and arrested cell cycle at G2/M phase, and they up-regulated p53. FA-CS-DOX nano-particles inhibited cell survival through p53/PRC1 pathway. Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer by promoting apoptosis and arresting cell cycle at G2/M phase through p53/PRC1 pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Layered double hydroxide nanoparticles in gene and drug delivery.

    Science.gov (United States)

    Ladewig, Katharina; Xu, Zhi Ping; Lu, Gao Qing Max

    2009-09-01

    Layered double hydroxides (LDHs) have been known for many decades as catalyst and ceramic precursors, traps for anionic pollutants, catalysts and additives for polymers, but their successful synthesis on the nanometer scale a few years ago opened up a whole new field for their application in nanomedicine. The delivery of drugs and other therapeutic/bioactive molecules (e.g., peptides, proteins, nucleic acids) to mammalian cells is an area of research that is of tremendous importance to medicine and provides manifold applications for any new developments in the area of nanotechnology. Among the many different nanoparticles that have been shown to facilitate gene and/or drug delivery, LDH nanoparticles have attracted particular attention owing to their many desirable properties. This review aims to report recent progress in gene and drug delivery using LDH nanoparticles. It summarizes the advantages and disadvantages of using LDH nanoparticles as carriers for nucleic acids and drugs against the general background of bottlenecks that are encountered by cellular delivery systems. It describes further the models that have been proposed for the internalization of LDH nanoparticles into cells so far and discusses the intracellular fate of the particles and their cargo. The authors offer some remarks on how this field of research will progress in the near future and which challenges need to be overcome before LDH nanoparticles can be used in a clinical setting.

  1. A comparative study on the nanoparticles for improved drug delivery systems.

    Science.gov (United States)

    Mahmoodi, Nosrat O; Ghavidast, Atefeh; Amirmahani, Najmeh

    2016-09-01

    Nanoparticles have attracted considerable recent interest for diverse biomedical applications because of the unique properties of the nanomaterials. It is already known that one of the major advances in the relative application of nanoparticles is the recognition of the steric stabilization which can increase the particle stability in the biological environment and provide the opportunities of the application of nanoparticles in the development of drug delivery systems (DDSs) for achieving drug targeting and controlled drug release. To facilitate their use in such applications, the appropriate design of surface ligands on these nanoparticles is necessary. In view of these, functionalized nanoparticles through surface modification can be utilized to specifically interact with the target molecules on the cell membrane or intracellular ones. This review briefly presents self-assembled nanoparticles with molecules of therapeutic significance with two strategies. The first strategy attempts to improve the placement of the drugs using conjugating the appropriate ligands or adding targeting moieties to the DDS. The second strategy utilizes trigger-controlled drug-release, which restricts drug release at the targeted site to kill cancer cells by externally controlled mechanisms. Among external stimulations, conveniently light has attracted much interest because it, as an orthogonal external stimulus, gives spatiotemporal control of payload release. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Bio-inspired engineering of cell- and virus-like nanoparticles for drug delivery.

    Science.gov (United States)

    Parodi, Alessandro; Molinaro, Roberto; Sushnitha, Manuela; Evangelopoulos, Michael; Martinez, Jonathan O; Arrighetti, Noemi; Corbo, Claudia; Tasciotti, Ennio

    2017-12-01

    The engineering of future generations of nanodelivery systems aims at the creation of multifunctional vectors endowed with improved circulation, enhanced targeting and responsiveness to the biological environment. Moving past purely bio-inert systems, researchers have begun to create nanoparticles capable of proactively interacting with the biology of the body. Nature offers a wide-range of sources of inspiration for the synthesis of more effective drug delivery platforms. Because the nano-bio-interface is the key driver of nanoparticle behavior and function, the modification of nanoparticles' surfaces allows the transfer of biological properties to synthetic carriers by imparting them with a biological identity. Modulation of these surface characteristics governs nanoparticle interactions with the biological barriers they encounter. Building off these observations, we provide here an overview of virus- and cell-derived biomimetic delivery systems that combine the intrinsic hallmarks of biological membranes with the delivery capabilities of synthetic carriers. We describe the features and properties of biomimetic delivery systems, recapitulating the distinctive traits and functions of viruses, exosomes, platelets, red and white blood cells. By mimicking these biological entities, we will learn how to more efficiently interact with the human body and refine our ability to negotiate with the biological barriers that impair the therapeutic efficacy of nanoparticles. Copyright © 2017. Published by Elsevier Ltd.

  3. Drug delivery with topically applied nanoparticles: science fiction or reality.

    Science.gov (United States)

    Lademann, J; Richter, H; Meinke, M C; Lange-Asschenfeldt, B; Antoniou, C; Mak, W C; Renneberg, R; Sterry, W; Patzelt, A

    2013-01-01

    The efficacy of topically applied drugs is determined by their action mechanism and their potential capacity of passing the skin barrier. Nanoparticles are assumed to be efficient carrier systems for drug delivery through the skin barrier. For flexible nanoparticles like liposomes, this effect has been well demonstrated. The penetration properties of solid nanoparticles are currently under intensive investigation. The crucial advantage of nanoparticles over non-particulate substances is their capability to penetrate deeply into the hair follicles where they can be stored for several days. There is no evidence, yet, that solid particles ≥40 nm are capable of passing through the healthy skin barrier. Therefore and in spite of the long-standing research efforts in this field, commercially available solid nanoparticle-based products for drug delivery through the healthy skin are still missing. Nevertheless, the prospects for the clinical use of nanoparticles in drug delivery are tremendous. They can be designed as transport systems delivering drugs efficiently into the hair follicles in the vicinity of specific target structures. Once deposited at these structures, specific signals might trigger the release of the drugs and exert their effects on the target cells. In this article, examples of such triggered drug release are presented. © 2013 S. Karger AG, Basel.

  4. Diphtheria toxoid loaded poly-(epsilon-caprolactone) nanoparticles as mucosal vaccine delivery systems.

    Science.gov (United States)

    Singh, Jasvinder; Pandit, Sreenivas; Bramwell, Vincent W; Alpar, H Oya

    2006-02-01

    Poly-(epsilon-caprolactone) (PCL), a poly(lactide-co-glycolide) (PLGA)-PCL blend and co-polymer nanoparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. The nanoparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method, demonstrated release profiles which were dependent on the properties of the polymers. An in vitro experiment using Caco-2 cells showed significantly higher uptake of PCL nanoparticles in comparison to polymeric PLGA, the PLGA-PCL blend and co-polymer nanoparticles. The highest uptake mediated by the most hydrophobic nanoparticles using Caco-2 cells was mirrored in the in vivo studies following nasal administration. PCL nanoparticles induced DT serum specific IgG antibody responses significantly higher than PLGA. A significant positive correlation between hydrophobicity of the nanoparticles and the immune response was observed following intramuscular administration. The positive correlation between hydrophobicity of the nanoparticles and serum DT specific IgG antibody response was also observed after intranasal administration of the nanoparticles. The cytokine assays showed that the serum IgG antibody response induced is different according to the route of administration, indicated by the differential levels of IL-6 and IFN-gamma. The nanoparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-6 and IFN-gamma.

  5. System with embedded drug release and nanoparticle degradation sensor showing efficient rifampicin delivery into macrophages.

    Science.gov (United States)

    Trousil, Jiří; Filippov, Sergey K; Hrubý, Martin; Mazel, Tomáš; Syrová, Zdeňka; Cmarko, Dušan; Svidenská, Silvie; Matějková, Jana; Kováčik, Lubomír; Porsch, Bedřich; Konefał, Rafał; Lund, Reidar; Nyström, Bo; Raška, Ivan; Štěpánek, Petr

    2017-01-01

    We have developed a biodegradable, biocompatible system for the delivery of the antituberculotic antibiotic rifampicin with a built-in drug release and nanoparticle degradation fluorescence sensor. Polymer nanoparticles based on poly(ethylene oxide) monomethyl ether-block-poly(ε-caprolactone) were noncovalently loaded with rifampicin, a combination that, to best of our knowledge, was not previously described in the literature, which showed significant benefits. The nanoparticles contain a Förster resonance energy transfer (FRET) system that allows real-time assessment of drug release not only in vitro, but also in living macrophages where the mycobacteria typically reside as hard-to-kill intracellular parasites. The fluorophore also enables in situ monitoring of the enzymatic nanoparticle degradation in the macrophages. We show that the nanoparticles are efficiently taken up by macrophages, where they are very quickly associated with the lysosomal compartment. After drug release, the nanoparticles in the cmacrophages are enzymatically degraded, with half-life 88±11 min. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery

    Directory of Open Access Journals (Sweden)

    Ji Young Yhee

    2016-09-01

    Full Text Available Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD, cystic fibrosis (CF, idiopathic pulmonary fibrosis (IPF, and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed.

  7. Hybrid protein-synthetic polymer nanoparticles for drug delivery.

    Science.gov (United States)

    Koseva, Neli S; Rydz, Joanna; Stoyanova, Ekaterina V; Mitova, Violeta A

    2015-01-01

    Among the most common nanoparticulate systems, the polymeric nanocarriers have a number of key benefits, which give a great choice of delivery platforms. Nevertheless, polymeric nanoparticles possess some limitations that include use of toxic solvents in the production process, polymer degradation, drug leakage outside the diseased tissue, and polymer cytotoxicity. The combination of polymers of biological and synthetic origin is an appealing modern strategy for the production of novel nanocarriers with unprecedented properties. Proteins' interface can play an important role in determining bioactivity and toxicity and gives perspective for future development of the polymer-based nanoparticles. The design of hybrid constructs composed of synthetic polymer and biological molecules such as proteins can be considered as a straightforward tool to integrate a broad spectrum of properties and biofunctions into a single device. This review discusses hybrid protein-synthetic polymer nanoparticles with different structures and levels in complexity and functionality, in view of their applications as drug delivery systems. © 2015 Elsevier Inc. All rights reserved.

  8. Advances in the synthesis and application of nanoparticles for drug delivery.

    Science.gov (United States)

    Park, Wooram; Na, Kun

    2015-01-01

    The continuous development of drug delivery systems (DDSs) has been extensively researched by the need to maximize therapeutic efficacy while minimizing undesirable side effects. Nanoparticle technology was recently shown to hold great promise for drug delivery applications in nanomedicine due to its beneficial properties, such as better encapsulation, bioavailability, control release, and lower toxic effect. Despite the great progress in nanomedicine, there remain many limitations for clinical application. To overcome these limitations, advanced nanoparticles for drug delivery have been developed to enable the spatially and temporally controlled release of drugs in response to specific stimuli at disease sites. Furthermore, the controlled self-assembly of organic and inorganic materials may enable their use in theranostic applications. This review presents an overview of a recent advanced nanoparticulate system that can be used as a potential drug delivery carrier and focuses on the potential applications of nanoparticles in various biomedical fields for human health care. © 2015 Wiley Periodicals, Inc.

  9. Photo-synthesis of protein-based nanoparticles and the application in drug delivery

    International Nuclear Information System (INIS)

    Xie, Jinbing; Wang, Hongyang; Cao, Yi; Qin, Meng; Wang, Wei

    2015-01-01

    Recently, protein-based nanoparticles as drug delivery systems have attracted great interests due to the excellent behavior of high biocompatibility and biodegradability, and low toxicity. However, the synthesis techniques are generally costly, chemical reagents introduced, and especially present difficulties in producing homogeneous monodispersed nanoparticles. Here, we introduce a novel physical method to synthesize protein nanoparticles which can be accomplished under physiological condition only through ultraviolet (UV) illumination. By accurately adjusting the intensity and illumination time of UV light, disulfide bonds in proteins can be selectively reduced and the subsequent self-assembly process can be well controlled. Importantly, the co-assembly can also be dominated when the proteins mixed with either anti-cancer drugs, siRNA, or active targeting molecules. Both in vitro and in vivo experiments indicate that our synthesized protein–drug nanoparticles (drug-loading content and encapsulation efficiency being ca. 8.2% and 70%, respectively) not only possess the capability of traditional drug delivery systems (DDS), but also have a greater drug delivery efficiency to the tumor sites and a better inhibition of tumor growth (only 35% of volume comparing to the natural growing state), indicating it being a novel drug delivery system in tumor therapy

  10. Nanoparticle enabled transdermal drug delivery systems for enhanced dose control and tissue targeting

    Science.gov (United States)

    Palmer, Brian C.; DeLouise, Lisa A.

    2017-01-01

    Transdermal drug delivery systems have been around for decades, and current technologies (e.g. patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases. PMID:27983701

  11. Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting.

    Science.gov (United States)

    Palmer, Brian C; DeLouise, Lisa A

    2016-12-15

    Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

  12. A facile construction strategy of stable lipid nanoparticles for drug delivery using a hydrogel-thickened microemulsion system

    Science.gov (United States)

    Chen, Huabing; Xiao, Ling; Du, Danrong; Mou, Dongsheng; Xu, Huibi; Yang, Xiangliang

    2010-01-01

    We report a novel facile method for preparing stable nanoparticles with inner spherical solid spheres and an outer hydrogel matrix using a hot O/W hydrogel-thickened microemulsion with spontaneous stability. The nanoparticles with average diameters of about 30.0 nm and 100.0 nm were constructed by cooling the hot hydrogel-thickened microemulsion at different temperatures, respectively. We explained the application of these nanoparticles by actualizing the cutaneous delivery of drug-loaded nanoparticles. The in vitro skin permeation studies showed that the nanoparticles could significantly reduce the penetration of model drugs through skin and resulted in their dermal uptakes in skin. The sol-gel process of TEOS was furthermore used in the template of HTM to regulate the particle size of nanoparticles. The coating of silica on the surface of nanoparticles could regulate the penetration of drug into skin from dermal delivery to transdermal delivery. This strategy provides a facile method to produce nanoparticles with long-term stability and ease of manufacture, which might have a promising application in drug delivery.

  13. Concanavalin A conjugated biodegradable nanoparticles for oral insulin delivery

    Science.gov (United States)

    Hurkat, Pooja; Jain, Aviral; Jain, Ashish; Shilpi, Satish; Gulbake, Arvind; Jain, Sanjay K.

    2012-11-01

    Major research issues in oral protein delivery include the stabilization of protein in delivery devices which could increase its oral bioavailability. The study deals with development of oral insulin delivery system utilizing biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and modifying its surface with Concanavalin A to increase lymphatic uptake. Surface-modified PLGA nanoparticles were characterized for conjugation efficiency of ligand, shape and surface morphology, particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro drug release. Stability of insulin in the developed formulation was confirmed by SDS-PAGE, and integrity of entrapped insulin was assessed using circular dichroism spectrum. Ex vivo study was performed on Wistar rats, which exhibited the higher intestinal uptake of Con A conjugated nanoparticles. In vivo study performed on streptozotocin-induced diabetic rats which indicate that a surface-modified nanoparticle reduces blood glucose level effectively within 4 h of its oral administration. In conclusion, the present work resulted in successful production of Con A NPs bearing insulin with sustained release profile, and better absorption and stability. The Con A NPs showed high insulin uptake, due to its relative high affinity for non-reducing carbohydrate residues i.e., fucose present on M cells and have the potential for oral insulin delivery in effective management of Type 1 diabetes condition.

  14. Concanavalin A conjugated biodegradable nanoparticles for oral insulin delivery

    Energy Technology Data Exchange (ETDEWEB)

    Hurkat, Pooja; Jain, Aviral; Jain, Ashish; Shilpi, Satish; Gulbake, Arvind; Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour Vishwavidyalaya, Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2012-11-15

    Major research issues in oral protein delivery include the stabilization of protein in delivery devices which could increase its oral bioavailability. The study deals with development of oral insulin delivery system utilizing biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and modifying its surface with Concanavalin A to increase lymphatic uptake. Surface-modified PLGA nanoparticles were characterized for conjugation efficiency of ligand, shape and surface morphology, particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro drug release. Stability of insulin in the developed formulation was confirmed by SDS-PAGE, and integrity of entrapped insulin was assessed using circular dichroism spectrum. Ex vivo study was performed on Wistar rats, which exhibited the higher intestinal uptake of Con A conjugated nanoparticles. In vivo study performed on streptozotocin-induced diabetic rats which indicate that a surface-modified nanoparticle reduces blood glucose level effectively within 4 h of its oral administration. In conclusion, the present work resulted in successful production of Con A NPs bearing insulin with sustained release profile, and better absorption and stability. The Con A NPs showed high insulin uptake, due to its relative high affinity for non-reducing carbohydrate residues i.e., fucose present on M cells and have the potential for oral insulin delivery in effective management of Type 1 diabetes condition.

  15. Increased Loading, Efficacy and Sustained Release of Silibinin, a Poorly Soluble Drug Using Hydrophobically-Modified Chitosan Nanoparticles for Enhanced Delivery of Anticancer Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Cha Yee Kuen

    2017-11-01

    Full Text Available Conventional delivery of anticancer drugs is less effective due to pharmacological drawbacks such as lack of aqueous solubility and poor cellular accumulation. This study reports the increased drug loading, therapeutic delivery, and cellular accumulation of silibinin (SLB, a poorly water-soluble phenolic compound using a hydrophobically-modified chitosan nanoparticle (pCNP system. In this study, chitosan nanoparticles were hydrophobically-modified to confer a palmitoyl group as confirmed by 2,4,6-Trinitrobenzenesulfonic acid (TNBS assay. Physicochemical features of the nanoparticles were studied using the TNBS assay, and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR analyses. The FTIR profile and electron microscopy correlated the successful formation of pCNP and pCNP-SLB as nano-sized particles, while Dynamic Light Scattering (DLS and Field Emission-Scanning Electron Microscopy (FESEM results exhibited an expansion in size between pCNP and pCNP-SLB to accommodate the drug within its particle core. To evaluate the cytotoxicity of the nanoparticles, a Methylthiazolyldiphenyl-tetrazolium bromide (MTT cytotoxicity assay was subsequently performed using the A549 lung cancer cell line. Cytotoxicity assays exhibited an enhanced efficacy of SLB when delivered by CNP and pCNP. Interestingly, controlled release delivery of SLB was achieved using the pCNP-SLB system, conferring higher cytotoxic effects and lower IC50 values in 72-h treatments compared to CNP-SLB, which was attributed to the hydrophobic modification of the CNP system.

  16. Solid lipid nanoparticles as oral delivery systems of phenolic compounds: Overcoming pharmacokinetic limitations for nutraceutical applications.

    Science.gov (United States)

    Nunes, Sara; Madureira, Ana Raquel; Campos, Débora; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Manuela; Reis, Flávio

    2017-06-13

    Drug delivery systems, accompanied by nanoparticle technology, have recently emerged as prominent solutions to improve the pharmacokinetic properties, namely bioavailability, of therapeutic and nutraceutical agents. Solid lipid nanoparticles (SLNs) have received much attention from researchers due to their potential to protect or improve drug properties. SLNs have been reported to be an alternative system to traditional carriers, such as emulsions, liposomes, and polymeric nanoparticles. Phenolic compounds are widespread in plant-derived foodstuffs and therefore abundant in our diet. Over the last decades, phenolic compounds have received considerable attention due to several health promoting properties, mostly related to their antioxidant activity, which can have important implications for health. However, most of these compounds have been associated with poor bioavailability being poorly absorbed, rapidly metabolized and eliminated, which compromises its biological and pharmacological benefits. This paper provides a systematic review of the use of SLNs as oral delivery systems of phenolic compounds, in order to overcome pharmacokinetic limitations of these compounds and improved nutraceutical potential. In vitro studies, as well as works describing topical and oral treatments will be revisited and discussed. The classification, synthesis, and clinical application of these nanomaterials will be also considered in this review article.

  17. Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting

    Directory of Open Access Journals (Sweden)

    Brian C. Palmer

    2016-12-01

    Full Text Available Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

  18. Nanoparticle-Mediated Pulmonary Drug Delivery: A Review

    Directory of Open Access Journals (Sweden)

    Mukta Paranjpe

    2014-04-01

    Full Text Available Colloidal drug delivery systems have been extensively investigated as drug carriers for the application of different drugs via different routes of administration. Systems, such as solid lipid nanoparticles, polymeric nanoparticles and liposomes, have been investigated for a long time for the treatment of various lung diseases. The pulmonary route, owing to a noninvasive method of drug administration, for both local and systemic delivery of an active pharmaceutical ingredient (API forms an ideal environment for APIs acting on pulmonary diseases and disorders. Additionally, this route offers many advantages, such as a high surface area with rapid absorption due to high vascularization and circumvention of the first pass effect. Aerosolization or inhalation of colloidal systems is currently being extensively studied and has huge potential for targeted drug delivery in the treatment of various diseases. Furthermore, the surfactant-associated proteins present at the interface enhance the effect of these formulations by decreasing the surface tension and allowing the maximum effect. The most challenging part of developing a colloidal system for nebulization is to maintain the critical physicochemical parameters for successful inhalation. The following review focuses on the current status of different colloidal systems available for the treatment of various lung disorders along with their characterization. Additionally, different in vitro, ex vivo and in vivo cell models developed for the testing of these systems with studies involving cell culture analysis are also discussed.

  19. Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery

    Science.gov (United States)

    Tan, Qi; Liu, Weidong; Guo, Chenyu; Zhai, Guangxi

    2011-01-01

    Background The purpose of this study was to investigate lecithin-chitosan nanoparticles as a topical delivery system for quercetin. Methods Tocopheryl propylene glycol succinate was chosen to be the surfactant for the nanosystem. The mean particle size of the nanoparticles was 95.3 nm, and the entrapment efficiency and drug loading for quercetin were 48.5% and 2.45%, respectively. Topical delivery in vitro and in vivo of the quercetin-loaded nanoparticles was evaluated using quercetin propylene glycol solution as the control. Results Compared with quercetin solution, the quercetin-loaded nanoparticles showed higher permeation ability, and significantly increased accumulation of quercetin in the skin, especially in the epidermis. Microstructure observation of the skin surface after administration indicated that the interaction between ingredients of the nanoparticles and the skin surface markedly changed the morphology of the stratum corneum and disrupted the corneocyte layers, thus facilitating the permeation and accumulation of quercetin in skin. Conclusion Lecithin-chitosan nanoparticles are a promising carrier for topical delivery of quercetin. PMID:21904452

  20. A novel thermal and pH responsive drug delivery system based on ZnO@PNIPAM hybrid nanoparticles

    International Nuclear Information System (INIS)

    Tan, Licheng; Liu, Jian; Zhou, Weihua; Wei, Junchao; Peng, Zhiping

    2014-01-01

    A smart ZnO@PNIPAM hybrid was prepared by grafting thermal responsive poly(N-isopropylacrylamide) (PNIPAM) on zinc oxide (ZnO) nanoparticles via surface-initiated atom transfer radical polymerization (ATRP). The thermal gravimetric analysis (TGA) shows that the grafting amount of PNIPAM was about 38%, and the SEM images show that the PNIPAM chains can prevent the aggregation of ZnO nanoparticles. The responsive properties of ZnO@PNIPAM were measured by photoluminescence spectra, and the results demonstrate that the PNIPAM chains grafted on ZnO surfaces can realize reversible thermal responsive and photoluminescence properties. An anticancer drug, doxorubicin (Dox), was used as a model drug and loaded into the hybrid nanoparticles, and an in vitro drug release test implied that ZnO@PNIPAM could work as a thermal responsive drug delivery system. Furthermore, pH sensitive drug releases were carried out in acetate buffer at pH 5.0 and pH 6.0 and in water at pH 7.0, and the results showed evident pH dependency, showing its pH responsive properties. - Graphical abstract: In this manuscript, thermal responsive poly(N-isopropylacrylamide) (PNIPAM) was grafted on the surface of ZnO nanoparticles. The obtained ZnO@PNIPAM hybrid showed reversible thermal responsive photoluminescent properties, and can also work as a thermal and pH responsive drug delivery system. - Highlights: • The ZnO@PNIPAM hybrid was prepared via ATRP. • The ZnO@PNIPAM hybrid showed thermal responsive properties. • The ZnO@PNIPAM hybrid can work as a thermal and pH responsive drug delivery system

  1. Preparation and characterization of 6-mercaptopurine-coated magnetite nanoparticles as a drug delivery system.

    Science.gov (United States)

    Dorniani, Dena; Hussein, Mohd Zobir Bin; Kura, Aminu Umar; Fakurazi, Sharida; Shaari, Abdul Halim; Ahmad, Zalinah

    2013-01-01

    Iron oxide nanoparticles are of considerable interest because of their use in magnetic recording tape, ferrofluid, magnetic resonance imaging, drug delivery, and treatment of cancer. The specific morphology of nanoparticles confers an ability to load, carry, and release different types of drugs. We synthesized superparamagnetic nanoparticles containing pure iron oxide with a cubic inverse spinal structure. Fourier transform infrared spectra confirmed that these Fe3O4 nanoparticles could be successfully coated with active drug, and thermogravimetric and differential thermogravimetric analyses showed that the thermal stability of iron oxide nanoparticles coated with chitosan and 6-mercaptopurine (FCMP) was markedly enhanced. The synthesized Fe3O4 nanoparticles and the FCMP nanocomposite were generally spherical, with an average diameter of 9 nm and 19 nm, respectively. The release of 6-mercaptopurine from the FCMP nanocomposite was found to be sustained and governed by pseudo-second order kinetics. In order to improve drug loading and release behavior, we prepared a novel nanocomposite (FCMP-D), ie, Fe3O4 nanoparticles containing the same amounts of chitosan and 6-mercaptopurine but using a different solvent for the drug. The results for FCMP-D did not demonstrate "burst release" and the maximum percentage release of 6-mercaptopurine from the FCMP-D nanocomposite reached about 97.7% and 55.4% within approximately 2,500 and 6,300 minutes when exposed to pH 4.8 and pH 7.4 solutions, respectively. By MTT assay, the FCMP nanocomposite was shown not to be toxic to a normal mouse fibroblast cell line. Iron oxide coated with chitosan containing 6-mercaptopurine prepared using a coprecipitation method has the potential to be used as a controlled-release formulation. These nanoparticles may serve as an alternative drug delivery system for the treatment of cancer, with the added advantage of sparing healthy surrounding cells and tissue.

  2. Ligand-Modified Human Serum Albumin Nanoparticles for Enhanced Gene Delivery.

    Science.gov (United States)

    Look, Jennifer; Wilhelm, Nadine; von Briesen, Hagen; Noske, Nadja; Günther, Christine; Langer, Klaus; Gorjup, Erwin

    2015-09-08

    The development of nonviral gene delivery systems is a great challenge to enable safe gene therapy. In this study, ligand-modified nanoparticles based on human serum albumin (HSA) were developed and optimized for an efficient gene therapy. Different glutaraldehyde cross-linking degrees were investigated to optimize the HSA nanoparticles for gene delivery. The peptide sequence arginine-glycine-aspartate (RGD) and the HIV-1 transactivator of transduction sequence (Tat) are well-known as promising targeting ligands. Plasmid DNA loaded HSA nanoparticles were covalently modified on their surface with these different ligands. The transfection potential of the obtained plasmid DNA loaded RGD- and Tat-modified nanoparticles was investigated in vitro, and optimal incubation conditions for these preparations were studied. It turned out that Tat-modified HSA nanoparticles with the lowest cross-linking degree of 20% showed the highest transfection potential. Taken together, ligand-functionalized HSA nanoparticles represent promising tools for efficient and safe gene therapy.

  3. Tumor vascular-targeted co-delivery of anti-angiogenesis and chemotherapeutic agents by mesoporous silica nanoparticle-based drug delivery system for synergetic therapy of tumor

    Directory of Open Access Journals (Sweden)

    Li X

    2015-12-01

    Full Text Available Xiaoyu Li, Meiying Wu, Limin Pan, Jianlin Shi State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: To overcome the drawback of drug non-selectivity in traditional chemotherapy, the construction of multifunctional targeting drug delivery systems is one of the most effective and prevailing approaches. The intratumoral anti-angiogenesis and the tumor cell-killing are two basic approaches in fighting tumors. Herein we report a novel tumor vascular-targeting multidrug delivery system using mesoporous silica nanoparticles as carrier to co-load an antiangiogenic agent (combretastatin A4 and a chemotherapeutic drug (doxorubicin and conjugate with targeting molecules (iRGD peptide for combined anti-angiogenesis and chemotherapy. Such a dual-loaded drug delivery system is capable of delivering the two agents at tumor vasculature and then within tumors through a differentiated drug release strategy, which consequently results in greatly improved antitumor efficacy at a very low doxorubicin dose of 1.5 mg/kg. The fast release of the antiangiogenic agent at tumor vasculatures led to the disruption of vascular structure and had a synergetic effect with the chemotherapeutic drug slowly released in the following delivery of chemotherapeutic drug into tumors. Keywords: mesoporous silica nanoparticles, drug delivery, tumor vasculatures targeting, antiangiogenic agent

  4. Receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient delivery system for MRTF silencing in conjunctival fibrosis.

    Science.gov (United States)

    Yu-Wai-Man, Cynthia; Tagalakis, Aristides D; Manunta, Maria D; Hart, Stephen L; Khaw, Peng T

    2016-02-24

    There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye.

  5. Preparation and characterization of 6-mercaptopurine-coated magnetite nanoparticles as a drug delivery system

    Directory of Open Access Journals (Sweden)

    Dorniani D

    2013-09-01

    . By MTT assay, the FCMP nanocomposite was shown not to be toxic to a normal mouse fibroblast cell line. Conclusion: Iron oxide coated with chitosan containing 6-mercaptopurine prepared using a coprecipitation method has the potential to be used as a controlled-release formulation. These nanoparticles may serve as an alternative drug delivery system for the treatment of cancer, with the added advantage of sparing healthy surrounding cells and tissue. Keywords: superparamagnetic nanoparticles, 6-mercaptopurine, controlled release, cytotoxicity, drug delivery

  6. Enabling Anticancer Therapeutics by Nanoparticle Carriers: The Delivery of Paclitaxel

    Directory of Open Access Journals (Sweden)

    Bing Yan

    2011-07-01

    Full Text Available Anticancer drugs, such as paclitaxel (PTX, are indispensable for the treatment of a variety of malignancies. However, the application of most drugs is greatly limited by the low water solubility, poor permeability, or high efflux from cells. Nanoparticles have been widely investigated to enable drug delivery due to their low toxicity, sustained drug release, molecular targeting, and additional therapeutic and imaging functions. This review takes paclitaxel as an example and compares different nanoparticle-based delivery systems for their effectiveness in cancer chemotherapy.

  7. Silver nanoparticles delivery system based on natural rubber latex membranes

    Energy Technology Data Exchange (ETDEWEB)

    Guidelli, Eder Jose, E-mail: ederguidelli@gmail.com [Universidade de Sao Paulo/FFCLRP-DF (Brazil); Kinoshita, Angela [Universidade do Sagrado Coracao (Brazil); Ramos, Ana Paula [Universidade de Sao Paulo/FFCLRP-DQ (Brazil); Baffa, Oswaldo [Universidade de Sao Paulo/FFCLRP-DF (Brazil)

    2013-04-15

    The search for new materials for biomedical applications is extremely important. Here, we present results on the performance of a silver nanoparticles delivery system using natural rubber latex (NRL) as the polymeric matrix. Our aim was to obtain an optimized wound dressing by combining materials with potential healing action. The synthesis of silver nanoparticles and their characterization by UV-Vis spectroscopy, transmission electron microscopy, zeta potential, dynamic light scattering, and Fourier transform infrared spectroscopy (FTIR) are depicted. The NRL membranes are good matrix for silver nanoparticles and allow for their gradual release. The release of 30 nm silver nanoparticles by the NRL membranes depends on their mass percentage in NRL membranes. The total concentration of AgNP released by the NRL membranes was calculated. The AgNP attached to the cis-isoprene molecules in the NRL matrix remain attached to the membrane ({approx}0.1 % w/w). So, only the AgNP bound to the non-rubber molecules are released. FTIR spectra suggest that non-rubber molecules, like aminoacids and proteins, associated with the serum fraction of the NRL may be attached to the surfaces of the released nanoparticles, thereby increasing the release of such molecules. The released silver nanoparticles are sterically stabilized, more stable and well dispersed. Because the serum fraction of the NRL is responsible for the angiogenic properties of the matrix, the silver nanoparticles could increment the angiogenic properties of NRL. This biomaterial has desirable properties for the fabrication of a wound dressing with potential healing action, since it combines the angiogenic and antibacterial properties of the silver nanoparticles with the increased angiogenic properties of the NRL.Graphical AbstractThe AgNP attached to the cis-isoprene molecules remain in the NRL matrix and only the AgNP bound to the non-rubber molecules (NRL serum fraction) are released. The released AgNP are

  8. Silver nanoparticles delivery system based on natural rubber latex membranes

    International Nuclear Information System (INIS)

    Guidelli, Éder José; Kinoshita, Angela; Ramos, Ana Paula; Baffa, Oswaldo

    2013-01-01

    The search for new materials for biomedical applications is extremely important. Here, we present results on the performance of a silver nanoparticles delivery system using natural rubber latex (NRL) as the polymeric matrix. Our aim was to obtain an optimized wound dressing by combining materials with potential healing action. The synthesis of silver nanoparticles and their characterization by UV–Vis spectroscopy, transmission electron microscopy, zeta potential, dynamic light scattering, and Fourier transform infrared spectroscopy (FTIR) are depicted. The NRL membranes are good matrix for silver nanoparticles and allow for their gradual release. The release of 30 nm silver nanoparticles by the NRL membranes depends on their mass percentage in NRL membranes. The total concentration of AgNP released by the NRL membranes was calculated. The AgNP attached to the cis-isoprene molecules in the NRL matrix remain attached to the membrane (∼0.1 % w/w). So, only the AgNP bound to the non-rubber molecules are released. FTIR spectra suggest that non-rubber molecules, like aminoacids and proteins, associated with the serum fraction of the NRL may be attached to the surfaces of the released nanoparticles, thereby increasing the release of such molecules. The released silver nanoparticles are sterically stabilized, more stable and well dispersed. Because the serum fraction of the NRL is responsible for the angiogenic properties of the matrix, the silver nanoparticles could increment the angiogenic properties of NRL. This biomaterial has desirable properties for the fabrication of a wound dressing with potential healing action, since it combines the angiogenic and antibacterial properties of the silver nanoparticles with the increased angiogenic properties of the NRL.Graphical AbstractThe AgNP attached to the cis-isoprene molecules remain in the NRL matrix and only the AgNP bound to the non-rubber molecules (NRL serum fraction) are released. The released AgNP are sterically

  9. Long circulating polymeric nanoparticles for gene/drug delivery.

    Science.gov (United States)

    Hu, Jiaming; Sheng, Yan; Shi, Junfeng; Yu, Bohao; Yu, Zhiqiang; Liao, Guochao

    2017-12-07

    The major limitation in the improving polymeric nanoparticles into an efficient gene/drug delivery carrier is the rapid opsonization, phagocytic uptake by mononuclear phagocyte system and subsequent clearance from the bloodstream. The prolonged circulation time of nanoparticles in the blood is a prerequisite to realizing a controlled and targeted (passive or active targeting) release of the encapsulated gene/drug at the desired site of action. In this review, the factors such as biological barriers and physical barriers including particle size, shape, zeta potential, and hydrophilicity will be discussed, which can cause effects on blood clearance and organ accumulation. Some natural and synthetic polymers utilized in long-circulating nanoparticles will also be discussed. The most popular method to mask or camouflage nanoparticles is the adsorbed, grafted or conjugated of poly (ethylene glycol) (PEG) or other hydrophilic polymers (e.g. polysaccharides) to the particle surface. Surface modification of nanoparticles with these polymers results in an increased blood circulation time by several orders of magnitude in comparison to the bare nanoparticles. However, the circulation half-life of nanoparticles still cannot satisfy the need for clinical use. At present, identification of novel potential coating materials is an emerging field of interest in the design of long-circulating polymer-based nanoparticulate gene/drug delivery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Colloidal drug delivery system: amplify the ocular delivery.

    Science.gov (United States)

    Ali, Javed; Fazil, Mohd; Qumbar, Mohd; Khan, Nazia; Ali, Asgar

    2016-01-01

    The ocular perceivers are the most voluntarily accessible organs in terms of location in the body, yet drug distribution to these tissues is one of the most intriguing and challenging endeavors and problematic to the pharmaceutical scientist. The most of ocular diseases are treated with topical application of conventional formulation, i.e. solutions, suspensions and ointment. Typically on installation of these conventional formulations, only <5% of the applied dose penetrates the cornea and reaches intraocular tissues, while a major fraction of the instilled dose is wastage due to the presence of many ocular barriers like external barriers, rapid loss of the instilled solution from the precorneal area and nasolacrimal drainage system. Systemic absorption caused systemic side effects varying from mild to life-threatening events. The main objective of this review is to explore the role of colloidal delivery of drug to minimize the drawbacks associated with them. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings and applications of colloidal delivery systems, i.e. nanoparticles, nanosuspensions, liposomes, niosomes, dendrimers and contact lenses containing nanoparticles have the capacity to distribute ocular drugs to categorical target sites and hold promise to revolutionize the therapy of many ocular perceiver diseases and minimized the circumscription of conventional delivery. Form the basis of literature review, it has been found that the novel delivery system have greater impact to maximize ocular drug absorption, and minimize systemic absorption and side effects.

  11. Novel thermo-sensitive core-shell nanoparticles for targeted paclitaxel delivery

    International Nuclear Information System (INIS)

    Li Yuanpei; Pan Shirong; Zhang Wei; Du Zhuo

    2009-01-01

    Novel thermo-sensitive nanoparticles self-assembled from poly(N,N-diethylacrylamide- co-acrylamide)-block-poly(γ-benzyl L-glutamate) were designed for targeted drug delivery in localized hyperthermia. The lower critical solution temperature (LCST) of nanoparticles was adjusted to a level between physiological body temperature (37 deg. C) and that used in local hyperthermia (about 43 deg. C). The temperature-dependent performances of the core-shell nanoparticles were systemically studied by nuclear magnetic resonance (NMR), circular dichroism (CD), fluorescence spectroscopy, dynamic light scattering (DLS), and atom force microscopy (AFM). The mean diameter of the nanoparticles increased slightly from 110 to 129 nm when paclitaxel (PTX), a poorly water-soluble anti-tumor drug, was encapsulated. A stability study in bovine serum albumin (BSA) solution indicated that the PTX loaded nanoparticles may have a long circulation time under physiological environments as the LCST was above physiological body temperature and the shell remained hydrophilic at 37 deg.C. The PTX release profiles showed thermo-sensitive controlled behavior. The proliferation inhibiting activity of PTX loaded nanoparticles was evaluated against Hela cells in vitro, compared with Taxol (a formulation of paclitaxel dissolved in Cremophor EL and ethanol). The cytotoxicity of PTX loaded nanoparticles increased obviously when hyperthermia was performed. The nanoparticles synthesized here could be an ideal candidate for thermal triggered anti-tumor PTX delivery system.

  12. Synthesis and characterization of novel amphiphilic copolymer stearic acid-coupled F127 nanoparticles for nano-technology based drug delivery system.

    Science.gov (United States)

    Gao, Qihe; Liang, Qing; Yu, Fei; Xu, Jian; Zhao, Qihua; Sun, Baiwang

    2011-12-01

    Pluronic, F127, amphiphilic block copolymers, are used for several applications, including drug delivery systems. The critical micelle concentration (CMC) of F127 is about 0.26-0.8 wt% so that the utility of F127 in nano-technology based drug delivery system is limited since the nano-sized micelles could dissociate upon dilution. Herein, stearic acid (SA) was simply coupled to F127 between the carboxyl group of SA and the hydroxyl group of F127, which formed a novel copolymer named as SA-coupled F127, with significantly lower CMC. Above the CMC 6.9 × 10(-5)wt%, SA-coupled F127 self-assembled stable nanoparticles with Zeta potential -36 mV. Doxorubicin (DOX)-loaded nanoparticles were made, with drug loading (DL) 5.7 wt% and Zeta potential -36 to -39 mV, and the nanoparticles exhibited distinct shape with the size distribution from 20 to 50 nm. DOX-loaded nanoparticles were relatively stable and exhibited DOX dependant cytotoxicity toward MCF-7 cells in vitro. These results suggest that SA-coupled F127 potentially could be applied as a nano-technology based drug delivery method. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. T cells enhance gold nanoparticle delivery to tumors in vivo

    Science.gov (United States)

    Kennedy, Laura C.; Bear, Adham S.; Young, Joseph K.; Lewinski, Nastassja A.; Kim, Jean; Foster, Aaron E.; Drezek, Rebekah A.

    2011-12-01

    Gold nanoparticle-mediated photothermal therapy (PTT) has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs) are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR) effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production). Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.

  14. Fabrication and characterization of an inorganic gold and silica nanoparticle mediated drug delivery system for nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Das, Amitava; Singla, Sumit K; Shah, Vijay H [Gastroenterology Research Unit, Department of Internal Medicine, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905 (United States); Mukherjee, Priyabrata; Mukhopadhyay, Debabrata; Patra, Chitta Ranjan [Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905 (United States); Guturu, Praveen [Department of Internal Medicine, UTMB, Galveston, TX 77555 (United States); Frost, Megan C, E-mail: patra.chittaranjan@mayo.edu, E-mail: patra.chitta@gmail.com [Department of Biomedical Engineering, Michigan Technological University, Houghton, MI 49931 (United States)

    2010-07-30

    Nitric oxide (NO) plays an important role in inhibiting the development of hepatic fibrosis and its ensuing complication of portal hypertension by inhibiting human hepatic stellate cell (HSC) activation. Here we have developed a gold nanoparticle and silica nanoparticle mediated drug delivery system containing NO donors, which could be used for potential therapeutic application in chronic liver disease. The gold nanoconjugates were characterized using several physico-chemical techniques such as UV-visible spectroscopy and transmission electron microscopy. Silica nanoconjugates were synthesized and characterized as reported previously. NO released from gold and silica nanoconjugates was quantified under physiological conditions (pH = 7.4 at 37 deg. C) for a substantial period of time. HSC proliferation and the vascular tube formation ability, manifestations of their activation, were significantly attenuated by the NO released from these nanoconjugates. This study indicates that gold and silica nanoparticle mediated drug delivery systems for introducing NO could be used as a strategy for the treatment of hepatic fibrosis or chronic liver diseases, by limiting HSC activation.

  15. Fabrication and characterization of an inorganic gold and silica nanoparticle mediated drug delivery system for nitric oxide

    International Nuclear Information System (INIS)

    Das, Amitava; Singla, Sumit K; Shah, Vijay H; Mukherjee, Priyabrata; Mukhopadhyay, Debabrata; Patra, Chitta Ranjan; Guturu, Praveen; Frost, Megan C

    2010-01-01

    Nitric oxide (NO) plays an important role in inhibiting the development of hepatic fibrosis and its ensuing complication of portal hypertension by inhibiting human hepatic stellate cell (HSC) activation. Here we have developed a gold nanoparticle and silica nanoparticle mediated drug delivery system containing NO donors, which could be used for potential therapeutic application in chronic liver disease. The gold nanoconjugates were characterized using several physico-chemical techniques such as UV-visible spectroscopy and transmission electron microscopy. Silica nanoconjugates were synthesized and characterized as reported previously. NO released from gold and silica nanoconjugates was quantified under physiological conditions (pH = 7.4 at 37 deg. C) for a substantial period of time. HSC proliferation and the vascular tube formation ability, manifestations of their activation, were significantly attenuated by the NO released from these nanoconjugates. This study indicates that gold and silica nanoparticle mediated drug delivery systems for introducing NO could be used as a strategy for the treatment of hepatic fibrosis or chronic liver diseases, by limiting HSC activation.

  16. Nanoparticle for delivery of antisense γPNA oligomers targeting CCR5.

    Science.gov (United States)

    Bahal, Raman; McNeer, Nicole Ali; Ly, Danith H; Saltzman, W Mark; Glazer, Peter M

    2013-01-01

    The development of a new class of peptide nucleic acids (PNAs), i.e., gamma PNAs (γPNAs), creates the need for a general and effective method for its delivery into cells for regulating gene expression in mammalian cells. Here we report the antisense activity of a recently developed hydrophilic and biocompatible diethylene glycol (miniPEG)-based gamma peptide nucleic acid called MPγPNAs via its delivery by poly(lactide-co-glycolide) (PLGA)-based nanoparticle system. We show that MPγPNA oligomers designed to bind to the selective region of chemokine receptor 5 (CC R5) transcript, induce potent and sequence-specific antisense effects as compared with regular PNA oligomers. In addition, PLGA nanoparticle delivery of MPγPNAs is not toxic to the cells. The findings reported in this study provide a combination of γPNA technology and PLGA-based nanoparticle delivery method for regulating gene expression in live cells via the antisense mechanism.

  17. Nanocomposite Hydrogels: 3D Polymer-Nanoparticle Synergies for On-Demand Drug Delivery.

    Science.gov (United States)

    Merino, Sonia; Martín, Cristina; Kostarelos, Kostas; Prato, Maurizio; Vázquez, Ester

    2015-05-26

    Considerable progress in the synthesis and technology of hydrogels makes these materials attractive structures for designing controlled-release drug delivery systems. In particular, this review highlights the latest advances in nanocomposite hydrogels as drug delivery vehicles. The inclusion/incorporation of nanoparticles in three-dimensional polymeric structures is an innovative means for obtaining multicomponent systems with diverse functionality within a hybrid hydrogel network. Nanoparticle-hydrogel combinations add synergistic benefits to the new 3D structures. Nanogels as carriers for cancer therapy and injectable gels with improved self-healing properties have also been described as new nanocomposite systems.

  18. Novel Polysaccharide Based Polymers and Nanoparticles for Controlled Drug Delivery and Biomedical Imaging

    Science.gov (United States)

    Shalviri, Alireza

    The use of polysaccharides as building blocks in the development of drugs and contrast agents delivery systems is rapidly growing. This can be attributed to the outstanding virtues of polysaccharides such as biocompatibility, biodegradability, upgradability, multiple reacting groups and low cost. The focus of this thesis was to develop and characterize novel starch based hydrogels and nanoparticles for delivery of drugs and imaging agents. To this end, two different systems were developed. The first system includes polymer and nanoparticles prepared by graft polymerization of polymethacrylic acid and polysorbate 80 onto starch. This starch based platform nanotechnology was developed using the design principles based on the pathophysiology of breast cancer, with applications in both medical imaging and breast cancer chemotherapy. The nanoparticles exhibited a high degree of doxorubicin loading as well as sustained pH dependent release of the drug. The drug loaded nanoparticles were significantly more effective against multidrug resistant human breast cancer cells compared to free doxorubicin. Systemic administration of the starch based nanoparticles co-loaded with doxorubicin and a near infrared fluorescent probe allowed for non-invasive real time monitoring of the nanoparticles biodistribution, tumor accumulation, and clearance. Systemic administration of the clinically relevant doses of the drug loaded particles to a mouse model of breast cancer significantly enhanced therapeutic efficacy while minimizing side effects compared to free doxorubicin. A novel, starch based magnetic resonance imaging (MRI) contrast agent with good in vitro and in vivo tolerability was formulated which exhibited superior signal enhancement in tumor and vasculature. The second system is a co-polymeric hydrogel of starch and xanthan gum with adjustable swelling and permeation properties. The hydrogels exhibited excellent film forming capability, and appeared to be particularly useful in

  19. Chitosan Based Self-Assembled Nanoparticles in Drug Delivery

    Directory of Open Access Journals (Sweden)

    Javier Pérez Quiñones

    2018-02-01

    Full Text Available Chitosan is a cationic polysaccharide that is usually obtained by alkaline deacetylation of chitin poly(N-acetylglucosamine. It is biocompatible, biodegradable, mucoadhesive, and non-toxic. These excellent biological properties make chitosan a good candidate for a platform in developing drug delivery systems having improved biodistribution, increased specificity and sensitivity, and reduced pharmacological toxicity. In particular, chitosan nanoparticles are found to be appropriate for non-invasive routes of drug administration: oral, nasal, pulmonary and ocular routes. These applications are facilitated by the absorption-enhancing effect of chitosan. Many procedures for obtaining chitosan nanoparticles have been proposed. Particularly, the introduction of hydrophobic moieties into chitosan molecules by grafting to generate a hydrophobic-hydrophilic balance promoting self-assembly is a current and appealing approach. The grafting agent can be a hydrophobic moiety forming micelles that can entrap lipophilic drugs or it can be the drug itself. Another suitable way to generate self-assembled chitosan nanoparticles is through the formation of polyelectrolyte complexes with polyanions. This paper reviews the main approaches for preparing chitosan nanoparticles by self-assembly through both procedures, and illustrates the state of the art of their application in drug delivery.

  20. pH-responsive mesoporous silica nanoparticles employed in controlled drug delivery systems for cancer treatment

    International Nuclear Information System (INIS)

    Yang, Ke-Ni; Zhang, Chun-Qiu; Wang, Wei; Wang, Paul C.; Zhou, Jian-Ping; Liang, Xing-Jie

    2014-01-01

    In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles (MSNs) with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanoparticles, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail

  1. A rapid pathway toward a superb gene delivery system: programming structural and functional diversity into a supramolecular nanoparticle library.

    Science.gov (United States)

    Wang, Hao; Liu, Kan; Chen, Kuan-Ju; Lu, Yujie; Wang, Shutao; Lin, Wei-Yu; Guo, Feng; Kamei, Ken-ichiro; Chen, Yi-Chun; Ohashi, Minori; Wang, Mingwei; Garcia, Mitch André; Zhao, Xing-Zhong; Shen, Clifton K-F; Tseng, Hsian-Rong

    2010-10-26

    Nanoparticles are regarded as promising transfection reagents for effective and safe delivery of nucleic acids into a specific type of cells or tissues providing an alternative manipulation/therapy strategy to viral gene delivery. However, the current process of searching novel delivery materials is limited due to conventional low-throughput and time-consuming multistep synthetic approaches. Additionally, conventional approaches are frequently accompanied with unpredictability and continual optimization refinements, impeding flexible generation of material diversity creating a major obstacle to achieving high transfection performance. Here we have demonstrated a rapid developmental pathway toward highly efficient gene delivery systems by leveraging the powers of a supramolecular synthetic approach and a custom-designed digital microreactor. Using the digital microreactor, broad structural/functional diversity can be programmed into a library of DNA-encapsulated supramolecular nanoparticles (DNA⊂SNPs) by systematically altering the mixing ratios of molecular building blocks and a DNA plasmid. In vitro transfection studies with DNA⊂SNPs library identified the DNA⊂SNPs with the highest gene transfection efficiency, which can be attributed to cooperative effects of structures and surface chemistry of DNA⊂SNPs. We envision such a rapid developmental pathway can be adopted for generating nanoparticle-based vectors for delivery of a variety of loads.

  2. Design and development of hyaluronan-functionalized polybenzofulvene nanoparticles as CD44 receptor mediated drug delivery system

    Science.gov (United States)

    Licciardi, Mariano; Scialabba, Cinzia; Giammona, Gaetano; Paolino, Marco; Razzano, Vincenzo; Grisci, Giorgio; Giuliani, Germano; Makovec, Francesco; Cappelli, Andrea

    2017-06-01

    A tri-component polymer brush (TCPB ), composed of a polybenzofulvene copolymer bearing low molecular weight hyaluronic acid (HA) on the surface of its cylindrical brush-like backbone and oligo-PEG fractions, was employed in the preparation of 350 nm nanostructured drug delivery systems capable of delivering the anticancer drug doxorubicin. The obtained drug delivery systems were characterized on the basis of drug loading and release, dimensions and zeta potential, morphology and in vitro cell activity, and uptake on three different human cell lines, namely the bronchial epithelial 16HBE, the breast adenocarcinoma MCF-7, and the colon cancer HCT116 cells. Finally, the ability of doxorubicin-loaded TCPB nanoparticles (DOXO-TCPB) to be internalized into cancer cells by CD44 receptor mediated uptake was assessed by means of uptake studies in HCT cells. These data were supported by anti-CD44-FITC staining assay. The proposed TCPB nanostructured drug delivery systems have many potential applications in nanomedicine, including cancer targeted drug delivery.

  3. Construction and evaluation of controlled-release delivery system of Abamectin using porous silica nanoparticles as carriers.

    Science.gov (United States)

    Wang, Yan; Cui, Haixin; Sun, Changjiao; Zhao, Xiang; Cui, Bo

    2014-12-01

    Photolysis and poor solubility in water of Abamectin are key issues to be addressed, which causes low bioavailability and residual pollution. In this study, a novel hydrophilic delivery system through loading Abamectin with porous silica nanoparticles (Abam-PSNs) was developed in order to improve the chemical stability, dispersity, and the controlled release of Abamectin. These results suggest that Abam-PSNs can significantly improve the performance of controllable release, photostability, and water solubility of Abamectin by changing the porous structure of silica nanoparticles, which is favorable to improve the bioavailability and reduce the residues of pesticides.

  4. Nanoparticle-stabilized liposomes for pH-responsive gastric drug delivery.

    Science.gov (United States)

    Thamphiwatana, Soracha; Fu, Victoria; Zhu, Jingying; Lu, Diannan; Gao, Weiwei; Zhang, Liangfang

    2013-10-01

    We report a novel pH-responsive gold nanoparticle-stabilized liposome system for gastric antimicrobial delivery. By adsorbing small chitosan-modified gold nanoparticles (diameter ~10 nm) onto the outer surface of negatively charged phospholipid liposomes (diameter ~75 nm), we show that at gastric pH the liposomes have excellent stability with limited fusion ability and negligible cargo releases. However, when the stabilized liposomes are present in an environment with neutral pH, the gold stabilizers detach from the liposomes, resulting in free liposomes that can actively fuse with bacterial membranes. Using Helicobacter pylori as a model bacterium and doxycycline as a model antibiotic, we demonstrate such pH-responsive fusion activity and drug release profile of the nanoparticle-stabilized liposomes. Particularly, at neutral pH the gold nanoparticles detach, and thus the doxycycline-loaded liposomes rapidly fuse with bacteria and cause superior bactericidal efficacy as compared to the free doxycycline counterpart. Our results suggest that the reported liposome system holds a substantial potential for gastric drug delivery; it remains inactive (stable) in the stomach lumen but actively interacts with bacteria once it reaches the mucus layer of the stomach where the bacteria may reside.

  5. Silica nanoparticles as vehicles for therapy delivery in neurological injury

    Science.gov (United States)

    Schenk, Desiree

    Acrolein, a very reactive aldehyde, is a culprit in the biochemical cascade after primary, mechanical spinal cord injury (SCI), which leads to the destruction of tissue initially unharmed, referred to as "secondary injury". Additionally, in models of multiple sclerosis (MS) and some clinical research, acrolein levels are significantly increased. This aldehyde overwhelms the natural anti-oxidant system, reacts freely with proteins, and releases during lipid peroxidation (LPO), effectively regenerating its self. Due to its ability to make more copies of itself in the presence of tissue via lipid peroxidation, researchers believe that acrolein plays a role in the increased destruction of the central nervous system in both SCI and MS. Hydralazine, an FDA-approved hypertension drug, has been shown to scavenge acrolein, but its side effects and short half life at the appropriate dose for acrolein scavenging must be improved for beneficial clinical translation. Due to the inefficient delivery of therapeutic drugs, nanoparticles have become a major field of exploration for medical applications. Based on their material properties, they can help treat disease by delivering drugs to specific tissues, enhancing detection methods, or a mixture of both. Nanoparticles made from silica provide distinct advantages. They form porous networks that can carry therapeutic molecules throughout the body. Therefore, a nanomedical approach has been designed using silica nanoparticles as a porous delivery vehicle hydralazine. The silica nanoparticles are formed in a one-step method that incorporates poly(ethylene) glycol (PEG), a stealth molecule, directly onto the nanoparticles. As an additional avenue for study, a natural product in green tea, epigallocatechin gallate (EGCG), has been explored for its ability to react with acrolein, disabling its reactive capabilities. Upon demonstration of attenuating acrolein, EGCG's delivery may also be improved using the nanomedical approach. The

  6. Delivery of Fluorescent Nanoparticles to the Brain.

    Science.gov (United States)

    Shimoni, Olga; Shi, Bingyang; Adlard, Paul A; Bush, Ashley I

    2016-11-01

    Nanotechnology applications in neuroscience promises to deliver significant scientific and technological breakthroughs, providing answers to unresolved questions regarding the processes occurring in the brain. In this perspective, we provide a short background on two distinct fluorescent nanoparticles and summarize several studies focussed on achieving delivery of these into the brain and their interaction with brain tissue. Furthermore, we discuss challenges and opportunities for further development of nanoparticle-based therapies for targeting delivery of drugs across the blood-brain barrier.

  7. Mesoporous silica nanoparticles for stimuli-responsive controlled drug delivery: advances, challenges, and outlook

    Directory of Open Access Journals (Sweden)

    Song Y

    2016-12-01

    Full Text Available Yuanhui Song, Yihong Li, Qien Xu, Zhe Liu Wenzhou Institute of Biomaterials and Engineering (WIBE, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Abstract: With the development of nanotechnology, the application of nanomaterials in the field of drug delivery has attracted much attention in the past decades. Mesoporous silica nanoparticles as promising drug nanocarriers have become a new area of interest in recent years due to their unique properties and capabilities to efficiently entrap cargo molecules. This review describes the latest advances on the application of mesoporous silica nanoparticles in drug delivery. In particular, we focus on the stimuli-responsive controlled release systems that are able to respond to intracellular environmental changes, such as pH, ATP, GSH, enzyme, glucose, and H2O2. Moreover, drug delivery induced by exogenous stimuli including temperature, light, magnetic field, ultrasound, and electricity is also summarized. These advanced technologies demonstrate current challenges, and provide a bright future for precision diagnosis and treatment. Keywords: mesoporous silica nanoparticle, drug delivery system, controlled release, stimuli-responsive, chemotherapy

  8. Diatomite silica nanoparticles for drug delivery

    OpenAIRE

    Ruggiero, Immacolata; Terracciano, Monica; Martucci, Nicola M; De Stefano, Luca; Migliaccio, Nunzia; Tatè, Rosarita; Rendina, Ivo; Arcari, Paolo; Lamberti, Annalisa; Rea, Ilaria

    2014-01-01

    Diatomite is a natural fossil material of sedimentary origin, constituted by fragments of diatom siliceous skeletons. In this preliminary work, the properties of diatomite nanoparticles as potential system for the delivery of drugs in cancer cells were exploited. A purification procedure, based on thermal treatments in strong acid solutions, was used to remove inorganic and organic impurities from diatomite and to make them a safe material for medical applications. The micrometric diatomite p...

  9. Development and characterization of multifunctional nanoparticles for drug delivery to cancer cells

    Science.gov (United States)

    Nahire, Rahul Rajaram

    Lipid and polymeric nanoparticles, although proven to be effective drug delivery systems compared to free drugs, have shown considerable limitations pertaining to their uptake and release at tumor sites. Spatial and temporal control over the delivery of anticancer drugs has always been challenge to drug delivery scientists. Here, we have developed and characterized multifunctional nanoparticles (liposomes and polymersomes) which are targeted specifically to cancer cells, and release their contents with tumor specific internal triggers. To enable these nanoparticles to be tracked in blood circulation, we have imparted them with echogenic characteristic. Echogenicity of nanoparticles is evaluated using ultrasound scattering and imaging experiments. Nanoparticles demonstrated effective release with internal triggers such as elevated levels of MMP-9 enzyme found in the extracellular matrix of tumor cells, decreased pH of lysosome, and differential concentration of reducing agents in cytosol of cancer cells. We have also successfully demonstrated the sensitivity of these particles towards ultrasound to further enhance the release with internal triggers. To ensure the selective uptake by folate receptor- overexpressing cancer cells, we decorated these nanoparticles with folic acid on their surface. Fluorescence microscopic images showed significantly higher uptake of folate-targeted nanoparticles by MCF-7 (breast cancer) and PANC-1 (pancreatic cancer) cells compared to particles without any targeting ligand on their surface. To demonstrate the effectiveness of these nanoparticles to carry the drugs inside and kill cancer cells, we encapsulated doxorubicin and/or gemcitabine employing the pH gradient method. Drug loaded nanoparticles showed significantly higher killing of the cancer cells compared to their non-targeted counterparts and free drugs. With further development, these nanoparticles certainly have potential to be used as a multifunctional nanocarriers for image

  10. Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery.

    Science.gov (United States)

    Gao, Ning; Bozeman, Erica N; Qian, Weiping; Wang, Liya; Chen, Hongyu; Lipowska, Malgorzata; Staley, Charles A; Wang, Y Andrew; Mao, Hui; Yang, Lily

    2017-01-01

    The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.

  11. PLGA Nanoparticles for Ultrasound-Mediated Gene Delivery to Solid Tumors

    Directory of Open Access Journals (Sweden)

    Marxa Figueiredo

    2012-01-01

    Full Text Available This paper focuses on novel approaches in the field of nanotechnology-based carriers utilizing ultrasound stimuli as a means to spatially target gene delivery in vivo, using nanoparticles made with either poly(lactic-co-glycolic acid (PLGA or other polymers. We specifically discuss the potential for gene delivery by particles that are echogenic (amenable to destruction by ultrasound composed either of polymers (PLGA, polystyrene or other contrast agent materials (Optison, SonoVue microbubbles. The use of ultrasound is an efficient tool to further enhance gene delivery by PLGA or other echogenic particles in vivo. Echogenic PLGA nanoparticles are an attractive strategy for ultrasound-mediated gene delivery since this polymer is currently approved by the US Food and Drug Administration for drug delivery and diagnostics in cancer, cardiovascular disease, and also other applications such as vaccines and tissue engineering. This paper will review recent successes and the potential of applying PLGA nanoparticles for gene delivery, which include (a echogenic PLGA used with ultrasound to enhance local gene delivery in tumors or muscle and (b PLGA nanoparticles currently under development, which could benefit in the future from ultrasound-enhanced tumor targeted gene delivery.

  12. A novel nanoparticle formulation for sustained paclitaxel delivery.

    Science.gov (United States)

    Trickler, W J; Nagvekar, A A; Dash, A K

    2008-01-01

    To develop a novel nanoparticle drug delivery system consisting of chitosan and glyceryl monooleate (GMO) for the delivery of a wide variety of therapeutics including paclitaxel. Chitosan/GMO nanoparticles were prepared by multiple emulsion (o/w/o) solvent evaporation methods. Particle size and surface charge were determined. The morphological characteristics and cellular adhesion were evaluated with surface or transmission electron microscopy methods. The drug loading, encapsulation efficiency, in vitro release and cellular uptake were determined using HPLC methods. The safety and efficacy were evaluated by MTT cytotoxicity assay in human breast cancer cells (MDA-MB-231). These studies provide conceptual proof that chitosan/GMO can form polycationic nano-sized particles (400 to 700 nm). The formulation demonstrates high yields (98 to 100%) and similar entrapment efficiencies. The lyophilized powder can be stored and easily be resuspended in an aqueous matrix. The nanoparticles have a hydrophobic inner-core with a hydrophilic coating that exhibits a significant positive charge and sustained release characteristics. This novel nanoparticle formulation shows evidence of mucoadhesive properties; a fourfold increased cellular uptake and a 1000-fold reduction in the IC(50) of PTX. These advantages allow lower doses of PTX to achieve a therapeutic effect, thus presumably minimizing the adverse side effects.

  13. Biosensor-controlled gene therapy/drug delivery with nanoparticles for nanomedicine

    Science.gov (United States)

    Prow, Tarl W.; Rose, William A.; Wang, Nan; Reece, Lisa M.; Lvov, Yuri; Leary, James F.

    2005-04-01

    Nanomedicine involves cell-by-cell regenerative medicine, either repairing cells one at a time or triggering apoptotic pathways in cells that are not repairable. Multilayered nanoparticle systems are being constructed for the targeted delivery of gene therapy to single cells. Cleavable shells containing targeting, biosensing, and gene therapeutic molecules are being constructed to direct nanoparticles to desired intracellular targets. Therapeutic gene sequences are controlled by biosensor-activated control switches to provide the proper amount of gene therapy on a single cell basis. The central idea is to set up gene therapy "nanofactories" inside single living cells. Molecular biosensors linked to these genes control their expression. Gene delivery is started in response to a biosensor detected problem; gene delivery is halted when the cell response indicates that more gene therapy is not needed. Cell targeting of nanoparticles, both nanocrystals and nanocapsules, has been tested by a combination of fluorescent tracking dyes, fluorescence microscopy and flow cytometry. Intracellular targeting has been tested by confocal microscopy. Successful gene delivery has been visualized by use of GFP reporter sequences. DNA tethering techniques were used to increase the level of expression of these genes. Integrated nanomedical systems are being designed, constructed, and tested in-vitro, ex-vivo, and in small animals. While still in its infancy, nanomedicine represents a paradigm shift in thinking-from destruction of injured cells by surgery, radiation, chemotherapy to cell-by-cell repair within an organ and destruction of non-repairable cells by natural apoptosis.

  14. NIR-to-visible upconversion nanoparticles for fluorescent labeling and targeted delivery of siRNA

    International Nuclear Information System (INIS)

    Jiang Shan; Zhang Yong; Lim, Kian Meng; Sim, Eugene K W; Ye Lei

    2009-01-01

    Near-infrared (NIR)-to-visible upconversion fluorescent nanoparticles were synthesized and used for imaging and targeted delivery of small interfering RNA (siRNA) to cancer cells. Silica-coated NaYF 4 upconversion nanoparticles (UCNs) co-doped with lanthanide ions (Yb/Er) were synthesized. Folic acid and anti-Her2 antibody conjugated UCNs were used to fluorescently label the folate receptors of HT-29 cells and Her2 receptors of SK-BR-3 cells, respectively. The intracellular uptake of the folic acid and antibody conjugated UCNs was visualized using a confocal fluorescence microscope equipped with an NIR laser. siRNA was attached to anti-Her2 antibody conjugated UCNs and the delivery of these nanoparticles to SK-BR-3 cells was studied. Meanwhile, a luciferase assay was established to confirm the gene silencing effect of siRNA. Upconversion nanoparticles can serve as a fluorescent probe and delivery system for simultaneous imaging and delivery of biological molecules.

  15. NIR-to-visible upconversion nanoparticles for fluorescent labeling and targeted delivery of siRNA

    Science.gov (United States)

    Jiang, Shan; Zhang, Yong; Lim, Kian Meng; Sim, Eugene K. W.; Ye, Lei

    2009-04-01

    Near-infrared (NIR)-to-visible upconversion fluorescent nanoparticles were synthesized and used for imaging and targeted delivery of small interfering RNA (siRNA) to cancer cells. Silica-coated NaYF4 upconversion nanoparticles (UCNs) co-doped with lanthanide ions (Yb/Er) were synthesized. Folic acid and anti-Her2 antibody conjugated UCNs were used to fluorescently label the folate receptors of HT-29 cells and Her2 receptors of SK-BR-3 cells, respectively. The intracellular uptake of the folic acid and antibody conjugated UCNs was visualized using a confocal fluorescence microscope equipped with an NIR laser. siRNA was attached to anti-Her2 antibody conjugated UCNs and the delivery of these nanoparticles to SK-BR-3 cells was studied. Meanwhile, a luciferase assay was established to confirm the gene silencing effect of siRNA. Upconversion nanoparticles can serve as a fluorescent probe and delivery system for simultaneous imaging and delivery of biological molecules.

  16. Hydrogel nanoparticles and nanocomposites for nasal drug/vaccine delivery.

    Science.gov (United States)

    Salatin, Sara; Barar, Jaleh; Barzegar-Jalali, Mohammad; Adibkia, Khosro; Milani, Mitra Alami; Jelvehgari, Mitra

    2016-09-01

    Over the past few years, nasal drug delivery has attracted more and more attentions, and been recognized as the most promising alternative route for the systemic medication of drugs limited to intravenous administration. Many experiments in animal models have shown that nanoscale carriers have the ability to enhance the nasal delivery of peptide/protein drugs and vaccines compared to the conventional drug solution formulations. However, the rapid mucociliary clearance of the drug-loaded nanoparticles can cause a reduction in bioavailability percentage after intranasal administration. Thus, research efforts have considerably been directed towards the development of hydrogel nanosystems which have mucoadhesive properties in order to maximize the residence time, and hence increase the period of contact with the nasal mucosa and enhance the drug absorption. It is most certain that the high viscosity of hydrogel-based nanosystems can efficiently offer this mucoadhesive property. This update review discusses the possible benefits of using hydrogel polymer-based nanoparticles and hydrogel nanocomposites for drug/vaccine delivery through the intranasal administration.

  17. Cationic Polybutyl Cyanoacrylate Nanoparticles for DNA Delivery

    Directory of Open Access Journals (Sweden)

    Jinghua Duan

    2009-01-01

    Full Text Available To enhance the intracellular delivery potential of plasmid DNA using nonviral vectors, we used polybutyl cyanoacrylate (PBCA and chitosan to prepare PBCA nanoparticles (NPs by emulsion polymerization and prepared NP/DNA complexes through the complex coacervation of nanoparticles with the DNA. The object of our work is to evaluate the characterization and transfection efficiency of PBCA-NPs. The NPs have a zeta potential of 25.53 mV at pH 7.4 and size about 200 nm. Electrophoretic analysis suggested that the NPs with positive charges could protect the DNA from nuclease degradation and cell viability assay showed that the NPs exhibit a low cytotoxicity to human hepatocellular carcinoma (HepG2 cells. Qualitative and quantitative analysis of transfection in HepG2 cells by the nanoparticles carrying plasmid DNA encoding for enhanced green fluorescent protein (EGFP-N1 was done by digital fluorescence imaging microscopy system and fluorescence-activated cell sorting (FACS. Qualitative results showed highly efficient expression of GFP that remained stable for up to 96 hours. Quantitative results from FACS showed that PBCA-NPs were significantly more effective in transfecting HepG2 cells after 72 hours postincubation. The results of this study suggested that PBCA-NPs have favorable properties for nonviral delivery.

  18. Characterization and anti-tumor effects of chondroitin sulfate-chitosan nanoparticles delivery system

    Science.gov (United States)

    Hu, Chieh-Shen; Tang, Sung-Ling; Chiang, Chiao-Hsi; Hosseinkhani, Hossein; Hong, Po-Da; Yeh, Ming-Kung

    2014-11-01

    We prepared chondroitin sulfate (ChS)-chitosan (CS) nanoparticles (NPs) as a delivery carrier, and doxorubicin (Dox) was used as a model drug. The physicochemical properties and biological activities of the Dox-ChS-CS NPs including the release profile, cell cytotoxicity, cellular internalization, and in vivo anti-tumor effects were evaluated. The ChS-CS NPs and Dox-ChS-CS NPs had a mean size of 262.0 ± 15.0 and 369.4 ± 77.4 nm, and a zeta potential of 30.2 ± 0.9 and 20.6 ± 3.1 mV, respectively. In vitro release tests showed that the 50 % release time for the Dox-ChS-CS NPs was 20 h. Two hepatoma cell models, HepG2 and HuH6, were used for evaluating the cytotoxicity and cell uptake efficiency of the Dox-ChS-CS NPs. A significant difference was observed between doxorubicin solution and the Dox-ChS-CS NPs in the cellular uptake within 60 min ( p < 0.01). For the in vivo human xenograft-nude mouse model, the Dox-ChS-CS NPs were more effective with less body weight loss and anti-tumor growth suppression in comparison with the Dox solution. The prepared Dox-ChS-CS NPs offer a new effective targeting nanoparticle delivery system platform for anti-tumor therapy.

  19. A Promising Combo Gene Delivery System Developed from (3-Aminopropyl)triethoxysilane-Modified Iron Oxide Nanoparticles and Cationic Polymers

    Science.gov (United States)

    Zhang, Zubin; Song, Lina; Dong, Jinlai; Guo, Dawei; Du, Xiaolin; Cao, Biyin; Zhang, Yu; Gu, Ning; Mao, Xinliang

    2013-05-01

    (3-Aminopropyl)triethoxysilane-modified iron oxide nanoparticles (APTES-IONPs) have been evaluated for various biomedical applications, including medical imaging and drug delivery. Cationic polymers (CPs) such as Lipofectamine and TurboFect are widely used for research in gene delivery, but their toxicity and low in vivo efficiency limited their further application. In the present study, we synthesized water-soluble APTES-IONPs and developed a combo gene delivery system based on APTES-IONPs and CPs. This system significantly increased gene-binding capacity, protected genes from degradation, and improved gene transfection efficiency for DNA and siRNA in both adherent and suspension cells. Because of its great biocompatibility, high gene-carrying ability, and very low cytotoxicity, this combo gene delivery system will be expected for a wide application, and it might provide a new method for gene therapy.

  20. A Promising Combo Gene Delivery System Developed from (3-Aminopropyl)triethoxysilane-Modified Iron Oxide Nanoparticles and Cationic Polymers

    International Nuclear Information System (INIS)

    Zhang Zubin; Song Lina; Dong Jinlai; Guo Dawei; Du Xiaolin; Cao Biyin; Zhang Yu; Gu Ning; Mao Xinliang

    2013-01-01

    (3-Aminopropyl)triethoxysilane-modified iron oxide nanoparticles (APTES-IONPs) have been evaluated for various biomedical applications, including medical imaging and drug delivery. Cationic polymers (CPs) such as Lipofectamine and TurboFect are widely used for research in gene delivery, but their toxicity and low in vivo efficiency limited their further application. In the present study, we synthesized water-soluble APTES-IONPs and developed a combo gene delivery system based on APTES-IONPs and CPs. This system significantly increased gene-binding capacity, protected genes from degradation, and improved gene transfection efficiency for DNA and siRNA in both adherent and suspension cells. Because of its great biocompatibility, high gene-carrying ability, and very low cytotoxicity, this combo gene delivery system will be expected for a wide application, and it might provide a new method for gene therapy.

  1. Solid lipid nanoparticles for pulmonary delivery of insulin.

    Science.gov (United States)

    Liu, Jie; Gong, Tao; Fu, Hualin; Wang, Changguang; Wang, Xiuli; Chen, Qian; Zhang, Qin; He, Qin; Zhang, Zhirong

    2008-05-22

    Growing attention has been given to the potential of pulmonary route as an alternative for non-invasive systemic delivery of therapeutic agents. In this study, novel nebulizer-compatible solid lipid nanoparticles (SLNs) for pulmonary drug delivery of insulin were developed by reverse micelle-double emulsion method. The influences of the amount of sodium cholate (SC) and soybean phosphatidylcholine (SPC) on the deposition properties of the nanoparticles were investigated. Under optimal conditions, the entrapment delivery (ED), respirable fraction (RF) and nebulization efficiency (NE) of SLNs could reach 96.53, 82.11 and 63.28%, respectively, and Ins-SLNs remained stable during nebulization. Fasting plasma glucose level was reduced to 39.41% and insulin level was increased to approximately 170 microIU/ml 4h after pulmonary administration of 20 IU/kg Ins-SLNs. A pharmacological bioavailability of 24.33% and a relative bioavailability of 22.33% were obtained using subcutaneous injection as a reference. Incorporating fluorescent-labelled insulin into SLNs, we found that the SLNs were effectively and homogeneously distributed in the lung alveoli. These findings suggested that SLNs could be used as a potential carrier for pulmonary delivery of insulin by improving both in vitro and in vivo stability as well as prolonging hypoglycemic effect, which inevitably resulted in enhanced bioavailability.

  2. Nanoparticles laden in situ gel for sustained ocular drug delivery

    Directory of Open Access Journals (Sweden)

    Himanshu Gupta

    2013-01-01

    Full Text Available Proper availability of drug on to corneal surface is a challenging task. However, due to ocular physiological barriers, conventional eye drops display poor ocular bioavailability of drugs (< 1%. To improve precorneal residence time and ocular penetration, earlier our group developed and evaluated in situ gel and nanoparticles for ocular delivery. In interest to evaluate the combined effect of in situ gel and nanoparticles on ocular retention, we combined them. We are the first to term this combination as "nanoparticle laden in situ gel", that is, poly lactic co glycolic acid nanoparticle incorporated in chitosan in situ gel for sparfloxacin ophthalmic delivery. The formulation was tested for various physicochemical properties. It showed gelation pH near pH 7.2. The observation of acquired gamma camera images showed good retention over the entire precorneal area for sparfloxacin nanoparticle laden in situ gel (SNG as compared to marketed formulation. SNG formulation cleared at a very slow rate and remained at corneal surface for longer duration as no radioactivity was observed in systemic circulation. The developed formulation was found to be better in combination and can go up to the clinical evaluation and application.

  3. Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

    Energy Technology Data Exchange (ETDEWEB)

    Mott, Brittney [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States); Thamake, Sanjay [Radio-Isotope Therapy of America Foundation (United States); Vishwanatha, Jamboor; Jones, Harlan P., E-mail: harlan.jones@unthsc.edu [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States)

    2013-05-15

    Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 {+-} 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-{gamma} cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

  4. Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

    International Nuclear Information System (INIS)

    Mott, Brittney; Thamake, Sanjay; Vishwanatha, Jamboor; Jones, Harlan P.

    2013-01-01

    Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 ± 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-γ cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

  5. Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

    Science.gov (United States)

    Mott, Brittney; Thamake, Sanjay; Vishwanatha, Jamboor; Jones, Harlan P.

    2013-05-01

    Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 ± 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-γ cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

  6. Chitosan nanoparticles as non-viral gene delivery systems: determination of loading efficiency.

    Science.gov (United States)

    Carrillo, Carolina; Suñé, Josep Maria; Pérez-Lozano, Pilar; García-Montoya, Encarna; Sarrate, Rocío; Fàbregas, Anna; Miñarro, Montserrat; Ticó, Josep Ramon

    2014-07-01

    Chitosan has been studied for use in particle delivery systems for therapeutic purposes, since one of its most important applications is as a non-viral vector in gene therapy. Due to its positive charge, it is capable of forming DNA complexes (polyplexes) obtained through several methods and with the property of protecting nucleic acids. Two methods for obtaining the nanoparticles of chitosan-nucleic acids are reported in this study: simple complexation (of depolymerized chitosan or of different chitosan salts with plasmid) and ionic gelation (by adsorption of plasmid in the nanoparticles or by encapsulation of plasmid into nanoparticles). The determination of the loading efficiency of chitosan nanoparticles with the plasmid is carried out by electrophoretic mobility of the samples on agarose gel. Furthermore, the nanoparticles have been characterized according to their morphology, size and surface charge using AFM, TEM, laser diffraction and dynamic light scattering techniques. The polyplexes obtained have been found to be spherical and nanometric in size (between 100-230nm) with a zeta potential between 37 and 48mV. Positive results have been obtained by agarose gel electrophoresis for all studied cases: a concentration of between 20 and 30μg/mL of chitosan salts is required while for the remaining chitosan samples studied, 100% loading efficiency does not occur until a concentration equal to 100μg/mL (regardless of previous depolymerisation and the method performed). Chitosan-plasmid nanocapsules have been obtained at the polymer concentrations worked with (between 0.025 and 0.2%). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  7. Chitosan-sodium lauryl sulfate nanoparticles as a carrier system for the in vivo delivery of oral insulin.

    Science.gov (United States)

    Elsayed, Amani; Al-Remawi, Mayyas; Qinna, Nidal; Farouk, Asim; Al-Sou'od, Khaldoun A; Badwan, Adnan A

    2011-09-01

    The present work explores the possibility of formulating an oral insulin delivery system using nanoparticulate complexes made from the interaction between biodegradable, natural polymer called chitosan and anionic surfactant called sodium lauryl sulfate (SLS). The interaction between chitosan and SLS was confirmed by Fourier transform infrared spectroscopy. The nanoparticles were prepared by simple gelation method under aqueous-based conditions. The nanoparticles were stable in simulated gastric fluids and could protect the encapsulated insulin from the GIT enzymes. Additionally, the in vivo results clearly indicated that the insulin-loaded nanoparticles could effectively reduce the blood glucose level in a diabetic rat model. However, additional formulation modifications are required to improve insulin oral bioavailability.

  8. Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies.

    Science.gov (United States)

    Cevher, Erdal; Salomon, Stefan K; Somavarapu, Satyanarayana; Brocchini, Steve; Alpar, H Oya

    2015-01-01

    Here, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239-405 nm; surface charge: +18 and +27 mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC-pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th1/Th2 response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination.

  9. Magnetite Nanoparticles Coated with Rifampicin and Chlortetracycline for Drug Delivery Applications

    International Nuclear Information System (INIS)

    Nadejde, Claudia; Ciurlica, Ecaterina Foca-nici; Creanga, Dorina; Carlescu, Aurelian; Badescu, Vasile

    2010-01-01

    Four types of biocompatible magnetic fluids based on superparamagnetic nanoparticles with Fe 3 O 4 cores were functionalized with antibiotics (rifampicin or chlortetracycline) as potential candidates for in vivo biomedical applications, such as magnetically controlled drug delivery. The synthesis consisted in coprecipitation of iron oxide in basic, as well as in acid medium, followed by the dispersion of the resulted magnetite nanoparticles in aqueous solution containing the antibiotic. The chosen method to prepare the magnetite-core/drug-shell systems avoided intermediate organic coating of the magnetic nanoparticles. Comparative analysis of the rheological features of the aqueous magnetic fluid samples was performed. The structural features of the coated magnetic particles were investigated by X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometry (VSM). Good crystallinity and adequate stability in time were evidenced. Drug delivery curves were spectrophotometrically provided.

  10. Magnetic core-shell nanoparticles for drug delivery by nebulization

    LENUS (Irish Health Repository)

    Verma, Navin Kumar

    2013-01-23

    AbstractBackgroundAerosolized therapeutics hold great potential for effective treatment of various diseases including lung cancer. In this context, there is an urgent need to develop novel nanocarriers suitable for drug delivery by nebulization. To address this need, we synthesized and characterized a biocompatible drug delivery vehicle following surface coating of Fe3O4 magnetic nanoparticles (MNPs) with a polymer poly(lactic-co-glycolic acid) (PLGA). The polymeric shell of these engineered nanoparticles was loaded with a potential anti-cancer drug quercetin and their suitability for targeting lung cancer cells via nebulization was evaluated.ResultsAverage particle size of the developed MNPs and PLGA-MNPs as measured by electron microscopy was 9.6 and 53.2 nm, whereas their hydrodynamic swelling as determined using dynamic light scattering was 54.3 nm and 293.4 nm respectively. Utilizing a series of standardized biological tests incorporating a cell-based automated image acquisition and analysis procedure in combination with real-time impedance sensing, we confirmed that the developed MNP-based nanocarrier system was biocompatible, as no cytotoxicity was observed when up to 100 mug\\/ml PLGA-MNP was applied to the cultured human lung epithelial cells. Moreover, the PLGA-MNP preparation was well-tolerated in vivo in mice when applied intranasally as measured by glutathione and IL-6 secretion assays after 1, 4, or 7 days post-treatment. To imitate aerosol formation for drug delivery to the lungs, we applied quercitin loaded PLGA-MNPs to the human lung carcinoma cell line A549 following a single round of nebulization. The drug-loaded PLGA-MNPs significantly reduced the number of viable A549 cells, which was comparable when applied either by nebulization or by direct pipetting.ConclusionWe have developed a magnetic core-shell nanoparticle-based nanocarrier system and evaluated the feasibility of its drug delivery capability via aerosol administration. This study has

  11. Magnetic manipulation of superparamagnetic nanoparticles in a microfluidic system for drug delivery applications

    International Nuclear Information System (INIS)

    Agiotis, L.; Theodorakos, I.; Samothrakitis, S.; Papazoglou, S.; Zergioti, I.; Raptis, Y.S.

    2016-01-01

    Magnetic nanoparticles (MNPs), such as superparamagnetic iron oxide nanoparticles (SPIONS), have attracted major interest, due to their small size and unique magnetic properties, for drug delivery applications. In this context, iron oxide nanoparticles of magnetite (Fe 3 O 4 ) (150 nm magnetic core diameter), were used as drug carriers, aiming to form a magnetically controlled nano-platform. The navigation capabilities of the iron oxide nanoparticles in a microfluidic channel were investigated by simulating the magnetic field and the magnetic force applied on the magnetic nanoparticles inside a microfluidic chip. The simulations have been performed using finite element method (ANSY’S software). The optimum setup which intends to simulate the magnetic navigation of the nanoparticles, by the use of MRI-type fields, in the human circulatory system, consists of two parallel permanent magnets to produce a homogeneous magnetic field, in order to ensure the maximum magnetization of the magnetic nanoparticles, an electromagnet for the induction of the magnetic gradients and the creation of the magnetic force and a microfluidic setup so as to simulate the blood flow inside the human blood vessels. The magnetization of the superparamagnetic nanoparticles and the consequent magnetic torque developed by the two permanent magnets, together with the mutual interactions between the magnetized nanoparticles lead to the creation of rhabdoid aggregates in the direction of the homogeneous field. Additionally, the magnetic gradients introduced by the operation of the electromagnet are capable of directing the aggregates, as a whole, to the desired direction. By removing the magnetic fields, the aggregates are disrupted, due to the super paramagnetic nature of the nanoparticles, avoiding thus the formation of undesired thrombosis. - Highlights: • Homogeneous field yields an aggregation of particles along the lines of the field. • Additional electromagnet field rotates the

  12. Magnetic manipulation of superparamagnetic nanoparticles in a microfluidic system for drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Agiotis, L.; Theodorakos, I.; Samothrakitis, S.; Papazoglou, S.; Zergioti, I.; Raptis, Y.S.

    2016-03-01

    Magnetic nanoparticles (MNPs), such as superparamagnetic iron oxide nanoparticles (SPIONS), have attracted major interest, due to their small size and unique magnetic properties, for drug delivery applications. In this context, iron oxide nanoparticles of magnetite (Fe{sub 3}O{sub 4}) (150 nm magnetic core diameter), were used as drug carriers, aiming to form a magnetically controlled nano-platform. The navigation capabilities of the iron oxide nanoparticles in a microfluidic channel were investigated by simulating the magnetic field and the magnetic force applied on the magnetic nanoparticles inside a microfluidic chip. The simulations have been performed using finite element method (ANSY’S software). The optimum setup which intends to simulate the magnetic navigation of the nanoparticles, by the use of MRI-type fields, in the human circulatory system, consists of two parallel permanent magnets to produce a homogeneous magnetic field, in order to ensure the maximum magnetization of the magnetic nanoparticles, an electromagnet for the induction of the magnetic gradients and the creation of the magnetic force and a microfluidic setup so as to simulate the blood flow inside the human blood vessels. The magnetization of the superparamagnetic nanoparticles and the consequent magnetic torque developed by the two permanent magnets, together with the mutual interactions between the magnetized nanoparticles lead to the creation of rhabdoid aggregates in the direction of the homogeneous field. Additionally, the magnetic gradients introduced by the operation of the electromagnet are capable of directing the aggregates, as a whole, to the desired direction. By removing the magnetic fields, the aggregates are disrupted, due to the super paramagnetic nature of the nanoparticles, avoiding thus the formation of undesired thrombosis. - Highlights: • Homogeneous field yields an aggregation of particles along the lines of the field. • Additional electromagnet field rotates the

  13. Thiolated chitosan nanoparticles as a delivery system for antisense therapy: evaluation against EGFR in T47D breast cancer cells

    Directory of Open Access Journals (Sweden)

    Talaei F

    2011-09-01

    Full Text Available Fatemeh Talaei1, Ebrahim Azizi2, Rassoul Dinarvand3, Fatemeh Atyabi31Novel Drug Delivery Systems Lab, 2Molecular Research Lab, Department of Pharmacology and Toxicology, 3Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranAbstract: Thiolated chitosan has high transfection and mucoadhesive properties. We investigated the potential of two recently synthesized polymers: NAC-C (N-acetyl cysteine-chitosan and NAP-C (N-acetyl penicillamine-chitosan in anticancer drug delivery targeting epidermal growth factor receptor (EGFR. Doxorubicin (DOX and antisense oligonucleotide (ASOND-loaded polymer nanoparticles were prepared in water by a gelation process. Particle characterization, drug loading, and drug release were evaluated. To verify drug delivery efficiency in vitro experiments on a breast cancer cell line (T47D were performed. EGFR gene and protein expression was analyzed by real time quantitative polymerase chain reaction and Western blotting, respectively. A loading percentage of 63% ± 5% for ASOND and 70% ± 5% for DOX was achieved. Drug release data after 15 hours showed that ASOND and DOX were completely released from chitosan-based particles while a lower and more sustained release of only 22% ± 8% was measured for thiolated particles. In a cytosol simulated release medium/reducing environment, such as found intracellularly, polymer-based nanoparticles dissociated, liberating approximately 50% of both active substances within 7 hours. ASOND-loaded polymer nanoparticles had higher stability and high mucoadhesive properties. The ASOND-loaded thiolated particles significantly suppressed EGFR gene expression in T47D cells compared with ASOND-loaded chitosan particles and downregulated EGFR protein expression in cells. This study could facilitate future investigations into the functionality of NAP-C and NAC-C polymers as an efficient ASOND delivery system in vitro and in vivo

  14. In vitro evaluation of paclitaxel loaded amorphous chitin nanoparticles for colon cancer drug delivery.

    Science.gov (United States)

    Smitha, K T; Anitha, A; Furuike, T; Tamura, H; Nair, Shantikumar V; Jayakumar, R

    2013-04-01

    Chitin and its derivatives have been widely used in drug delivery applications due to its biocompatible, biodegradable and non-toxic nature. In this study, we have developed amorphous chitin nanoparticles (150±50 nm) and evaluated its potential as a drug delivery system. Paclitaxel (PTX), a major chemotherapeutic agent was loaded into amorphous chitin nanoparticles (AC NPs) through ionic cross-linking reaction using TPP. The prepared PTX loaded AC NPs had an average diameter of 200±50 nm. Physico-chemical characterization of the prepared nanoparticles was carried out. These nanoparticles were proven to be hemocompatible and in vitro drug release studies showed a sustained release of PTX. Cellular internalization of the NPs was confirmed by fluorescent microscopy as well as by flow cytometry. Anticancer activity studies proved the toxicity of PTX-AC NPs toward colon cancer cells. These preliminary results indicate the potential of PTX-AC NPs in colon cancer drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. pH-sensitive degradable nanoparticles for highly efficient intracellular delivery of exogenous protein

    Directory of Open Access Journals (Sweden)

    Xu D

    2013-09-01

    Full Text Available Dan Xu,1 Fei Wu,1 Yinghui Chen,2,* Liangming Wei,3,* Weien Yuan1,* 1School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 2Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, 3Key Laboratory for Thin Film and Microfabrication of the Ministry of Education, Institute of Micro/Nano Science and Technology, Shanghai Jiao Tong University, Shanghai, People's Republic of China*These authors contributed equally to this workBackground: Encapsulating exogenous proteins into a nanosized particulate system for delivery into cells is a great challenge. To address this issue, we developed a novel nanoparticle delivery method that differs from the nanoparticles reported to date because its core was composed of cross-linked dextran glassy nanoparticles which had pH in endosome-responsive environment and the protein was loaded in the core of cross-linked dextran glassy nanoparticles.Methods: In this study, dextran in a poly(ethylene glycol aqueous two-phase system created a different chemical environment in which proteins were encapsulated very efficiently (84.3% and 89.6% for enhanced green fluorescent protein and bovine serum albumin, respectively by thermodynamically favored partition. The structures of the nanoparticles were confirmed by confocal laser scanning microscopy and scanning electron microscopy.Results: The nanoparticles had a normal size distribution and a mean diameter of 186 nm. MTT assays showed that the nanoparticles were nontoxic up to a concentration of 2000 µg/mL in human hepatocarcinoma cell line SMMC-7721, HeLa, and BRL-3A cells. Of note, confocal laser scanning microscopy studies showed that nanoparticles loaded with fluorescein isothiocyanate-bovine serum albumin were efficiently delivered and released proteins into the cytoplasm of HeLa cells. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that nanoparticles with a functional protein (apoptin efficiently induced

  16. Ultrasound-sensitive nanoparticle aggregates for targeted drug delivery.

    Science.gov (United States)

    Papa, Anne-Laure; Korin, Netanel; Kanapathipillai, Mathumai; Mammoto, Akiko; Mammoto, Tadanori; Jiang, Amanda; Mannix, Robert; Uzun, Oktay; Johnson, Christopher; Bhatta, Deen; Cuneo, Garry; Ingber, Donald E

    2017-09-01

    Here we describe injectable, ultrasound (US)-responsive, nanoparticle aggregates (NPAs) that disintegrate into slow-release, nanoscale, drug delivery systems, which can be targeted to selective sites by applying low-energy US locally. We show that, unlike microbubble based drug carriers which may suffer from stability problems, the properties of mechanical activated NPAs, composed of polymer nanoparticles, can be tuned by properly adjusting the polymer molecular weight, the size of the nanoparticle precursors as well as the percentage of excipient utilized to hold the NPA together. We then apply this concept to practice by fabricating NPAs composed of nanoparticles loaded with Doxorubicin (Dox) and tested their ability to treat tumors via ultrasound activation. Mouse studies demonstrated significantly increased efficiency of tumor targeting of the US-activated NPAs compared to PLGA nanoparticle controls (with or without US applied) or intact NPAs. Importantly, when the Dox-loaded NPAs were injected and exposed to US energy locally, this increased ability to concentrate nanoparticles at the tumor site resulted in a significantly greater reduction in tumor volume compared to tumors treated with a 20-fold higher dose of the free drug. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Development of lattice-inserted 5-Fluorouracil-hydroxyapatite nanoparticles as a chemotherapeutic delivery system.

    Science.gov (United States)

    Tseng, Ching-Li; Chen, Jung-Chih; Wu, Yu-Chun; Fang, Hsu-Wei; Lin, Feng-Huei; Tang, Tzu-Piao

    2015-10-01

    dehydrogenase assay revealed that 5-Fluorouracil-hydroxyapatite was highly toxic to A549 cells through direct culture, this phenomenon may result from lysosomal decomposition of particles causing 5-Fluorouracil releasing. The pH-responsive hydroxyapatite-5-Fluorouracil nanoparticles have the potential to be part of a selective drug-delivery system in chemotherapy for cancer treatment. © The Author(s) 2015.

  18. Development and characterization of glutathione-conjugated albumin nanoparticles for improved brain delivery of hydrophilic fluorescent marker.

    Science.gov (United States)

    Patel, Prerak J; Acharya, Niyati S; Acharya, Sanjeev R

    2013-01-01

    The glutathione-conjugated bovine serum albumin (BSA) nanoparticles were constructed in the present exploration as a novel biodegradable carrier for brain-specific drug delivery with evaluation of its in vitro and in vivo delivery properties. BSA nanocarriers were activated and conjugated to the distal amine functions of the glutathione via carbodiimide chemistry using EDAC as a mediator. These nanoparticles were characterized for particle shape, average size, SPAN value, drug entrapment and in vitro drug release. Further, presence of glutathione on the surface of BSA nanoparticles was confirmed by Ellman's assay, which has suggested that approximately 750 units of glutathione were conjugated per BSA nanoparticle. To evaluate the brain delivery properties of the glutathione-conjugated BSA nanoparticles fluorescein sodium was used as a model hydrophilic compound. Permeability and neuronal uptake properties of developed formulations were evaluated against the MDCK-MDR1 endothelial and neuro-glial cells, respectively. The permeability of glutathione-conjugated BSA nanoparticles across the monolayer of MDCK-MDR1 endothelial tight junction was shown significantly higher than that of unconjugated nanoparticles and fluorescein sodium solution. Similarly, glutathione-conjugated nanoparticles exhibited considerably higher uptake by neuro-glial cells which was inferred by high fluorescence intensity under microscope in comparison to unconjugated nanoparticles and fluorescein sodium solution. Following an intravenous administration, nearly three folds higher fluorescein sodium was carried to the rat brain by glutathione-conjugated nanoparticles as compared to unconjugated nanoparticles. The significant in vitro and in vivo results suggest that glutathione-conjugated BSA nanoparticles is a promising brain drug delivery system with low toxicity.

  19. Synthesis of PLGA-Lipid Hybrid Nanoparticles for siRNA Delivery Using the Emulsion Method PLGA-PEG-Lipid Nanoparticles for siRNA Delivery.

    Science.gov (United States)

    Wang, Lei; Griffel, Benjamin; Xu, Xiaoyang

    2017-01-01

    The effective delivery of small interfering RNA (siRNA) to tumor cells remains a challenge for applications in cancer therapy. The development of polymeric nanoparticles with high siRNA loading efficacy has shown great potential for cancer targets. Double emulsion solvent evaporation technique is a useful tool for encapsulation of hydrophilic molecules (e.g., siRNA). Here we describe a versatile platform for siRNA delivery based on PLGA-PEG-cationic lipid nanoparticles by using the double emulsion method. The resulting nanoparticles show high encapsulation efficiency for siRNA (up to 90%) and demonstrate effective downregulation of the target genes in vitro and vivo.

  20. Lipid nanoparticles for the delivery of poorly water-soluble drugs.

    Science.gov (United States)

    Bunjes, Heike

    2010-11-01

    This review discusses important aspects of lipid nanoparticles such as colloidal lipid emulsions and, in particular, solid lipid nanoparticles as carrier systems for poorly water-soluble drugs, with a main focus on the parenteral and peroral use of these carriers. A short historical background of the development of colloidal lipid emulsions and solid lipid nanoparticles is provided and their similarities and differences are highlighted. With regard to drug incorporation, parameters such as the chemical nature of the particle matrix and the physicochemical nature of the drug, effects of drug partition and the role of the particle interface are discussed. Since, because of the crystalline nature of their lipid core, solid lipid nanoparticles display some additional important features compared to emulsions, their specificities are introduced in more detail. This mainly includes their solid state behaviour (crystallinity, polymorphism and thermal behaviour) and the consequences of their usually non-spherical particle shape. Since lipid nanoemulsions and -suspensions are also considered as potential means to alter the pharmacokinetics of incorporated drug substances, some underlying basic considerations, in particular concerning the drug-release behaviour of such lipid nanodispersions on dilution, are addressed as well. Colloidal lipid emulsions and solid lipid nanoparticles are interesting options for the delivery of poorly water-soluble drug substances. Their specific physicochemical properties need, however, to be carefully considered to provide a rational basis for their development into effective carrier systems for a given delivery task. © 2010 The Author. Journal compilation © 2010 Royal Pharmaceutical Society of Great Britain.

  1. Functionalized nanoparticles for AMF-induced gene and drug delivery

    Science.gov (United States)

    Biswas, Souvik

    non-toxic magnetoplexes (magnetic nanoparticle + pDNA complex) derived from dMLP deliver pDNA into mammalian cells even without external magnetic assistance. To date, dMLP is the only polymer-free magnetic gene delivery system that can deliver pDNA without any magnetic assistance. Chapter 3 of this thesis outlines the synthesis and characterization of other oxime ether lipids and details studies using derived-lipoplexes. These lipids were evaluated in pDNA and siRNA transfection studies in various mammalian cell lines. This work constitutes the first use of an oxime ether as the linking domain in cationic transfection lipids. These biocompatible oxime ether lipids can be readily assembled by click chemistry through ligation of hydrophobic aldehydes with quaternary ammonium aminooxy salts. Our studies showed that the oxime ether lipids transfected pDNA and siRNA efficiently in MCF-7, H 1792, and in PAR C10 cells comparable to and in some cases better than commercial transfection lipids. Chapter 4 describes the design and characterization of a nano-magnetic delivery system for AMF-induced drug (doxorubicin) release. In efforts to develop a magnetic formulation free from thermosensitive materials, such as hydrogels, we synthesized three nanoparticle-based doxorubicin formulations using charge interactions as the key associative force. To do so, we synthesized and characterized a novel cationic oxime ether conjugate at C-13 of doxorubicin. Our investigation indicated that the positive charge of the oxime ether drug conjugate tended to bind better to the negatively charged nanoparticle than did the other formulations prepared in stepwise manner. Our findings show that the nano-magnetic formulations remained essestially inactive at body temperature (37.5 °C) and released a majority of the cargo only when exposed to an external AMF. Our designed magnetic drug delivery platform is the first example of an AMF-inducible system that does not depend on the inclusion of

  2. In vitro cytotoxicity and phototoxicity of surface-modified gold nanoparticles associated with neutral red as a potential drug delivery system in phototherapy

    Energy Technology Data Exchange (ETDEWEB)

    Verissimo, Tanira V. [School of Health Sciences, University of Brasilia, Brasilia (Brazil); Laboratory of Photochemistry and Nanobiotechnology, Faculty of Ceilandia, University of Brasilia, Brasilia (Brazil); Santos, Naiara T. [School of Health Sciences, University of Brasilia, Brasilia (Brazil); Silva, Jaqueline R.; Azevedo, Ricardo B. [Institute of Biological Sciences, University of Brasilia, Brasilia (Brazil); Gomes, Anderson J., E-mail: ajgomes@unb.br [School of Health Sciences, University of Brasilia, Brasilia (Brazil); Laboratory of Photochemistry and Nanobiotechnology, Faculty of Ceilandia, University of Brasilia, Brasilia (Brazil); Lunardi, Claure N., E-mail: clunardi@unb.br [School of Health Sciences, University of Brasilia, Brasilia (Brazil); Laboratory of Photochemistry and Nanobiotechnology, Faculty of Ceilandia, University of Brasilia, Brasilia (Brazil)

    2016-08-01

    The surface of gold nanoparticles (AuNP) was modified, improving their interaction with neutral red (NR), by using sodium thioglycolate (TGA) as a covering agent. The resulting NR-AuNPTGA system was evaluated as a potential drug delivery system for photodynamic therapy (PDT). The associations of NR with the gold nanoparticles were evaluated using UV-vis spectrometry and measurement of their zeta potential and size distribution. The toxicity and phototoxicity of NR, AuNPTGA and NR-AuNPTGA were evaluated in NIH-3T3 fibroblast and 4T1 tumor cell lines. The compounds NR and NR-AuNPTGA induced toxicity in 4T1 tumor cells and NIH-3T3 fibroblasts under visible light irradiation. Modification of the surface of AuNP with TGA prevented nanoparticle aggregation and allowed greater association with NR molecules than for naked AuNP. The photosensitizer (PS) characteristics were not affected by its association with the modified surface of the gold nanoparticles, leading to a reduction of cell viability in both cell lines assayed. This NR-AuNPTGA system is a promising drug delivery system for photodynamic cancer therapy. - Highlights: • Modified gold nanoparticle (AuNP) by sodium thioglicolate (TGA) prevents aggregation. • Neutral red (NR) adsorbed on the surface of modified gold nanoparticles (AuNPTGA). • AuNPTGA is suitable as a platform to deliver the NR under irradiation process. • Photodamage of 90% was achieved by NR added to AuNPTGA in 4T1 and NIH-3T3 cells.

  3. Drug delivery into microneedle-porated nails from nanoparticle reservoirs.

    Science.gov (United States)

    Chiu, Wing Sin; Belsey, Natalie A; Garrett, Natalie L; Moger, Julian; Price, Gareth J; Delgado-Charro, M Begoña; Guy, Richard H

    2015-12-28

    This study demonstrates the potential of polymeric nanoparticles as drug reservoirs for sustained topical drug delivery into microneedle-treated human nail. Laser scanning confocal microscopy was used to image the delivery of a fluorescent model compound from nanoparticles into the nail. A label-free imaging technique, stimulated Raman scattering microscopy, was applied, in conjunction with two-photon fluorescence imaging, to probe the disposition of nanoparticles and an associated lipophilic 'active' in a microneedle-porated nail. The results provide clear evidence that the nanoparticles function as immobile reservoirs, sequestered on the nail surface and in the microneedle-generated pores, from which the active payload can be released and diffuse laterally into the nail over an extended period of time. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. The role of chitosan on oral delivery of peptide-loaded nanoparticle formulation.

    Science.gov (United States)

    Wong, Chun Y; Al-Salami, Hani; Dass, Crispin R

    2017-12-01

    Therapeutic peptides are conventionally administered via subcutaneous injection. Chitosan-based nanoparticles are gaining increased attention for their ability to serve as a carrier for oral delivery of peptides and vaccination. They offered superior biocompatibiltiy, controlled drug release profile and facilitated gastrointestinal (GI) absorption. The encapsulated peptides can withstand enzymatic degradation and various pH. Chitosan-based nanoparticles can also be modified by ligand conjugation to the surface of nanoparticle for transcellular absorption and specific-targeted delivery of macromolecules to the tissue of interest. Current research suggests that chitosan-based nanoparticles can deliver therapeutic peptide for the treatment of several medical conditions such as diabetes, bacterial infection and cancer. This review summarises the role of chitosan in oral nanoparticle delivery and identifies the clinical application of peptide-loaded chitosan-based nanoparticles.

  5. Gold nanoparticle trapping and delivery for therapeutic applications

    Directory of Open Access Journals (Sweden)

    Aziz MS

    2011-12-01

    Full Text Available MS Aziz1, Nathaporn Suwanpayak3,4, Muhammad Arif Jalil2, R Jomtarak4, T Saktioto2, Jalil Ali1, PP Yupapin41Institute of Advanced Photonics Science, 2Ibnu Sina Institute of Fundamental Science Studies, Nanotechnology Research Alliance, Universiti Teknologi Malaysia, Johor Bahru, Malaysia; 3King Mongkut's Institute of Technology Ladkrabang, Chump on Campus, Chumphon, 4Nanoscale Science and Engineering Research Alliance (N'SERA, Faculty of Science, King Mongkut's Institute of Technology Ladkrabang, Bangkok, ThailandAbstract: A new optical trapping design to transport gold nanoparticles using a PANDA ring resonator system is proposed. Intense optical fields in the form of dark solitons controlled by Gaussian pulses are used to trap and transport nanoscopic volumes of matter to the desired destination via an optical waveguide. Theoretically, the gradient and scattering forces are responsible for this trapping phenomenon, where in practice such systems can be fabricated and a thin-film device formed on the specific artificial medical materials, for instance, an artificial bone. The dynamic behavior of the tweezers can be tuned by controlling the optical pulse input power and parameters of the ring resonator system. Different trap sizes can be generated to trap different gold nanoparticles sizes, which is useful for gold nanoparticle therapy. In this paper, we have shown the utility of gold nanoparticle trapping and delivery for therapy, which may be useful for cosmetic therapy and related applications.Keywords: gold nanoparticle trapping, particle trapping, therapy, transport

  6. Formulation design for target delivery of iron nanoparticles to TCE zones.

    Science.gov (United States)

    Wang, Ziheng; Acosta, Edgar

    2013-12-01

    Nanoparticles of zero-valent iron (NZVI) are effective reducing agents for some dense non-aqueous phase liquid (DNAPL) contaminants such as trichloroethylene (TCE). However, target delivery of iron nanoparticles to DNAPL zones in the aquifer remains an elusive feature for NZVI technologies. This work discusses three strategies to deliver iron nanoparticles to DNAPL zones. To this end, iron oxide nanoparticles coated with oleate (OL) ions were used as stable analogs for NZVI. The OL-coated iron oxide nanoparticles are rendered lipophilic via (a) the addition of CaCl2, (b) acidification, or (c) the addition of a cationic surfactant, benzethonium chloride (BC). Mixtures of OL and BC show promise as a target delivery strategy due to the high stability of the nanoparticles in water, and their preferential partition into TCE in batch experiments. Column tests show that while the OL-BC coated iron oxide nanoparticles remain largely mobile in TCE-free columns, a large fraction of these particles are retained in TCE-contaminated columns, confirming the effectiveness of this target delivery strategy. © 2013.

  7. Peptide and protein delivery using new drug delivery systems.

    Science.gov (United States)

    Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K

    2013-01-01

    Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery.

  8. Mesoporous silica nanoparticles as a biomolecule delivery vehicle in plants

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, Hashmath I., E-mail: hashmath.i@deakin.edu.au [Deakin University, Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences (Australia); Yi, Zhifeng [Deakin University, Institute for Frontier Materials (Australia); Rookes, James E. [Deakin University, Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences (Australia); Kong, Lingxue X. [Deakin University, Institute for Frontier Materials (Australia); Cahill, David M. [Deakin University, Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences (Australia)

    2013-06-15

    We report the uptake by wheat, lupin and Arabidopsis of mesoporous silica nanoparticles functionalised with amine cross-linked fluorescein isothiocyanate (MSN-APTES-FITC). The preparation of these particles at room temperature enabled the synthesis of 20 nm particles that contained a network of interconnected pores around 2 nm in diameter. The uptake and distribution of these nanoparticles were examined during seed germination, in roots of plants grown in a hydroponic system and in whole leaves and roots of plants via vacuum infiltration. The nanoparticles did not affect seed germination in lupin and there was no phytotoxicity. Following germination of wheat and lupin grown in a nutrient solution containing nanoparticles, they were found within cells and cell walls of the emerging root and in the vascular transport elements, the xylem, and in other associated cells. In leaves and roots of Arabidopsis the nanoparticles were found, following vacuum infiltration of whole seedlings, to be taken up by the entire leaf and they were principally found in the intercellular spaces of the mesophyll but also throughout much of the root system. We propose that MSNs could be used as a novel delivery system for small molecules in plants.

  9. Highly Efficient Intracellular Protein Delivery by Cationic Polyethyleneimine-Modified Gelatin Nanoparticles

    Directory of Open Access Journals (Sweden)

    Ming-Ju Chou

    2018-02-01

    Full Text Available Intracellular protein delivery may provide a safe and non-genome integrated strategy for targeting abnormal or specific cells for applications in cell reprogramming therapy. Thus, highly efficient intracellular functional protein delivery would be beneficial for protein drug discovery. In this study, we generated a cationic polyethyleneimine (PEI-modified gelatin nanoparticle and evaluated its intracellular protein delivery ability in vitro and in vivo. The experimental results showed that the PEI-modified gelatin nanoparticle had a zeta potential of approximately +60 mV and the particle size was approximately 135 nm. The particle was stable at different biological pH values and temperatures and high protein loading efficiency was observed. The fluorescent image results revealed that large numbers of particles were taken up into the mammalian cells and escaped from the endosomes into the cytoplasm. In a mouse C26 cell-xenograft cancer model, particles accumulated in cancer cells. In conclusion, the PEI-modified gelatin particle may provide a biodegradable and highly efficient protein delivery system for use in regenerative medicine and cancer therapy.

  10. Dual drug-loaded nanoparticles on self-integrated scaffold for controlled delivery

    Directory of Open Access Journals (Sweden)

    Bennet D

    2012-07-01

    Full Text Available Devasier Bennet,1 Mohana Marimuthu,1 Sanghyo Kim,1 Jeongho An21Department of Bionanotechnology, Gachon University, Gyeonggi, Republic of Korea; 2Department of Polymer Science and Engineering, SunKyunKwan University, Gyeonggi, Republic of KoreaAbstract: Antioxidant (quercetin and hypoglycemic (voglibose drug-loaded poly-D,L-lactide-co-glycolide nanoparticles were successfully synthesized using the solvent evaporation method. The dual drug-loaded nanoparticles were incorporated into a scaffold film using a solvent casting method, creating a controlled transdermal drug-delivery system. Key features of the film formulation were achieved utilizing several ratios of excipients, including polyvinyl alcohol, polyethylene glycol, hyaluronic acid, xylitol, and alginate. The scaffold film showed superior encapsulation capability and swelling properties, with various potential applications, eg, the treatment of diabetes-associated complications. Structural and light scattering characterization confirmed a spherical shape and a mean particle size distribution of 41.3 nm for nanoparticles in the scaffold film. Spectroscopy revealed a stable polymer structure before and after encapsulation. The thermoresponsive swelling properties of the film were evaluated according to temperature and pH. Scaffold films incorporating dual drug-loaded nanoparticles showed remarkably high thermoresponsivity, cell compatibility, and ex vivo drug-release behavior. In addition, the hybrid film formulation showed enhanced cell adhesion and proliferation. These dual drug-loaded nanoparticles incorporated into a scaffold film may be promising for development into a transdermal drug-delivery system.Keywords: quercetin, voglibose, biocompatible materials, encapsulation, transdermal

  11. Poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped trans-cinnamaldehyde and eugenol for antimicrobial delivery applications.

    Science.gov (United States)

    Gomes, Carmen; Moreira, Rosana G; Castell-Perez, Elena

    2011-03-01

    Eugenol and trans-cinnamaldehyde are natural compounds known to be highly effective antimicrobials; however, both are hydrophobic molecules, a limitation to their use within the food industry. The goal of this study was to synthesize spherical poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped eugenol and trans-cinnamaldehyde for future antimicrobial delivery applications. The emulsion evaporation method was used to form the nanoparticles in the presence of poly (vinyl alcohol) (PVA) as a surfactant. The inclusion of antimicrobial compounds into the PLGA nanoparticles was accomplished in the organic phase. Synthesis was followed by ultrafiltration (performed to eliminate the excess of PVA and antimicrobial compound) and freeze-drying. The nanoparticles were characterized by their shape, size, entrapment efficiency, and antimicrobial efficiency. The entrapment efficiency for eugenol and trans-cinnamaldehyde was approximately 98% and 92%, respectively. Controlled release experiments conducted in vitro at 37 °C and 100 rpm for 72 h showed an initial burst followed by a slower rate of release of the antimicrobial entrapped inside the PLGA matrix. All loaded nanoparticles formulations proved to be efficient in inhibiting growth of Salmonella spp. (Gram-negative bacterium) and Listeria spp. (Gram-positive bacterium) with concentrations ranging from 20 to 10 mg/mL. Results suggest that the application of these antimicrobial nanoparticles in food systems may be effective at inhibiting specific pathogens. Nanoencapsulation of lipophilic antimicrobial compounds has great potential for improving the effectiveness and efficiency of delivery in food systems. This study consisted of synthesizing PLGA nanoparticles with entrapped eugenol and trans-cinnamaldehyde. By characterizing these new delivery systems, one can understand the controlled-release mechanism and antimicrobial efficiency that provides a foundation that will enable food manufacturers to design

  12. Targeted chimera delivery to ovarian cancer cells by heterogeneous gold magnetic nanoparticle

    Science.gov (United States)

    Chen, Yao; Xu, Mengjiao; Guo, Yi; Tu, Keyao; Wu, Weimin; Wang, Jianjun; Tong, Xiaowen; Wu, Wenjuan; Qi, Lifeng; Shi, Donglu

    2017-01-01

    Efficient delivery of small interfering RNAs (siRNAs) to the targeted cells has remained a significant challenge in clinical applications. In the present study, we developed a novel aptamer-siRNA chimera delivery system mediated by cationic Au-Fe3O4 nanoparticles (NPs). The chimera constructed by VEGF RNA aptamer and Notch3 siRNA was bonded with heterogeneous Au-Fe3O4 nanoparticles by electrostatic interaction. The obtained complex exhibited much higher silencing efficiency against Notch3 gene compared with chimera alone and lipofectamine-siRNA complex, and improved the antitumor effects of the loaded chimera. Moreover, the efficient delivery of the chimera by Au-Fe3O4 NPs could reverse multi-drug resistance (MDR) of ovarian cancer cells against the chemotherapeutic drug cisplatin, indicating its potential capability for future targeted cancer therapy while overcoming MDR.

  13. Nanoparticles laden in situ gelling system for ocular drug targeting

    Directory of Open Access Journals (Sweden)

    Divya Kumar

    2013-01-01

    Full Text Available Designing an ophthalmic drug delivery system is one of the most difficult challenges for the researchers. The anatomy and physiology of eye create barriers like blinking which leads to the poor retention time and penetration of drug moiety. Some conventional ocular drug delivery systems show shortcomings such as enhanced pre-corneal elimination, high variability in efficiency, and blurred vision. To overcome these problems, several novel drug delivery systems such as liposomes, nanoparticles, hydrogels, and in situ gels have been developed. In situ-forming hydrogels are liquid upon instillation and undergo phase transition in the ocular cul-de-sac to form viscoelastic gel and this provides a response to environmental changes. In the past few years, an impressive number of novel temperature, pH, and ion-induced in situ-forming systems have been reported for sustain ophthalmic drug delivery. Each system has its own advantages and drawbacks. Thus, a combination of two drug delivery systems, i.e., nanoparticles and in situ gel, has been developed which is known as nanoparticle laden in situ gel. This review describes every aspects of this novel formulation, which present the readers an exhaustive detail and might contribute to research and development.

  14. Magnetic nanoparticles for a new drug delivery system to control quercetin releasing for cancer chemotherapy

    International Nuclear Information System (INIS)

    Barreto, A. C. H.; Santiago, V. R.; Mazzetto, S. E.; Denardin, J. C.; Lavín, R.; Mele, Giuseppe; Ribeiro, M. E. N. P.; Vieira, Icaro G. P.; Gonçalves, Tamara; Ricardo, N. M. P. S.

    2011-01-01

    Quercetin belongs to the chemical class of flavonoids and can be found in many common foods, such as apples, nuts, berries, etc. It has been demonstrated that quercetin has a wide array of biological effects that are considered beneficial to health treatment, mainly as anticancer. However, therapeutic applications of quercetin have been restricted to oral administration due to its sparing solubility in water and instability in physiological medium. A drug delivery methodology was proposed in this work to study a new quercetin release system in the form of magnetite–quercetin–copolymer (MQC). These materials were characterized through XRD, TEM, IR, and Thermal analysis. In addition, the magnetization curves and quercetin releasing experiments were performed. It was observed a nanoparticle average diameter of 11.5 and 32.5 nm at Fe 3 O 4 and MQC, respectively. The presence of magnetic nanoparticles in this system offers the promise of targeting specific organs within the body. These results indicate the great potential for future applications of the MQC to be used as a new quercetin release system.

  15. Nanoparticles for intracellular-targeted drug delivery

    International Nuclear Information System (INIS)

    Paulo, Cristiana S O; Pires das Neves, Ricardo; Ferreira, Lino S

    2011-01-01

    Nanoparticles (NPs) are very promising for the intracellular delivery of anticancer and immunomodulatory drugs, stem cell differentiation biomolecules and cell activity modulators. Although initial studies in the area of intracellular drug delivery have been performed in the delivery of DNA, there is an increasing interest in the use of other molecules to modulate cell activity. Herein, we review the latest advances in the intracellular-targeted delivery of short interference RNA, proteins and small molecules using NPs. In most cases, the drugs act at different cellular organelles and therefore the drug-containing NPs should be directed to precise locations within the cell. This will lead to the desired magnitude and duration of the drug effects. The spatial control in the intracellular delivery might open new avenues to modulate cell activity while avoiding side-effects.

  16. Iron oxide nanoparticles for magnetically-guided and magnetically-responsive drug delivery.

    Science.gov (United States)

    Estelrich, Joan; Escribano, Elvira; Queralt, Josep; Busquets, Maria Antònia

    2015-04-10

    In this review, we discuss the recent advances in and problems with the use of magnetically-guided and magnetically-responsive nanoparticles in drug delivery and magnetofection. In magnetically-guided nanoparticles, a constant external magnetic field is used to transport magnetic nanoparticles loaded with drugs to a specific site within the body or to increase the transfection capacity. Magnetofection is the delivery of nucleic acids under the influence of a magnetic field acting on nucleic acid vectors that are associated with magnetic nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles are encapsulated or embedded in a larger colloidal structure that carries a drug. In this last case, an alternating magnetic field can modify the structure of the colloid, thereby providing spatial and temporal control over drug release.

  17. The Chemistry of Bioconjugation in Nanoparticles-Based Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Karolina Werengowska-Ciećwierz

    2015-01-01

    Full Text Available Nanomedicine is, generally, the application of nanotechnology to medicine. The term nanomedicine includes monitoring, construction of novel drug delivery systems, and any possible future applications of nanotechnology and nanovaccinology. In this review, the most important ligand-nanocarrier and drug-nanocarrier bioconjugations are described. The detailed characterizations of covalently formed bonds between targeted ligand and nanocarrier, including amide, thioether, disulfide, acetyl-hydrazone and polycyclic groups, are described. Also, the coupling of small elements and heteroatoms in the form of R-X-R the “click chemistry” groups is shown. Physical adsorption and chemical bonding of drug to nanocarrier surface involving drug on the internal or external surfaces of nanocarriers are described throughout possibility of the formation of the above-mentioned functionalities. Moreover, the most popular nanostructures (liposomes, micelles, polymeric nanoparticles, dendrimers, carbon nanotubes, and nanohorns are characterized as nanocarriers. Building of modern drug carrier is a new method which could be effectively applied in targeted anticancer therapy.

  18. Doxorubicin loaded PVA coated iron oxide nanoparticles for targeted drug delivery

    International Nuclear Information System (INIS)

    Kayal, S.; Ramanujan, R.V.

    2010-01-01

    Magnetic drug targeting is a drug delivery system that can be used in locoregional cancer treatment. Coated magnetic particles, called carriers, are very useful for delivering chemotherapeutic drugs. Magnetic carriers were synthesized by coprecipitation of iron oxide followed by coating with polyvinyl alcohol (PVA). Characterization was carried out using X-ray diffraction, TEM, TGA, FTIR and VSM techniques. The magnetic core of the carriers was magnetite (Fe 3 O 4 ), with average size of 10 nm. The room temperature VSM measurements showed that magnetic particles were superparamagnetic. The amount of PVA bound to the iron oxide nanoparticles were estimated by thermogravimetric analysis (TGA) and the attachment of PVA to the iron oxide nanoparticles was confirmed by FTIR analysis. Doxorubicin (DOX) drug loading and release profiles of PVA coated iron oxide nanoparticles showed that up to 45% of adsorbed drug was released in 80 h, the drug release followed the Fickian diffusion-controlled process. The binding of DOX to the PVA was confirmed by FTIR analysis. The present findings show that DOX loaded PVA coated iron oxide nanoparticles are promising for magnetically targeted drug delivery.

  19. Nanoparticles as safe and effective delivery systems of antifungal agents: Achievements and challenges.

    Science.gov (United States)

    Soliman, Ghareb M

    2017-05-15

    Invasive fungal infections are becoming a major health concern in several groups of patients leading to severe morbidity and mortality. Moreover, cutaneous fungal infections are a major cause of visits to outpatient dermatology clinics. Despite the availability of several effective agents in the antifungal drug arena, their therapeutic outcome is less than optimal due to limitations related to drug physicochemical properties and toxicity. For instance, poor aqueous solubility limits the formulation options and efficacy of several azole antifungal drugs while toxicity limits the benefits of many other drugs. Nanoparticles hold great promise to overcome these limitations due to their ability to enhance drug aqueous solubility, bioavailability and antifungal efficacy. Further, drug incorporation into nanoparticles could greatly reduce its toxicity. Despite these interesting nanoparticle features, there are only few marketed nanoparticle-based antifungal drug formulations. This review sheds light on different classes of nanoparticles used in antifungal drug delivery, such as lipid-based vesicles, polymeric micelles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and dendrimers with emphasis on their advantages and limitations. Translation of these nanoformulations from the lab to the clinic could be facilitated by focusing the research on overcoming problems related to nanoparticle stability, drug loading and high cost of production and standardization. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. 2011 Rita Schaffer lecture: nanoparticles for intracellular nucleic acid delivery.

    Science.gov (United States)

    Green, Jordan J

    2012-07-01

    Nanoparticles are a promising technology for delivery of new types of therapeutics. A polymer library approach has allowed engineering of polymeric particles that are particularly effective for the delivery of DNA and siRNA to human cells. Certain chemical structural motifs, degradable linkages, hydrophobicity, and biophysical properties are key for successful intracellular delivery. Small differences to biomaterial structure, and especially the type of degradable linkage in the polymers, can be critical for successful delivery of siRNA vs. DNA. Furthermore, subtle changes to biomaterial structure can facilitate cell-type gene delivery specificity between human brain cancer cells and healthy cells as well as between human retinal endothelial cells and epithelial cells. These polymeric nanoparticles are effective for nucleic acid delivery in a broad range of human cell types and have applications to regenerative medicine, ophthalmology, and cancer among many other biomedical research areas.

  1. Biopolymer-Based Nanoparticles for Drug/Gene Delivery and Tissue Engineering

    Science.gov (United States)

    Nitta, Sachiko Kaihara; Numata, Keiji

    2013-01-01

    There has been a great interest in application of nanoparticles as biomaterials for delivery of therapeutic molecules such as drugs and genes, and for tissue engineering. In particular, biopolymers are suitable materials as nanoparticles for clinical application due to their versatile traits, including biocompatibility, biodegradability and low immunogenicity. Biopolymers are polymers that are produced from living organisms, which are classified in three groups: polysaccharides, proteins and nucleic acids. It is important to control particle size, charge, morphology of surface and release rate of loaded molecules to use biopolymer-based nanoparticles as drug/gene delivery carriers. To obtain a nano-carrier for therapeutic purposes, a variety of materials and preparation process has been attempted. This review focuses on fabrication of biocompatible nanoparticles consisting of biopolymers such as protein (silk, collagen, gelatin, β-casein, zein and albumin), protein-mimicked polypeptides and polysaccharides (chitosan, alginate, pullulan, starch and heparin). The effects of the nature of the materials and the fabrication process on the characteristics of the nanoparticles are described. In addition, their application as delivery carriers of therapeutic drugs and genes and biomaterials for tissue engineering are also reviewed. PMID:23344060

  2. Biopolymer-Based Nanoparticles for Drug/Gene Delivery and Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Keiji Numata

    2013-01-01

    Full Text Available There has been a great interest in application of nanoparticles as biomaterials for delivery of therapeutic molecules such as drugs and genes, and for tissue engineering. In particular, biopolymers are suitable materials as nanoparticles for clinical application due to their versatile traits, including biocompatibility, biodegradability and low immunogenicity. Biopolymers are polymers that are produced from living organisms, which are classified in three groups: polysaccharides, proteins and nucleic acids. It is important to control particle size, charge, morphology of surface and release rate of loaded molecules to use biopolymer-based nanoparticles as drug/gene delivery carriers. To obtain a nano-carrier for therapeutic purposes, a variety of materials and preparation process has been attempted. This review focuses on fabrication of biocompatible nanoparticles consisting of biopolymers such as protein (silk, collagen, gelatin, β-casein, zein and albumin, protein-mimicked polypeptides and polysaccharides (chitosan, alginate, pullulan, starch and heparin. The effects of the nature of the materials and the fabrication process on the characteristics of the nanoparticles are described. In addition, their application as delivery carriers of therapeutic drugs and genes and biomaterials for tissue engineering are also reviewed.

  3. Aminoglycoside-derived amphiphilic nanoparticles for molecular delivery.

    Science.gov (United States)

    Miryala, Bhavani; Godeshala, Sudhakar; Grandhi, Taraka Sai Pavan; Christensen, Matthew D; Tian, Yanqing; Rege, Kaushal

    2016-10-01

    The development of effective drug carriers can lead to improved outcomes in a variety of disease conditions. Aminoglycosides have been used as antibacterial therapeutics, and are attractive as monomers for the development of polymeric materials in various applications. Here, we describe the development of novel aminoglycoside-derived amphiphilic nanoparticles for drug delivery, with an eye towards ablation of cancer cells. The aminoglycoside paromomycin was first cross-linked with resorcinol diglycidyl ether leading to the formation of a poly (amino ether), PAE. PAE molecules were further derivatized with methoxy-terminated poly(ethylene glycol) or mPEG resulting in the formation of mPEG-PAE polymer, which self-assembled to form nanoparticles. Formation of the mPEG-PAE amphiphile was characterized using (1)H NMR, (13)C NMR, gel permeation chromatography (GPC) and FTIR spectroscopy. Self-assembly of the polymer into nanoparticles was characterized using dynamic light scattering, zeta potential analyses, atomic force microscopy (AFM) and the pyrene fluorescence assay. mPEG-PAE nanoparticles were able to carry significant amounts of doxorubicin (DOX), presumably by means of hydrophobic interactions between the drug and the core. Cell-based studies indicated that mPEG-PAE nanoparticles, loaded with doxorubicin, were able to induce significant loss in viabilities of PC3 human prostate cancer, MDA-MB-231 human breast cancer, and MB49 murine bladder cancer cells; empty nanoparticles resulted in negligible losses of cell viability under the conditions investigated. Taken together, our results indicate that the mPEG-PAE nanoparticle platform is attractive for drug delivery in different applications, including cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Smart multifunctional drug delivery towards anticancer therapy harmonized in mesoporous nanoparticles

    Science.gov (United States)

    Baek, Seonmi; Singh, Rajendra K.; Khanal, Dipesh; Patel, Kapil D.; Lee, Eun-Jung; Leong, Kam W.; Chrzanowski, Wojciech; Kim, Hae-Won

    2015-08-01

    Nanomedicine seeks to apply nanoscale materials for the therapy and diagnosis of diseased and damaged tissues. Recent advances in nanotechnology have made a major contribution to the development of multifunctional nanomaterials, which represents a paradigm shift from single purpose to multipurpose materials. Multifunctional nanomaterials have been proposed to enable simultaneous target imaging and on-demand delivery of therapeutic agents only to the specific site. Most advanced systems are also responsive to internal or external stimuli. This approach is particularly important for highly potent drugs (e.g. chemotherapeutics), which should be delivered in a discreet manner and interact with cells/tissues only locally. Both advances in imaging and precisely controlled and localized delivery are critically important in cancer treatment, and the use of such systems - theranostics - holds great promise to minimise side effects and boost therapeutic effectiveness of the treatment. Among others, mesoporous silica nanoparticles (MSNPs) are considered one of the most promising nanomaterials for drug delivery. Due to their unique intrinsic features, including tunable porosity and size, large surface area, structural diversity, easily modifiable chemistry and suitability for functionalization, and biocompatibility, MSNPs have been extensively utilized as multifunctional nanocarrier systems. The combination or hybridization with biomolecules, drugs, and other nanoparticles potentiated the ability of MSNPs towards multifunctionality, and even smart actions stimulated by specified signals, including pH, optical signal, redox reaction, electricity and magnetism. This paper provides a comprehensive review of the state-of-the-art of multifunctional, smart drug delivery systems centered on advanced MSNPs, with special emphasis on cancer related applications.

  5. Silk Fibroin-Based Nanoparticles for Drug Delivery

    Science.gov (United States)

    Zhao, Zheng; Li, Yi; Xie, Mao-Bin

    2015-01-01

    Silk fibroin (SF) is a protein-based biomacromolecule with excellent biocompatibility, biodegradability and low immunogenicity. The development of SF-based nanoparticles for drug delivery have received considerable attention due to high binding capacity for various drugs, controlled drug release properties and mild preparation conditions. By adjusting the particle size, the chemical structure and properties, the modified or recombinant SF-based nanoparticles can be designed to improve the therapeutic efficiency of drugs encapsulated into these nanoparticles. Therefore, they can be used to deliver small molecule drugs (e.g., anti-cancer drugs), protein and growth factor drugs, gene drugs, etc. This paper reviews recent progress on SF-based nanoparticles, including chemical structure, properties, and preparation methods. In addition, the applications of SF-based nanoparticles as carriers for therapeutic drugs are also reviewed. PMID:25749470

  6. Iron Oxide Nanoparticles for Magnetically-Guided and Magnetically-Responsive Drug Delivery

    Directory of Open Access Journals (Sweden)

    Joan Estelrich

    2015-04-01

    Full Text Available In this review, we discuss the recent advances in and problems with the use of magnetically-guided and magnetically-responsive nanoparticles in drug delivery and magnetofection. In magnetically-guided nanoparticles, a constant external magnetic field is used to transport magnetic nanoparticles loaded with drugs to a specific site within the body or to increase the transfection capacity. Magnetofection is the delivery of nucleic acids under the influence of a magnetic field acting on nucleic acid vectors that are associated with magnetic nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles are encapsulated or embedded in a larger colloidal structure that carries a drug. In this last case, an alternating magnetic field can modify the structure of the colloid, thereby providing spatial and temporal control over drug release.

  7. Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems

    Science.gov (United States)

    Mullen, Douglas Gurnett

    Characterization and control of heterogeneous distributions of nanoparticle-ligand components are major design challenges for nanoparticle-based platforms. This dissertation begins with an examination of poly(amidoamine) (PAMAM) dendrimer-based targeted delivery platform. A folic acid targeted modular platform was developed to target human epithelial cancer cells. Although active targeting was observed in vitro, active targeting was not found in vivo using a mouse tumor model. A major flaw of this platform design was that it did not provide for characterization or control of the component distribution. Motivated by the problems experienced with the modular design, the actual composition of nanoparticle-ligand distributions were examined using a model dendrimer-ligand system. High Pressure Liquid Chromatography (HPLC) resolved the distribution of components in samples with mean ligand/dendrimer ratios ranging from 0.4 to 13. A peak fitting analysis enabled the quantification of the component distribution. Quantified distributions were found to be significantly more heterogeneous than commonly expected and standard analytical parameters, namely the mean ligand/nanoparticle ratio, failed to adequately represent the component heterogeneity. The distribution of components was also found to be sensitive to particle modifications that preceded the ligand conjugation. With the knowledge gained from this detailed distribution analysis, a new platform design was developed to provide a system with dramatically improved control over the number of components and with improved batch reproducibility. Using semi-preparative HPLC, individual dendrimer-ligand components were isolated. The isolated dendrimer with precise numbers of ligands were characterized by NMR and analytical HPLC. In total, nine different dendrimer-ligand components were obtained with degrees of purity ≥80%. This system has the potential to serve as a platform to which a precise number of functional molecules

  8. Natural material-decorated mesoporous silica nanoparticle container for multifunctional membrane-controlled targeted drug delivery

    Directory of Open Access Journals (Sweden)

    Hu Y

    2017-11-01

    Full Text Available Yan Hu,1 Lei Ke,2 Hao Chen,1 Ma Zhuo,1 Xinzhou Yang,1 Dan Zhao,1 Suying Zeng,1 Xincai Xiao1 1Department of Pharmaceutics, School of Pharmaceutical Science, South-Central University for Nationalities, 2Department of Medicinal Chemistry, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China Abstract: To avoid the side effects caused by nonspecific targeting, premature release, weak selectivity, and poor therapeutic efficacy of current nanoparticle-based systems used for drug delivery, we fabricated natural material-decorated nanoparticles as a multifunctional, membrane-controlled targeted drug delivery system. The nanocomposite material coated with a membrane was biocompatible and integrated both specific tumor targeting and responsiveness to stimulation, which improved transmission efficacy and controlled drug release. Mesoporous silica nanoparticles (MSNs, which are known for their biocompatibility and high drug-loading capacity, were selected as a model drug container and carrier. The membrane was established by the polyelectrolyte composite method from chitosan (CS which was sensitive to the acidic tumor microenvironment, folic acid-modified CS which recognizes the folate receptor expressed on the tumor cell surface, and a CD44 receptor-targeted polysaccharide hyaluronic acid. We characterized the structure of the nanocomposite as well as the drug release behavior under the control of the pH-sensitive membrane switch and evaluated the antitumor efficacy of the system in vitro. Our results provide a basis for the design and fabrication of novel membrane-controlled nanoparticles with improved tumor-targeting therapy. Keywords: multifunctional, membrane-controlled, natural materials, mesoporous silica nanoparticles, targeted drug delivery

  9. Advanced drug delivery systems: Nanotechnology of health design A review

    Directory of Open Access Journals (Sweden)

    Javad Safari

    2014-04-01

    Full Text Available Nanotechnology has finally and firmly entered the realm of drug delivery. Performances of intelligent drug delivery systems are continuously improved with the purpose to maximize therapeutic activity and to minimize undesirable side-effects. This review describes the advanced drug delivery systems based on micelles, polymeric nanoparticles, and dendrimers. Polymeric carbon nanotubes and many others demonstrate a broad variety of useful properties. This review emphasizes the main requirements for developing new nanotech-nology-based drug delivery systems.

  10. Potential of insulin nanoparticle formulations for oral delivery and diabetes treatment.

    Science.gov (United States)

    Wong, Chun Y; Al-Salami, Hani; Dass, Crispin R

    2017-10-28

    Nanoparticles have demonstrated significant advancements in potential oral delivery of insulin. In this publication, we review the current status of polymeric, inorganic and solid-lipid nanoparticles designed for oral administration of insulin. Firstly, the structure and physiological function of insulin are examined. Then, the efficiency and shortcomings of insulin nanoparticle are discussed. These include the susceptibility to digestive enzyme degradation, instability in the acidic pH environment, poor mucus diffusion and inadequate permeation through the gastrointestinal epithelium. In order to optimise the nanocarriers, the following considerations, including polymer nature, surface charge, size, polydispersity index and morphology of nanoparticles, have to be taken into account. Some novel designs such as chitosan-based glucose-responsive nanoparticles, layer by layer technique-based nanoparticles and zwitterion nanoparticles are being adopted to overcome the physiological challenges. The review ends with some future directions and challenges to be addressed for the success of oral delivery of insulin-loaded nanoparticle formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Nanoparticle for delivery of antisense γPNA oligomers targeting CCR5

    OpenAIRE

    Bahal, Raman; McNeer, Nicole Ali; Ly, Danith H.; Saltzman, W. Mark; Glazer, Peter M.

    2013-01-01

    The development of a new class of peptide nucleic acids (PNAs), i.e., gamma PNAs (γPNAs), creates the need for a general and effective method for its delivery into cells for regulating gene expression in mammalian cells. Here we report the antisense activity of a recently developed hydrophilic and biocompatible diethylene glycol (miniPEG)-based gamma peptide nucleic acid called MPγPNAs via its delivery by poly(lactide-co-glycolide) (PLGA)-based nanoparticle system. We show that MPγPNA oligome...

  12. Physics considerations in targeted anticancer drug delivery by magnetoelectric nanoparticles

    Science.gov (United States)

    Stimphil, Emmanuel; Nagesetti, Abhignyan; Guduru, Rakesh; Stewart, Tiffanie; Rodzinski, Alexandra; Liang, Ping; Khizroev, Sakhrat

    2017-06-01

    In regard to cancer therapy, magnetoelectric nanoparticles (MENs) have proven to be in a class of its own when compared to any other nanoparticle type. Like conventional magnetic nanoparticles, they can be used for externally controlled drug delivery via application of a magnetic field gradient and image-guided delivery. However, unlike conventional nanoparticles, due to the presence of a non-zero magnetoelectric effect, MENs provide a unique mix of important properties to address key challenges in modern cancer therapy: (i) a targeting mechanism driven by a physical force rather than antibody matching, (ii) a high-specificity delivery to enhance the cellular uptake of therapeutic drugs across the cancer cell membranes only, while sparing normal cells, (iii) an externally controlled mechanism to release drugs on demand, and (iv) a capability for image guided precision medicine. These properties separate MEN-based targeted delivery from traditional biotechnology approaches and lay a foundation for the complementary approach of technobiology. The biotechnology approach stems from the underlying biology and exploits bioinformatics to find the right therapy. In contrast, the technobiology approach is geared towards using the physics of molecular-level interactions between cells and nanoparticles to treat cancer at the most fundamental level and thus can be extended to all the cancers. This paper gives an overview of the current state of the art and presents an ab initio model to describe the underlying mechanisms of cancer treatment with MENs from the perspective of basic physics.

  13. Lipid nanoparticles (SLN & NLC) for delivery of vitamin E: a comprehensive review.

    Science.gov (United States)

    Saez, V; Souza, I D L; Mansur, C R E

    2018-04-01

    The antioxidative and photoprotective properties of vitamin E have caused it to be included as an active agent in various pharmaceutical and cosmetic products. However, its lipophilicity, chemical instability and poor skin penetration have limited the effectiveness of these formulations. For that reason, many attempts to include it in different drug delivery systems have been made. In recent decades, lipid nanoparticles have received special attention due to their advantages of compatibility with the skin, ability to enhance penetration of drugs in the stratum corneum, protection of the encapsulated substance against degradation induced by the external medium and control of drug release. This work reviews the current status of the encapsulation of vitamin E in lipid nanoparticles. We describe the most important methods for obtaining and characterizing lipid nanoparticles containing vitamin E (LNP-VE), various techniques for the evaluation of vitamin E's properties after encapsulation, the main in vitro and in vivo studies of the potential effectiveness or toxicity of LNP-VE, the formulations and stability studies of this delivery system, the commercial products based on LNP-VE and the regulatory aspects related to lipid nanoparticles. Finally, we discuss the most relevant advantages of encapsulating vitamin E in such particles and critical aspects that still demand attention to enhance the potential of solid lipid nanoparticles to deliver vitamin E. © 2018 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  14. Challenges in modelling nanoparticles for drug delivery

    International Nuclear Information System (INIS)

    Barnard, Amanda S

    2016-01-01

    Although there have been significant advances in the fields of theoretical condensed matter and computational physics, when confronted with the complexity and diversity of nanoparticles available in conventional laboratories a number of modeling challenges remain. These challenges are generally shared among application domains, but the impacts of the limitations and approximations we make to overcome them (or circumvent them) can be more significant one area than another. In the case of nanoparticles for drug delivery applications some immediate challenges include the incompatibility of length-scales, our ability to model weak interactions and solvation, the complexity of the thermochemical environment surrounding the nanoparticles, and the role of polydispersivity in determining properties and performance. Some of these challenges can be met with existing technologies, others with emerging technologies including the data-driven sciences; some others require new methods to be developed. In this article we will briefly review some simple methods and techniques that can be applied to these (and other) challenges, and demonstrate some results using nanodiamond-based drug delivery platforms as an exemplar. (topical review)

  15. Current understanding of interactions between nanoparticles and the immune system.

    Science.gov (United States)

    Dobrovolskaia, Marina A; Shurin, Michael; Shvedova, Anna A

    2016-05-15

    The delivery of drugs, antigens, and imaging agents benefits from using nanotechnology-based carriers. The successful translation of nanoformulations to the clinic involves thorough assessment of their safety profiles, which, among other end-points, includes evaluation of immunotoxicity. The past decade of research focusing on nanoparticle interaction with the immune system has been fruitful in terms of understanding the basics of nanoparticle immunocompatibility, developing a bioanalytical infrastructure to screen for nanoparticle-mediated immune reactions, beginning to uncover the mechanisms of nanoparticle immunotoxicity, and utilizing current knowledge about the structure-activity relationship between nanoparticles' physicochemical properties and their effects on the immune system to guide safe drug delivery. In the present review, we focus on the most prominent pieces of the nanoparticle-immune system puzzle and discuss the achievements, disappointments, and lessons learned over the past 15years of research on the immunotoxicity of engineered nanomaterials. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Systemic delivery of blood-brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue.

    Science.gov (United States)

    Saucier-Sawyer, Jennifer K; Deng, Yang; Seo, Young-Eun; Cheng, Christopher J; Zhang, Junwei; Quijano, Elias; Saltzman, W Mark

    2015-01-01

    Delivery of therapeutic agents to the central nervous system is a significant challenge, hindering progress in the treatment of diseases such as glioblastoma. Due to the presence of the blood-brain barrier (BBB), therapeutic agents do not readily transverse the brain endothelium to enter the parenchyma. Previous reports suggest that surface modification of polymer nanoparticles (NPs) can improve their ability to cross the BBB, but it is unclear whether the observed enhancements in transport are large enough to enhance therapy. In this study, we synthesized two degradable polymer NP systems surface-modified with ligands previously suggested to improve BBB transport, and tested their ability to cross the BBB after intravenous injection in mice. All the NP preparations were able to cross the BBB, although generally in low amounts (brain uptake (∼0.8% of the injected dose): a block copolymer of polylactic acid and hyperbranched polyglycerol, surface modified with adenosine (PLA-HPG-Ad). PLA-HPG-Ad NPs provided controlled release of camptothecin, killing U87 glioma cells in culture. When administered intravenously in mice with intracranial U87 tumors, they failed to increase survival. These results suggest that enhancing NP transport across the BBB does not necessarily yield proportional pharmacological effects.

  17. Current understanding of interactions between nanoparticles and the immune system

    International Nuclear Information System (INIS)

    Dobrovolskaia, Marina A.; Shurin, Michael; Shvedova, Anna A.

    2016-01-01

    The delivery of drugs, antigens, and imaging agents benefits from using nanotechnology-based carriers. The successful translation of nanoformulations to the clinic involves thorough assessment of their safety profiles, which, among other end-points, includes evaluation of immunotoxicity. The past decade of research focusing on nanoparticle interaction with the immune system has been fruitful in terms of understanding the basics of nanoparticle immunocompatibility, developing a bioanalytical infrastructure to screen for nanoparticle-mediated immune reactions, beginning to uncover the mechanisms of nanoparticle immunotoxicity, and utilizing current knowledge about the structure–activity relationship between nanoparticles' physicochemical properties and their effects on the immune system to guide safe drug delivery. In the present review, we focus on the most prominent pieces of the nanoparticle–immune system puzzle and discuss the achievements, disappointments, and lessons learned over the past 15 years of research on the immunotoxicity of engineered nanomaterials. - Graphical abstract: API — active pharmaceutical ingredient; NP — nanoparticles; PCP — physicochemical properties, CARPA — complement activation-related pseudoallergy, ICH — International Conference on Harmonization. Display Omitted - Highlights: • Achievements, disappointments and lessons learned over past decade are reviewed. • Areas in focus include characterization, immunotoxicity and utility in drug delivery. • Future direction focusing on mechanistic immunotoxicity studies is proposed.

  18. Current understanding of interactions between nanoparticles and the immune system

    Energy Technology Data Exchange (ETDEWEB)

    Dobrovolskaia, Marina A., E-mail: marina@mail.nih.gov [Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, NCI at Frederick, Frederick, MD 21702 (United States); Shurin, Michael [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Department of Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Shvedova, Anna A., E-mail: ats1@cdc.gov [Health Effects Laboratory Division, National Institute of Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505 (United States); Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV 26506 (United States)

    2016-05-15

    The delivery of drugs, antigens, and imaging agents benefits from using nanotechnology-based carriers. The successful translation of nanoformulations to the clinic involves thorough assessment of their safety profiles, which, among other end-points, includes evaluation of immunotoxicity. The past decade of research focusing on nanoparticle interaction with the immune system has been fruitful in terms of understanding the basics of nanoparticle immunocompatibility, developing a bioanalytical infrastructure to screen for nanoparticle-mediated immune reactions, beginning to uncover the mechanisms of nanoparticle immunotoxicity, and utilizing current knowledge about the structure–activity relationship between nanoparticles' physicochemical properties and their effects on the immune system to guide safe drug delivery. In the present review, we focus on the most prominent pieces of the nanoparticle–immune system puzzle and discuss the achievements, disappointments, and lessons learned over the past 15 years of research on the immunotoxicity of engineered nanomaterials. - Graphical abstract: API — active pharmaceutical ingredient; NP — nanoparticles; PCP — physicochemical properties, CARPA — complement activation-related pseudoallergy, ICH — International Conference on Harmonization. Display Omitted - Highlights: • Achievements, disappointments and lessons learned over past decade are reviewed. • Areas in focus include characterization, immunotoxicity and utility in drug delivery. • Future direction focusing on mechanistic immunotoxicity studies is proposed.

  19. A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system

    Directory of Open Access Journals (Sweden)

    Wang S

    2018-01-01

    Full Text Available Shaowei Wang,1 Xiaochun Wei,1 Xiaojuan Sun,1 Chongwei Chen,1 Jingming Zhou,2 Ge Zhang,3 Heng Wu,3 Baosheng Guo,3 Lei Wei1,2 1Department of Orthopaedics, The 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi, China; 2Department of Orthopaedics, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA; 3Integrated Traditional Chinese and Western Medicine, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Background: Cartilage degeneration affects millions of people but preventing its degeneration is a big challenge. Although RNA interference (RNAi has been used in human trials via silencing specific genes, the cartilage RNAi has not been possible to date because the cartilage is an avascular and very dense tissue with very low permeability. Purpose: The objective of this study was to develop and validate a novel lipid nanoparticle (LNP-siRNA delivery system that can prevent cartilage degeneration by knocking down specific genes. Methods: LNP transfection efficiency was evaluated in vitro and ex vivo. Indian Hedgehog (Ihh has been correlated with cartilage degeneration. The in vivo effects of LNP-Ihh siRNA complexes on cartilage degeneration were evaluated in a rat model of surgery-induced osteoarthritis (OA. Results: In vitro, 100% of chondrocytes were transfected with siRNA in the LNP-siRNA group. In accordance with the cell culture results, red positive signals could be detected even in the deep layer of cartilage tissue cultures treated by LNP-beacon. In vivo data showed that LNP is specific for cartilage, since positive signals were detected by fluorescence molecular tomography and confocal microscopy in joint cartilage injected with LNP-beacon, but not on the surface of the synovium. In the rat model of OA, intraarticular injection of LNP-Ihh siRNA attenuated OA progression, and PCR results showed LNP-Ihh siRNA exerted a positive impact on anabolic metabolism and negative

  20. Cyclodextrin-insulin complex encapsulated polymethacrylic acid based nanoparticles for oral insulin delivery.

    Science.gov (United States)

    Sajeesh, S; Sharma, Chandra P

    2006-11-15

    Present investigation was aimed at developing an oral insulin delivery system based on hydroxypropyl beta cyclodextrin-insulin (HPbetaCD-I) complex encapsulated polymethacrylic acid-chitosan-polyether (polyethylene glycol-polypropylene glycol copolymer) (PMCP) nanoparticles. Nanoparticles were prepared by the free radical polymerization of methacrylic acid in presence of chitosan and polyether in a solvent/surfactant free medium. Dynamic light scattering (DLS) experiment was conducted with particles dispersed in phosphate buffer (pH 7.4) and size distribution curve was observed in the range of 500-800 nm. HPbetaCD was used to prepare non-covalent inclusion complex with insulin and complex was analyzed by Fourier transform infrared (FTIR) and fluorescence spectroscopic studies. HPbetaCD complexed insulin was encapsulated into PMCP nanoparticles by diffusion filling method and their in vitro release profile was evaluated at acidic/alkaline pH. PMCP nanoparticles displayed good insulin encapsulation efficiency and release profile was largely dependent on the pH of the medium. Enzyme linked immunosorbent assay (ELISA) study demonstrated that insulin encapsulated inside the particles was biologically active. Trypsin inhibitory effect of PMCP nanoparticles was evaluated using N-alpha-benzoyl-L-arginine ethyl ester (BAEE) and casein as substrates. Mucoadhesive studies of PMCP nanoparticles were conducted using freshly excised rat intestinal mucosa and the particles were found fairly adhesive. From the preliminary studies, cyclodextrin complexed insulin encapsulated mucoadhesive nanoparticles appear to be a good candidate for oral insulin delivery.

  1. Magnetic control of potential microrobotic drug delivery systems: nanoparticles, magnetotactic bacteria and self-propelled microjets.

    Science.gov (United States)

    Khalil, Islam S M; Magdanz, Veronika; Sanchez, Samuel; Schmidt, Oliver G; Abelmann, Leon; Misra, Sarthak

    2013-01-01

    Development of targeted drug delivery systems using magnetic microrobots increases the therapeutic indices of drugs. These systems have to be incorporated with precise motion controllers. We demonstrate closed-loop motion control of microrobots under the influence of controlled magnetic fields. Point-to-point motion control of a cluster of iron oxide nanoparticles (diameter of 250 nm) is achieved by pulling the cluster towards a reference position using magnetic field gradients. Magnetotactic bacterium (MTB) is controlled by orienting the magnetic fields towards a reference position. MTB with membrane length of 5 µm moves towards the reference position using the propulsion force generated by its flagella. Similarly, self-propelled microjet with length of 50 µm is controlled by directing the microjet towards a reference position by external magnetic torque. The microjet moves along the field lines using the thrust force generated by the ejecting oxygen bubbles from one of its ends. Our control system positions the cluster of nanoparticles, an MTB and a microjet at an average velocity of 190 µm/s, 28 µm/s, 90 µm/s and within an average region-of-convergence of 132 µm, 40 µm, 235 µm, respectively.

  2. Nanoparticle-Based Drug Delivery for Therapy of Lung Cancer: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Anish Babu

    2013-01-01

    Full Text Available The last decade has witnessed enormous advances in the development and application of nanotechnology in cancer detection, diagnosis, and therapy culminating in the development of the nascent field of “cancer nanomedicine.” A nanoparticle as per the National Institutes of Health (NIH guidelines is any material that is used in the formulation of a drug resulting in a final product smaller than 1 micron in size. Nanoparticle-based therapeutic systems have gained immense popularity due to their ability to overcome biological barriers, effectively deliver hydrophobic therapies, and preferentially target disease sites. Currently, many formulations of nanocarriers are utilized including lipid-based, polymeric and branched polymeric, metal-based, magnetic, and mesoporous silica. Innovative strategies have been employed to exploit the multicomponent, three-dimensional constructs imparting multifunctional capabilities. Engineering such designs allows simultaneous drug delivery of chemotherapeutics and anticancer gene therapies to site-specific targets. In lung cancer, nanoparticle-based therapeutics is paving the way in the diagnosis, imaging, screening, and treatment of primary and metastatic tumors. However, translating such advances from the bench to the bedside has been severely hampered by challenges encountered in the areas of pharmacology, toxicology, immunology, large-scale manufacturing, and regulatory issues. This review summarizes current progress and challenges in nanoparticle-based drug delivery systems, citing recent examples targeted at lung cancer treatment.

  3. PLGA-Chitosan nanoparticle-mediated gene delivery for oral cancer treatment: A brief review

    Science.gov (United States)

    Bakar, L. M.; Abdullah, M. Z.; Doolaanea, A. A.; Ichwan, S. J. A.

    2017-08-01

    Cancer becomes a serious issue on society with increasing of their growth and proliferation, either in well economic developed countries or not. Recent years, oral cancer is one of the most threatening diseases impairing the quality of life of the patient. Scientists have emphasised on application of gene therapy for oral cancer by using nanoparticle as transportation vectors as a new alternative platform in order to overcome the limitations of conventional approaches. In modern medicine, nanotechnologies’ application, such as nanoparticles-mediated gene delivery, is one of promising tool for therapeutic devices. The objective of this article is to present a brief review summarizes on the current progress of nanotechnology-based gene delivery treatment system targeted for oral cancer.

  4. Polymeric nanoparticles for the intracellular delivery of paclitaxel in lung and breast cancer

    Science.gov (United States)

    Zubris, Kimberly Ann Veronica

    Nanoparticles are useful for addressing many of the difficulties encountered when administering therapeutic compounds. Nanoparticles are able to increase the solubility of hydrophobic drugs, improve pharmacokinetics through sustained release, alter biodistribution, protect sensitive drugs from low pH environments or enzymatic alteration, and, in some cases, provide targeting of the drug to the desired tissues. The use of functional nanocarriers can also provide controlled intracellular delivery of a drug. To this end, we have developed functional pH-responsive expansile nanoparticles for the intracellular delivery of paclitaxel. The pH-responsiveness of these nanoparticles occurs due to a hydrophobic to hydrophilic transition of the polymer occurring under mildly acidic conditions. These polymeric nanoparticles were systematically evaluated for the delivery of paclitaxel in vitro and in vivo to improve local therapy for lung and breast cancers. Nanoparticles were synthesized using a miniemulsion polymerization process and were subsequently characterized and found to swell when exposed to acidic environments. Paclitaxel was successfully encapsulated within the nanoparticles, and the particles exhibited drug release at pH 5 but not at pH 7.4. In addition, the uptake of nanoparticles was observed using flow cytometry, and the anticancer efficacy of the paclitaxel-loaded nanoparticles was measured using cancer cell lines in vitro. The potency of the paclitaxel-loaded nanoparticles was close to that of free drug, demonstrating that the drug was effectively delivered by the particles and that the particles could act as an intracellular drug depot. Following in vitro characterization, murine in vivo studies demonstrated the ability of the paclitaxel-loaded responsive nanoparticles to delay recurrence of lung cancer and to prevent establishment of breast cancer in the mammary fat pads with higher efficacy than paclitaxel alone. In addition, the ability of nanoparticles to

  5. Nanoparticles as conjugated delivery agents for therapeutic applications

    Science.gov (United States)

    Muroski, Megan Elizabeth

    This dissertation explores the use of nanoparticles as conjugated delivery agents. Chapter 1 is a general introduction. Chapter 2 discusses the delivery by a nanoparticle platform provides a method to manipulate gene activation, by taking advantage of the high surface area of a nanoparticle and the ability to selectively couple a desired biological moiety to the NP surface. The nanoparticle based transfection approach functions by controlled release of gene regulatory elements from a 6 nm AuNP (gold nanoparticle) surface. The endosomal release of the regulatory elements from the nanoparticle surface results in endogenous protein knockdown simultaneously with exogenous protein expression for the first 48 h. The use of fluorescent proteins as the endogenous and exogenous signals for protein expression enables the efficiency of co-delivery of siRNA (small interfering RNA) for GFP (green fluorescent protein) knockdown and a dsRed-express linearized plasmid for induction to be optically analyzed in CRL-2794, a human kidney cell line expressing an unstable green fluorescent protein. Delivery of the bimodal nanoparticle in cationic liposomes results in 20% GFP knockdown within 24 h of delivery and continues exhibiting knockdown for up to 48 h for the bimodal agent. Simultaneous dsRed expression is observed to initiate within the same time frame with expression levels reaching 34% after 25 days although cells have divided approximately 20 times, implying daughter cell transfection has occurred. Fluorescence cell sorting results in a stable colony, as demonstrated by Western blot analysis. The simultaneous delivery of siRNA and linearized plasmid DNA on the surface of a single nanocrystal provides a unique method for definitive genetic control within a single cell and leads to a very efficient cell transfection protocol. In Chapter 3, we wanted to understand the NP complex within the cell, and to look at the dynamics of release utilizing nanometal surface energy transfer as

  6. Nanotechnology-based drug delivery systems

    Directory of Open Access Journals (Sweden)

    Singh Baljit

    2007-12-01

    Full Text Available Abstract Nanoparticles hold tremendous potential as an effective drug delivery system. In this review we discussed recent developments in nanotechnology for drug delivery. To overcome the problems of gene and drug delivery, nanotechnology has gained interest in recent years. Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. To achieve efficient drug delivery it is important to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signalling involved in pathobiology of the disease under consideration. Several anti-cancer drugs including paclitaxel, doxorubicin, 5-fluorouracil and dexamethasone have been successfully formulated using nanomaterials. Quantom dots, chitosan, Polylactic/glycolic acid (PLGA and PLGA-based nanoparticles have also been used for in vitro RNAi delivery. Brain cancer is one of the most difficult malignancies to detect and treat mainly because of the difficulty in getting imaging and therapeutic agents past the blood-brain barrier and into the brain. Anti-cancer drugs such as loperamide and doxorubicin bound to nanomaterials have been shown to cross the intact blood-brain barrier and released at therapeutic concentrations in the brain. The use of nanomaterials including peptide-based nanotubes to target the vascular endothelial growth factor (VEGF receptor and cell adhesion molecules like integrins, cadherins and selectins, is a new approach to control disease progression.

  7. PLGA nanoparticles as chlorhexidine-delivery carrier to resin-dentin adhesive interface.

    Science.gov (United States)

    Priyadarshini, Balasankar Meera; Mitali, Kakran; Lu, Thong Beng; Handral, Harish K; Dubey, Nileshkumar; Fawzy, Amr S

    2017-07-01

    To characterize and deliver fabricated CHX-loaded PLGA-nanoparticles inside micron-sized dentinal-tubules of demineralized dentin-substrates and resin-dentin interface. Nanoparticles fabricated by emulsion evaporation were assessed in-vitro by different techniques. Delivery of drug-loaded nanoparticles to demineralized dentin substrates, interaction with collagen matrix, and ex-vivo CHX-release profiles using extracted teeth connected to experimental setup simulating pulpal hydrostatic pressure were investigated. Furthermore, nanoparticles association/interaction with a commercial dentin-adhesive applied to demineralized dentin substrates were examined. The results showed that the formulated nanoparticles demonstrated attractive physicochemical properties, low cytotoxicity, potent antibacterial efficacy, and slow degradation and gradual CHX release profiles. Nanoparticles delivered efficiently inside dentinal-tubules structure to sufficient depth (>10μm) against the simulated upward pulpal hydrostatic-pressure, even after bonding-resins infiltration and were attached/retained on collagen-fibrils. These results verified the potential significance of this newly introduced drug-delivery therapeutic strategy for future clinical applications and promote for a new era of future dental research. This innovative drug-delivery strategy has proven to be a reliable method for delivering treatments that could be elaborated for other clinical applications in adhesive and restorative dentistry. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  8. Nanoparticle synthesis and delivery by an aerosol route for watermelon plant foliar uptake

    Science.gov (United States)

    Wang, Wei-Ning; Tarafdar, Jagadish C.; Biswas, Pratim

    2013-01-01

    An aerosol process was developed for synthesis and delivery of nanoparticles for living watermelon plant foliar uptake. This is an efficient technique capable of generating nanoparticles with controllable particle sizes and number concentrations. Aerosolized nanoparticles were easily applied to leaf surfaces and enter the stomata via gas uptake, avoiding direct interaction with soil systems, eliminating potential ecological risks. The uptake and transport of nanoparticles inside the watermelon plants were investigated systematically by various techniques, such as elemental analysis by inductively coupled plasma mass spectrometry and plant anatomy by transmission electron microscopy. The results revealed that certain fractions of nanoparticles ( d p watermelon plants. The particle size and number concentration played an important role in nanoparticle translocation inside the plants. In addition, the nanoparticle application method, working environment, and leaf structure are also important factors to be considered for successful plant foliar uptake.

  9. Development of Cy5.5-Labeled Hydrophobically Modified Glycol Chitosan Nanoparticles for Protein Delivery

    Science.gov (United States)

    Chin, Amanda

    Therapeutic proteins are often highly susceptible to enzymatic degradation, thus restricting their in vivo stability. To overcome this limitation, delivery systems designed to promote uptake and reduce degradation kinetics have undergone a rapid shift from macro-scale systems to nanomaterial based carriers. Many of these nanomaterials, however, elicit immune responses and may have cytotoxic effects both in vitro and in vivo. The naturally derived polysaccharide chitosan has emerged as a promising biodegradable material and has been utilized for many biomedical applications; nevertheless, its function is often constrained by poor solubility. Glycol chitosan, a derivative of chitosan, can be hydrophobically modified to impart amphiphilic properties that enable the self-assembly into nanoparticles in aqueous media at neutral pH. This nanoparticle system has shown initial success as a therapeutic agent in several model cell culture systems, but little is known about its stability against enzymatic degradation. Therefore, the goal of this research was to investigate the resistance of hydrophobically modified glycol chitosan against enzyme-catalyzed degradation using an in vivo simulated system containing lysozyme. To synthesize the nanoparticles, hydrophobic cholanic acid was first covalently conjugated to glycol chitosan using of N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Conjugates were purified by dialysis, lyophilized, and ultra-sonicated to form nanoparticles. Fourier transform infrared (FT-IR) spectroscopy confirmed the binding of 5beta-cholanic acid to the glycol chitosan. Particle size and stability over time were determined with dynamic light scattering (DLS), and particle morphology was evaluated by transmission electron microscopy (TEM). The average diameter of the nanoparticles was approximately 200 nm, which remained stable at 4°C for up to 10 days. Additionally, a near infrared fluorescent (NIRF) dye

  10. Design and Synthesis of Self-Assembled Polymeric Nanoparticles for Cancer Drug Delivery

    Science.gov (United States)

    Logie, Jennifer

    Current chemotherapeutics are plagued by poor solubility and selectivity, requiring toxic excipients in formulations and causing a number of dose limiting side effects. Nanoparticle delivery has emerged as a strategy to more effectively deliver chemotherapeutics to the tumour site. Specifically, polymeric micelles enable the solubilization of hydrophobic small molecule drugs within the core and mitigate the necessity of excipients. Notwithstanding the significant progress made in polymeric micelle delivery, translation is limited by poor stability and low drug loading. In this work, a rational design approach is used to chemically modify poly(D,L-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (P(LA-co-TMCC)-g-PEG) in order to overcome these limitations and effectively deliver drug to tumours. The PEG density of the polymer system was optimized to enhance the stability of our polymeric micelles. Higher PEG densities permitted the lyophilization of micelles and enhanced the serum stability of the system. To increase the drug loading of our system, we facilitated specific intermolecular interactions within the micelle core. For drugs that form colloidal aggregates, such as pentyl-PABC doxazolidine, polymers were used to stabilize the colloidal core against aggregation and protein adsorption. For more challenging molecules, where self-assembly cannot be controlled, such as docetaxel, we modified the polymeric backbone with a peptide from the binding site of the drug to achieve loadings five times higher than those achieved in conventional micelle systems. This novel docetaxel nanoparticle was assessed in vivo in an orthotopic mouse model of breast cancer, where it showed a wider therapeutic index than the conventional ethanolic polysorbate 80 formulation. The improved tolerability of this formulation enabled higher dosing regimens and led to heightened efficacy and survival in this mouse model. Combined, these studies validated P

  11. Long-circulating Janus nanoparticles made by electrohydrodynamic co-jetting for systemic drug delivery applications

    Science.gov (United States)

    Rahmani, Sahar; Villa, Carlos H.; Dishman, Acacia F.; Grabowski, Marika E.; Pan, Daniel C.; Durmaz, Hakan; Misra, Asish C; Colón-Meléndez, Laura; Solomon, Michael J.; Muzykantov, Vladimir R.; Lahann, Joerg

    2016-01-01

    Background Nanoparticles with controlled physical properties have been widely used for controlled release applications. In addition to shape, the anisotropic nature of the particles can be an important design criterion to ensure selective surface modification or independent release of combinations of drugs. Purpose Electrohydrodynamic (EHD) co-jetting is used for the fabrication of uniform anisotropic nanoparticles with individual compartments and initial physicochemical and biological characterization is reported. Methods EHD co-jetting is used to create nanoparticles, which are characterized at each stage with scanning electron microscopy (SEM), structured illumination microscopy (SIM), dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Surface immobilization techniques are used to incorporate polyethylene glycol (PEG) and I125 radiolabels into the nanoparticles. Particles are injected in mice and the particle distribution after 1, 4 and 24 hours is assessed. Results and discussion Nanoparticles with an average diameter of 105.7 nm are prepared by EHD co-jetting. The particles contain functional chemical groups for further surface modification and radiolabeling. The density of PEG molecules attached to the surface of nanoparticles is determined to range between 0.02 and 6.04 ligands per square nanometer. A significant fraction of the nanoparticles (1.2% injected dose per mass of organ) circulates in the blood after 24 h. Conclusion EHD co-jetting is a versatile method for the fabrication of nanoparticles for drug delivery. Circulation of the nanoparticles for 24 h is a pre-requisite for subsequent studies to explore defined targeting of the nanoparticles to a specific anatomic site. PMID:26453170

  12. Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review.

    Science.gov (United States)

    Calixto, Giovana Maria Fioramonti; Bernegossi, Jéssica; de Freitas, Laura Marise; Fontana, Carla Raquel; Chorilli, Marlus

    2016-03-11

    Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs) with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), gold nanoparticles (AuNPs), hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

  13. Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review

    Directory of Open Access Journals (Sweden)

    Giovana Maria Fioramonti Calixto

    2016-03-01

    Full Text Available Photodynamic therapy (PDT is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs, solid lipid nanoparticles (SLNs, nanostructured lipid carriers (NLCs, gold nanoparticles (AuNPs, hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

  14. The novel albumin-chitosan core-shell nanoparticles for gene delivery: preparation, optimization and cell uptake investigation

    Energy Technology Data Exchange (ETDEWEB)

    Karimi, Mahdi [Tarbiat Modares University, Department of Nanobiotechnology, Faculty of Biological Sciences (Iran, Islamic Republic of); Avci, Pinar [Massachusetts General Hospital, Wellman Center for Photomedicine (United States); Mobasseri, Rezvan [Tarbiat Modares University, Department of Nanobiotechnology, Faculty of Biological Sciences (Iran, Islamic Republic of); Hamblin, Michael R. [Massachusetts General Hospital, Wellman Center for Photomedicine (United States); Naderi-Manesh, Hossein, E-mail: naderman@modares.ac.ir [Tarbiat Modares University, Department of Nanobiotechnology, Faculty of Biological Sciences (Iran, Islamic Republic of)

    2013-05-15

    Natural polymers and proteins such as chitosan (CS) and albumin (Alb) have recently attracted much attention both in drug delivery and gene delivery. The underlying rationale is their unique properties such as biodegradability, biocompatibility and controlled release. This study aimed to prepare novel albumin-chitosan-DNA (Alb-CS-DNA) core-shell nanoparticles as a plasmid delivery system and find the best conditions for their preparation. Phase separation method and ionic interaction were used for preparation of Alb nanoparticles and Alb-CS-DNA core-shell nanoparticles, respectively. The effects of three important independent variables (1) CS/Alb mass ratio, (2) the ratios of moles of the amine groups of cationic polymers to those of the phosphate groups of DNA (N/P ratio), and (3) Alb concentration, on the nanoparticle size and loading efficiency of the plasmid were investigated and optimized through Box-Behnken design of response surface methodology (RSM). The optimum conditions were found to be CS/Alb mass ratio = 3, N/P ratio = 8.24 and Alb concentration = 0.1 mg/mL. The most critical factors for the size of nanoparticles and loading efficiency were Alb concentration and N/P ratio. The optimized nanoparticles had an average size of 176 {+-} 3.4 nm and loading efficiency of 80 {+-} 3.9 %. Cytotoxicity experiments demonstrated that the prepared nanoparticles were not toxic. The high cellular uptake of nanoparticles ({approx}85 %) was shown by flow cytometry and fluorescent microscopy.

  15. Nanoparticle bioconjugate for controlled cellular delivery of doxorubicin

    Science.gov (United States)

    Sangtani, Ajmeeta; Petryayeva, Eleonora; Wu, Miao; Susumu, Kimihiro; Oh, Eunkeu; Huston, Alan L.; Lasarte-Aragones, Guillermo; Medintz, Igor L.; Algar, W. Russ; Delehanty, James B.

    2018-02-01

    Nanoparticle (NP)-mediated drug delivery offers the potential to overcome limitations of systemic delivery, including the ability to specifically target cargo and control release of NP-associated drug cargo. Doxorubicin (DOX) is a widely used FDA-approved cancer therapeutic; however, multiple side effects limit its utility. Thus, there is wide interest in modulating toxicity after cell delivery. Our goal here was to realize a NP-based DOX-delivery system that can modulate drug toxicity by controlling the release kinetics of DOX from the surface of a hard NP carrier. To achieve this, we employed a quantum dot (QD) as a central scaffold which DOX was appended via three different peptidyl linkages (ester, disulfide, hydrazone) that are cleavable in response to various intracellular conditions. Attachment of a cell penetrating peptide (CPP) containing a positively charged polyarginine sequence facilitates endocytosis of the ensemble. Polyhistidine-driven metal affinity coordination was used to self-assemble both peptides to the QD surface, allowing for fine control over both the ratio of peptides attached to the QD as well as DOX dose delivered to cells. Microplate-based Förster resonance energy transfer assays confirmed the successful ratiometric assembly of the conjugates and functionality of the linkages. Cell delivery experiments and cytotoxicity assays were performed to compare the various cleavable linkages to a control peptide where DOX is attached through an amide bond. The role played by various attachment chemistries used in QD-peptide-drug assemblies and their implications for the rationale in design of NPbased constructs for drug delivery is described here.

  16. Development of a dose-controlled multiculture cell exposure chamber for efficient delivery of airborne and engineered nanoparticles

    International Nuclear Information System (INIS)

    Asimakopoulou, Akrivi; Daskalos, Emmanouil; Papaioannou, Eleni; Konstandopoulos, Athanasios G; Lewinski, Nastassja; Riediker, Michael

    2013-01-01

    In order to study the various health influencing parameters related to engineered nanoparticles as well as to soot emitted by Diesel engines, there is an urgent need for appropriate sampling devices and methods for cell exposure studies that simulate the respiratory system and facilitate associated biological and toxicological tests. The objective of the present work was the further advancement of a Multiculture Exposure Chamber (MEC) into a dose-controlled system for efficient delivery of nanoparticles to cells. It was validated with various types of nanoparticles (Diesel engine soot aggregates, engineered nanoparticles for various applications) and with state-of-the-art nanoparticle measurement instrumentation to assess the local deposition of nanoparticles on the cell cultures. The dose of nanoparticles to which cell cultures are being exposed was evaluated in the normal operation of the in vitro cell culture exposure chamber based on measurements of the size specific nanoparticle collection efficiency of a cell free device. The average efficiency in delivering nanoparticles in the MEC was approximately 82%. The nanoparticle deposition was demonstrated by Transmission Electron Microscopy (TEM). Analysis and design of the MEC employs Computational Fluid Dynamics (CFD) and true to geometry representations of nanoparticles with the aim to assess the uniformity of nanoparticle deposition among the culture wells. Final testing of the dose-controlled cell exposure system was performed by exposing A549 lung cell cultures to fluorescently labeled nanoparticles. Delivery of aerosolized nanoparticles was demonstrated by visualization of the nanoparticle fluorescence in the cell cultures following exposure. Also monitored was the potential of the aerosolized nanoparticles to generate reactive oxygen species (ROS) (e.g. free radicals and peroxides generation), thus expressing the oxidative stress of the cells which can cause extensive cellular damage or damage on DNA.

  17. Development of a dose-controlled multiculture cell exposure chamber for efficient delivery of airborne and engineered nanoparticles

    Science.gov (United States)

    Asimakopoulou, Akrivi; Daskalos, Emmanouil; Lewinski, Nastassja; Riediker, Michael; Papaioannou, Eleni; Konstandopoulos, Athanasios G.

    2013-04-01

    In order to study the various health influencing parameters related to engineered nanoparticles as well as to soot emitted by Diesel engines, there is an urgent need for appropriate sampling devices and methods for cell exposure studies that simulate the respiratory system and facilitate associated biological and toxicological tests. The objective of the present work was the further advancement of a Multiculture Exposure Chamber (MEC) into a dose-controlled system for efficient delivery of nanoparticles to cells. It was validated with various types of nanoparticles (Diesel engine soot aggregates, engineered nanoparticles for various applications) and with state-of-the-art nanoparticle measurement instrumentation to assess the local deposition of nanoparticles on the cell cultures. The dose of nanoparticles to which cell cultures are being exposed was evaluated in the normal operation of the in vitro cell culture exposure chamber based on measurements of the size specific nanoparticle collection efficiency of a cell free device. The average efficiency in delivering nanoparticles in the MEC was approximately 82%. The nanoparticle deposition was demonstrated by Transmission Electron Microscopy (TEM). Analysis and design of the MEC employs Computational Fluid Dynamics (CFD) and true to geometry representations of nanoparticles with the aim to assess the uniformity of nanoparticle deposition among the culture wells. Final testing of the dose-controlled cell exposure system was performed by exposing A549 lung cell cultures to fluorescently labeled nanoparticles. Delivery of aerosolized nanoparticles was demonstrated by visualization of the nanoparticle fluorescence in the cell cultures following exposure. Also monitored was the potential of the aerosolized nanoparticles to generate reactive oxygen species (ROS) (e.g. free radicals and peroxides generation), thus expressing the oxidative stress of the cells which can cause extensive cellular damage or damage on DNA.

  18. Electrosprayed nanoparticle delivery system for controlled release

    Energy Technology Data Exchange (ETDEWEB)

    Eltayeb, Megdi, E-mail: megdi.eltayeb@sustech.edu [Department of Biomedical Engineering, Sudan University of Science and Technology, PO Box 407, Khartoum (Sudan); Stride, Eleanor, E-mail: eleanor.stride@eng.ox.ac.uk [Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Old Road Campus Research Building, Headington OX3 7DQ (United Kingdom); Edirisinghe, Mohan, E-mail: m.edirisinghe@ucl.ac.uk [Department of Mechanical Engineering, University College London, Torrington Place, London WC1E 7JE (United Kingdom); Harker, Anthony, E-mail: a.harker@ucl.ac.uk [London Centre for Nanotechnology, Gordon Street, London WC1H 0AH (United Kingdom); Department of Physics & Astronomy, University College London, Gower Street, London WC1E 6BT (United Kingdom)

    2016-09-01

    This study utilises an electrohydrodynamic technique to prepare core-shell lipid nanoparticles with a tunable size and high active ingredient loading capacity, encapsulation efficiency and controlled release. Using stearic acid and ethylvanillin as model shell and active ingredients respectively, we identify the processing conditions and ratios of lipid:ethylvanillin required to form nanoparticles. Nanoparticles with a mean size ranging from 60 to 70 nm at the rate of 1.37 × 10{sup 9} nanoparticles per minute were prepared with different lipid:ethylvanillin ratios. The polydispersity index was ≈ 21% and the encapsulation efficiency ≈ 70%. It was found that the rate of ethylvanillin release was a function of the nanoparticle size, and lipid:ethylvanillin ratio. The internal structure of the lipid nanoparticles was studied by transmission electron microscopy which confirmed that the ethylvanillin was encapsulated within a stearic acid shell. Fourier transform infrared spectroscopy analysis indicated that the ethylvanillin had not been affected. Extensive analysis of the release of ethylvanillin was performed using several existing models and a new diffusive release model incorporating a tanh function. The results were consistent with a core-shell structure. - Highlights: • Electrohydrodynamic spraying is used to produce lipid-coated nanoparticles. • A new model is proposed for the release rates of active components from nanoparticles. • The technique has potential applications in food science and medicine. • Electrohydrodynamic processing controlled release lipid nanoparticles.

  19. A dual-targeting strategy for enhanced drug delivery and synergistic therapy based on thermosensitive nanoparticles.

    Science.gov (United States)

    Wang, Mingxin; You, Chaoqun; Gao, Zhiguo; Wu, Hongshuai; Sun, Baiwang; Zhu, Xiaoli; Chen, Renjie

    2018-08-01

    The functionalized nanoparticles have been widely studied and reported as carriers of drug transport recently. Furthermore, many groups have focused more on developing novel and efficient treatment methods, such as photodynamic therapy and photothermal therapy, since both therapies have shown inspiring potential in the application of antitumor. The mentioned treatments exhibited the superiority of cooperative manner and showed the ability to compensate for the adverse effects caused by conventional monotherapy in proposed strategies. In view of the above descriptions, we formulated a thermosensitive drug delivery system, which achieved the enhanced delivery of cisplatin and two photosensitizers (ICG and Ce6) by dual-targeting traction. Drawing on the thin film hydration method, cisplatin and photosensitizers were encapsulated inside nanoparticles. Meanwhile, the targeting peptide cRGD and targeting molecule folate can be modified on the surface of nanoparticles to realize the active identification of tumor cells. The measurements of dynamic light scattering showed that the prepared nanoparticles had an ideal dispersibility and uniform particle size of 102.6 nm. On the basis of the results observed from confocal laser scanning microscope, the modified nanoparticles were more efficient endocytosed by MCF-7 cells as a contrast to SGC-7901 cells. Photothermal conversion-triggered drug release and photo-therapies produced a significant apoptosis rate of 85.9% on MCF-7 cells. The distinguished results made it believed that the formulated delivery system had conducted great efforts and innovations for the realization of concise collaboration and provided a promising strategy for the treatment of breast cancer.

  20. Bioactive Glass Nanoparticles as a New Delivery System for Sustained 5-Fluorouracil Release: Characterization and Evaluation of Drug Release Mechanism

    Directory of Open Access Journals (Sweden)

    Abeer M. El-Kady

    2015-01-01

    Full Text Available Bioactive glass nanoparticles were synthesized and tested for the first time as a new delivery system for sustained 5-fluorouracil (5-FU release. They were characterized by TEM, DTA, TGA, and FT-IR. The porosity % and specific surface area of glass nanoparticles were 85.59% and 378.36 m2/g, respectively. The in vitro bioactivity evaluation confirmed that bioactive glass disks prepared from these nanoparticles could induce hydroxyapatite layer over their surfaces in simulated body fluid. The in vitro drug release experiment indicated that glass nanoparticles could serve as long-term local delivery vehicles for sustained 5-FU release. The release profile of 5-FU showed an initial fast release stage followed by a second stage of slower release. The initial burst release of 5-FU in the first day was about 23% (28.92 mg·L−1 of the total amount of loaded 5-FU, while the final cumulative percentage of the 5-FU released after 32 days was about 45.6% (57.31 mg·L−1 of the total amount of loaded 5-FU. The application of different mathematical models indicated that 5-FU was released by diffusion controlled mechanism and suggested that its release rate was dependent on glass particles dissolution, changes of surface area as well as diameter of glass particles, and concentration of loaded drug.

  1. Delivery of Gemcitabine Prodrugs Employing Mesoporous Silica Nanoparticles

    Directory of Open Access Journals (Sweden)

    Alessio Malfanti

    2016-04-01

    Full Text Available In this paper, mesoporous silica nanoparticles (MSNs were studied as vehicles for the delivery of the antitumoral drug gemcitabine (GEM and of its 4-(N-acyl derivatives, (4-(N-valeroyl-(C5GEM, 4-(N-lauroyl-(C12GEM and 4-(N-stearoyl-gemcitabine (C18GEM. The loading of the GEM lipophilic prodrugs on MSNs was explored with the aim to obtain both a physical and a chemical protection of GEM from rapid plasmatic metabolization. For this purpose, MSNs as such or with grafted aminopropyl and carboxyethyl groups were prepared and characterized. Then, their different drug loading capacity in relation to the nature of the functional group was evaluated. In our experimental conditions, GEM was not loaded in any MSNs, while C12GEM was the most efficiently encapsulated and employed for further evaluation. The results showed that loading capacity increased with the presence of functional groups on the nanoparticles; similarly, the presence of functional groups on MSNs’ surface influenced the drug release profile. Finally, the cytotoxicity of the different preparations was evaluated and data showed that C12GEM loaded MSNs are less cytotoxic than the free drug with an activity that increased with the incubating time, indicating that all these systems are able to release the drug in a controlled manner. Altogether, the results demonstrate that these MSNs could be an interesting system for the delivery of anticancer drugs.

  2. Solid lipid nanoparticles suspension versus commercial solutions for dermal delivery of minoxidil.

    Science.gov (United States)

    Padois, Karine; Cantiéni, Céline; Bertholle, Valérie; Bardel, Claire; Pirot, Fabrice; Falson, Françoise

    2011-09-15

    Solid lipid nanoparticles have been reported as possible carrier for skin drug delivery. Solid lipid nanoparticles are produced from biocompatible and biodegradable lipids. Solid lipid nanoparticles made of semi-synthetic triglycerides stabilized with a mixture of polysorbate and sorbitan oleate were loaded with 5% of minoxidil. The prepared systems were characterized for particle size, pH and drug content. Ex vivo skin penetration studies were performed using Franz-type glass diffusion cells and pig ear skin. Ex vivo skin corrosion studies were realized with a method derived from the Corrositex(®) test. Solid lipid nanoparticles suspensions were compared to commercial solutions in terms of skin penetration and skin corrosion. Solid lipid nanoparticles suspensions have been shown as efficient as commercial solutions for skin penetration; and were non-corrosive while commercial solutions presented a corrosive potential. Solid lipid nanoparticles suspensions would constitute a promising formulation for hair loss treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Chitosan-Based Nanoparticles for Mucosal Delivery of RNAi Therapeutics

    DEFF Research Database (Denmark)

    Martirosyan, Alina; Olesen, Morten Jarlstad; Howard, Kenneth A.

    2014-01-01

    of the polysaccharide chitosan have been used to facilitate delivery of siRNA across mucosal surfaces following local administration. This chapter describes the mucosal barriers that need to be addressed in order to design an effective mucosal delivery strategy and the utilization of the mucoadhesive properties...... of chitosan. Focus is given to preparation methods and the preclinical application of chitosan nanoparticles for respiratory and oral delivery of siRNA....

  4. Thiolated chitosan nanoparticles as a delivery system for antisense therapy: evaluation against EGFR in T47D breast cancer cells.

    Science.gov (United States)

    Talaei, Fatemeh; Azizi, Ebrahim; Dinarvand, Rassoul; Atyabi, Fatemeh

    2011-01-01

    Thiolated chitosan has high transfection and mucoadhesive properties. We investigated the potential of two recently synthesized polymers: NAC-C (N-acetyl cysteine-chitosan) and NAP-C (N-acetyl penicillamine-chitosan) in anticancer drug delivery targeting epidermal growth factor receptor (EGFR). Doxorubicin (DOX) and antisense oligonucleotide (ASOND)-loaded polymer nanoparticles were prepared in water by a gelation process. Particle characterization, drug loading, and drug release were evaluated. To verify drug delivery efficiency in vitro experiments on a breast cancer cell line (T47D) were performed. EGFR gene and protein expression was analyzed by real time quantitative polymerase chain reaction and Western blotting, respectively. A loading percentage of 63% ± 5% for ASOND and 70% ± 5% for DOX was achieved. Drug release data after 15 hours showed that ASOND and DOX were completely released from chitosan-based particles while a lower and more sustained release of only 22% ± 8% was measured for thiolated particles. In a cytosol simulated release medium/reducing environment, such as found intracellularly, polymer-based nanoparticles dissociated, liberating approximately 50% of both active substances within 7 hours. ASOND-loaded polymer nanoparticles had higher stability and high mucoadhesive properties. The ASOND-loaded thiolated particles significantly suppressed EGFR gene expression in T47D cells compared with ASOND-loaded chitosan particles and downregulated EGFR protein expression in cells. This study could facilitate future investigations into the functionality of NAP-C and NAC-C polymers as an efficient ASOND delivery system in vitro and in vivo.

  5. miR-221 suppression through nanoparticle-based miRNA delivery system for hepatocellular carcinoma therapy and its diagnosis as a potential biomarker.

    Science.gov (United States)

    Li, Feng; Wang, Feiran; Zhu, Changlai; Wei, Qun; Zhang, Tianyi; Zhou, You Lang

    2018-01-01

    MicroRNA-221(miR-221) is frequently dysregulated in cancer. The purpose of this study was to explore whether miR-221 can be used as a potential diagnostic marker or therapeutic target for hepatocellular carcinoma (HCC). In this study, we investigated whether miR-221 expression was associated with clini-copathological characteristics and prognosis in HCC patients, and we developed a nanoparticle-based miRNA delivery system and detected its therapeutic efficacy in vitro and in vivo. We found that miR-221 was upregulated in HCC tissues, cell lines and blood of HCC patients. Upregulated miR-221 was associated with clinical TNM stage and tumor capsular infiltration, and showed poor prognosis, suggesting that its suppression could serve as an effective approach for hepatocellular carcinoma therapy. Treatment of HCC cells with nanoparticle/miR-221 inhibitor complexes suppressed their growth, colony formation ability, migration and invasion. In vivo, the growth of the tumors treated by the nanoparticle/miR-221 inhibitor complexes were significantly less than those treated by the nanoparticle/miRNA scramble complexes. In addition, circulating miR-221 may act as a potential tumor biomarker for early diagnosis of HCC, and combined serum miR-221 and AFP detection gave a better performance than individual detection in early diagnosis of HCC. These findings suggest that a nanoparticle-based miRNA delivery system could potentially serve as a safe and effective treatment and miR-221 could also be a potential diagnostic marker for HCC.

  6. Delivery of rifampicin-chitin nanoparticles into the intracellular compartment of polymorphonuclear leukocytes.

    Science.gov (United States)

    Smitha, K T; Nisha, N; Maya, S; Biswas, Raja; Jayakumar, R

    2015-03-01

    Polymorphonuclear leukocytes (PMNs) provide the primary host defence against invading pathogens by producing reactive oxygen species (ROS) and microbicidal products. However, few pathogens can survive for a prolonged period of time within the PMNs. Additionally their intracellular lifestyle within the PMNs protect themselves from the additional lethal action of host immune systems such as antibodies and complements. Antibiotic delivery into the intracellular compartments of PMNs is a major challenge in the field of infectious diseases. In order to deliver antibiotics within the PMNs and for the better treatment of intracellular bacterial infections we synthesized rifampicin (RIF) loaded amorphous chitin nanoparticles (RIF-ACNPs) of 350±50 nm in diameter. RIF-ACNPs nanoparticles are found to be non-hemolytic and non-toxic against a variety of host cells. The release of rifampicin from the prepared nanoparticles was ∼60% in 24 h, followed by a sustained pattern till 72 h. The RIF-ACNPs nanoparticles showed 5-6 fold enhanced delivery of RIF into the intracellular compartments of PMNs. The RIF-ACNPs showed anti-microbial activity against Escherichia coli, Staphylococcus aureus and a variety of other bacteria. In summary, our results suggest that RIF-ACNPs could be used to treat a variety of intracellular bacterial infections. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Dendrimer-magnetic nanoparticles as multiple stimuli responsive and enzymatic drug delivery vehicle

    International Nuclear Information System (INIS)

    Chandra, Sudeshna; Noronha, Glen; Dietrich, Sascha; Lang, Heinrich; Bahadur, Dhirendra

    2015-01-01

    Two different chain lengths of (poly)ethylene glycol-PAMAM dendrimers namely, L6-PEG-PAMAM and S6-PEG-PAMAM with six end-grafted ethylene glycol ether-tentacles of type CH 2 CH 2 C(O)O(CH 2 CH 2 O) 9 CH 3 and CH 2 CH 2 C(O)O(CH 2 CH 2 O) 2 C 2 H 5 , respectively, were synthesized. These dendrimers have multiple σ-donor capabilities and therefore, were used for stabilizing the magnetite (Fe 3 O 4 ) nanoparticles. Both the dendrimer-magnetic nanoparticles (L6-PEG-PAMAM-MNPs and S6-PEG-PAMAM-MNPs) were characterized by different spectroscopic and microstructural techniques. The nanoparticles were mesoporous and superparamagnetic and therefore, explored for their possible use in delivery of cancer drug, doxorubicin (DOX). In the developed drug delivery system, achieving high drug-loading efficiency with controllable release were the main challenges. The change in zeta potential and quenching of fluorescence intensity suggests chemical interaction between DOX and the nanoparticles. The loading efficiency was calculated to be over 95% with a sustained pH and temperature sensitive release. Further, enzyme cathepsin B has also been used to degrade the dendritic shell to trigger sustained drug release in the vicinity of tumor cells

  8. Nanoscale Nutrient Delivery Systems for Food Applications: Improving Bioactive Dispersibility, Stability, and Bioavailability.

    Science.gov (United States)

    McClements, David Julian

    2015-07-01

    There has been a surge of interest in the development of nanoscale systems for the encapsulation, protection, and delivery of lipophilic nutrients, vitamins, and nutraceuticals. This review article highlights the challenges associated with incorporating these lipophilic bioactive components into foods, and then discusses potential nanoscale delivery systems that can be used to overcome these challenges. In particular, the desirable characteristics required for any nanoscale delivery system are presented, as well as methods of fabricating them and of characterizing them. An overview of different delivery systems is given, such as microemulsions, nanoemulsions, emulsions, microgels, and biopolymer nanoparticles, and their potential applications are discussed. Nanoscale delivery systems have considerable potential within the food industry, but they must be carefully formulated to ensure that they are safe, economically viable, and effective. Nanoscale delivery systems have numerous potential applications in the food industry for encapsulating, protecting, and releasing bioactive agents, such as nutraceuticals and vitamins. This review article highlights methods for designing, fabricating, characterizing, and utilizing edible nanoparticles from a variety of different food-grade ingredients. © 2015 Institute of Food Technologists®

  9. An efficient targeted drug delivery through apotransferrin loaded nanoparticles.

    Directory of Open Access Journals (Sweden)

    Athuluri Divakar Sai Krishna

    Full Text Available BACKGROUND: Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules. The present study demonstrates the specificity and efficacy of protein nanoparticle of apotransferrin for targeted delivery of doxorubicin. METHODOLOGY/PRINCIPAL FINDINGS: Apotransferrin nanoparticles were developed by sol-oil chemistry. A comparative analysis of efficiency of drug delivery in conjugated and non-conjugated forms of doxorubicin to apotransferrin nanoparticle is presented. The spherical shaped apotransferrin nanoparticles (nano have diameters of 25-50 etam, which increase to 60-80 etam upon direct loading of drug (direct-nano, and showed further increase in dimension (75-95 etam in conjugated nanoparticles (conj-nano. The competitive experiments with the transferrin receptor specific antibody showed the entry of both conj-nano and direct-nano into the cells through transferrin receptor mediated endocytosis. Results of various studies conducted clearly establish the superiority of the direct-nano over conj-nano viz. (a localization studies showed complete release of drug very early, even as early as 30 min after treatment, with the drug localizing in the target organelle (nucleus (b pharmacokinetic studies showed enhanced drug concentrations, in circulation with sustainable half-life (c the studies also demonstrated efficient drug delivery, and an enhanced inhibition of proliferation in cancer cells. Tissue distribution analysis showed intravenous administration of direct nano lead to higher drug localization in liver, and blood as compared to relatively lesser localization in heart, kidney and spleen. Experiments using rat cancer model confirmed the efficacy of the formulation in

  10. Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents

    Directory of Open Access Journals (Sweden)

    Rouhani H

    2011-04-01

    Full Text Available R Dinarvand1,2, N Sepehri1, S Manoochehri1, H Rouhani1, F Atyabi1,21Department of Pharmaceutics, Faculty of Pharmacy, 2Nanotechnology Research Centre, Tehran University of Medical Sciences, Tehran, IranAbstract: The effectiveness of anticancer agents may be hindered by low solubility in water, poor permeability, and high efflux from cells. Nanomaterials have been used to enable drug delivery with lower toxicity to healthy cells and enhanced drug delivery to tumor cells. Different nanoparticles have been developed using different polymers with or without surface modification to target tumor cells both passively and/or actively. Polylactide-co-glycolide (PLGA, a biodegradable polyester approved for human use, has been used extensively. Here we report on recent developments concerning PLGA nanoparticles prepared for cancer treatment. We review the methods used for the preparation and characterization of PLGA nanoparticles and their applications in the delivery of a number of active agents. Increasing experience in the field of preparation, characterization, and in vivo application of PLGA nanoparticles has provided the necessary momentum for promising future use of these agents in cancer treatment, with higher efficacy and fewer side effects.Keywords: nanotechnology, polymeric nanocarriers, targeting, anticancer agents, surface modification

  11. Folate-containing reduction-sensitive lipid-polymer hybrid nanoparticles for targeted delivery of doxorubicin.

    Science.gov (United States)

    Wu, Bo; Yu, Ping; Cui, Can; Wu, Ming; Zhang, Yang; Liu, Lei; Wang, Cai-Xia; Zhuo, Ren-Xi; Huang, Shi-Wen

    2015-04-01

    The development and evaluation of folate-targeted and reduction-triggered biodegradable nanoparticles are introduced to the research on targeted delivery of doxorubicin (DOX). This type of folate-targeted lipid-polymer hybrid nanoparticles (FLPNPs) is comprised of a poly(D,L-lactide-co-glycolide) (PLGA) core, a soybean lecithin monolayer, a monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16) reduction-sensitive shell, and a folic acid-targeted ligand. FLPNPs exhibited high size stability but fast disassembly in a simulated cancer cell reductive environment. The experiments on the release process in vitro revealed that as a reduction-sensitive drug delivery system, FLPNPs released DOX faster in the presence of 10 mM dithiothreitol (DTT). Results from flow cytometry, confocal image and in vitro cytotoxicity assays revealed that FLPNPs further enhanced cell uptake and generated higher cytotoxicity against human epidermoid carcinoma in the oral cavity than non-targeted redox-sensitive and targeted redox-insensitive controls. Furthermore, in vivo animal experiments demonstrated that systemic administration of DOX-loaded FLPNPs remarkably reduced tumor growth. Experiments on biodistribution of DOX-loaded FLPNPs showed that an increasing amount of DOX accumulated in the tumor. Therefore, FLPNPs formulations have proved to be a stable, controllable and targeted anticancer drug delivery system.

  12. Delivery of proteins to mammalian cells via gold nanoparticle mediated laser transfection

    International Nuclear Information System (INIS)

    Heinemann, D; Kalies, S; Schomaker, M; Ertmer, W; Meyer, H; Ripken, T; Murua Escobar, H

    2014-01-01

    Nanoparticle laser interactions are in widespread use in cell manipulation. In particular, molecular medicine needs techniques for the directed delivery of molecules into mammalian cells. Proteins are the final mediator of most cellular cascades. However, despite several methodical approaches, the efficient delivery of proteins to cells remains challenging. This paper presents a new protein transfection technique via laser scanning of cells previously incubated with gold nanoparticles. The laser-induced plasmonic effects on the gold nanoparticles cause a transient permeabilization of the cellular membrane, allowing proteins to enter the cell. Applying this technique, it was possible to deliver green fluorescent protein into mammalian cells with an efficiency of 43%, maintaining a high level of cell viability. Furthermore, a functional delivery of Caspase 3, an apoptosis mediating protein, was demonstrated and evaluated in several cellular assays. Compared to conventional protein transfection techniques such as microinjection, the methodical approach presented here enables high-throughput transfection of about 10 000 cells per second. Moreover, a well-defined point in time of delivery is guaranteed by gold nanoparticle mediated laser transfection, allowing the detailed temporal analysis of cellular pathways and protein trafficking. (papers)

  13. Current and emerging lipid-based systems for transdermal drug delivery.

    Science.gov (United States)

    Singla, Sumeet K; Sachdeva, Vishal

    2015-01-01

    Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.

  14. Membrane-Mimic Nanoparticles for Drug and Gene Delivery

    KAUST Repository

    Alamoudi, Kholod

    2017-01-01

    -mimic nanoparticles are considered highly attractive materials for in vivo and in vitro applications. Synthetic membrane vesicles (liposomes) and nanoconstructs built with native cancer cellular membrane are excellent scaffolds to improve cellular delivery. Liposomes

  15. Designing synthetic RNA for delivery by nanoparticles

    International Nuclear Information System (INIS)

    Jedrzejczyk, Dominika; Pawlowska, Roza; Chworos, Arkadiusz; Gendaszewska-Darmach, Edyta

    2017-01-01

    The rapid development of synthetic biology and nanobiotechnology has led to the construction of various synthetic RNA nanoparticles of different functionalities and potential applications. As they occur naturally, nucleic acids are an attractive construction material for biocompatible nanoscaffold and nanomachine design. In this review, we provide an overview of the types of RNA and nucleic acid’s nanoparticle design, with the focus on relevant nanostructures utilized for gene-expression regulation in cellular models. Structural analysis and modeling is addressed along with the tools available for RNA structural prediction. The functionalization of RNA-based nanoparticles leading to prospective applications of such constructs in potential therapies is shown. The route from the nanoparticle design and modeling through synthesis and functionalization to cellular application is also described. For a better understanding of the fate of targeted RNA after delivery, an overview of RNA processing inside the cell is also provided. (topical review)

  16. Preparation and characterization of β-cyclodextrin grafted N-maleoyl chitosan nanoparticles for drug delivery

    Directory of Open Access Journals (Sweden)

    Xinyu Hou

    2017-11-01

    Full Text Available β-cyclodextrin (CD grafted N-maleoyl chitosan (CD-g-NMCS with two different degrees of substitution (DS of N-maleoyl (DS = 21.2% and 30.5% were synthesized from maleic anhydride and chitosan bearing pendant cyclodextrin (CD-g-CS. CD-g-NMCS based nanoparticles were prepared via an ionic gelation method together with chitosan and CD-g-CS nanoparticles. The size and zeta potential of prepared CD-g-NMCS nanoparticles were 179.2~274.0 nm and 36.2~42.4 mV, respectively. In vitro stability test indicated that CD-g-NMCS nanoparticles were more stable in phosphate-buffered saline compared with chitosan nanoparticles. Moreover, a poorly water-soluble drug, ketoprofen (KTP, was selected as a model drug to study the obtained nanoparticle's potentials as drug delivery carriers. The drug loading efficiency of CD-g-NMCS20 nanoparticles were 14.8% for KTP. MTT assay showed that KTP loaded CD-g-NMCS nanoparticles were safe drug carriers. Notably, in vitro drug release studies showed that KTP was released in a sustained-release manner for the nanoparticles. The pharmacokinetic of drug loaded CD-g-NMCS20 nanoparticles were evaluated in rats after intravenous administration. The results of studies revealed that, compared with free KTP, KTP loaded CD-g-NMCS20 nanoparticles exhibited a significant increase in AUC0→24h and mean residence time by 6.6-fold and 2.9-fold, respectively. Therefore, CD-g-NMCS nanoparticles could be used as a novel promising nanoparticle-based drug delivery system for sustained release of poorly water-soluble drugs. The carboxylic acid groups of the CD-g-NMCS molecule provide convenient sites for further structural modifications including introduction of tissue- or disease- specific targeting groups.

  17. Photopolymerization Synthesis of Magnetic Nanoparticle Embedded Nanogels for Targeted Biotherapeutic Delivery

    Science.gov (United States)

    Denmark, Daniel J.

    materials. Herein, a low-cost, scalable, and rapid, custom ultraviolet photo-reactor with in-situ, spectroscopic monitoring system is used to observe the synthesis as the sample undergoes photopolymerization. This method also allows in-situ encapsulation of the magnetic nanoparticles simplifying the process. Size characterization of the resulting nanogels was performed by Transmission Electron Microscopy revealing size-tunable nanogel spheres between 50 and 800 nm by varying the ratio and concentration of the reactants. Nano-Tracking Analysis indicates that the nanogels exhibit minimal agglomeration as well as provides a temperature-dependent particle size distribution. Optical characterization utilized Fourier Transform Infrared and Ultraviolet Spectroscopy to confirm successful polymerization. When samples of the nanogels encapsulating magnetic nanoparticles were subjected to an alternating magnetic field a temperature increase was observed indicating that triggered release is possible. Furthermore, a model, based on linear response theory that innovatively utilizes size distribution data, is presented to explain alternating magnetic field heating results. The results presented here will advance targeted biotherapeutic delivery and have a wide range of applications in medical sciences like oncology, gene delivery, cardiology and endocrinology.

  18. A sight on the current nanoparticle-based gene delivery vectors

    Science.gov (United States)

    Dizaj, Solmaz Maleki; Jafari, Samira; Khosroushahi, Ahmad Yari

    2014-05-01

    Nowadays, gene delivery for therapeutic objects is considered one of the most promising strategies to cure both the genetic and acquired diseases of human. The design of efficient gene delivery vectors possessing the high transfection efficiencies and low cytotoxicity is considered the major challenge for delivering a target gene to specific tissues or cells. On this base, the investigations on non-viral gene vectors with the ability to overcome physiological barriers are increasing. Among the non-viral vectors, nanoparticles showed remarkable properties regarding gene delivery such as the ability to target the specific tissue or cells, protect target gene against nuclease degradation, improve DNA stability, and increase the transformation efficiency or safety. This review attempts to represent a current nanoparticle based on its lipid, polymer, hybrid, and inorganic properties. Among them, hybrids, as efficient vectors, are utilized in gene delivery in terms of materials (synthetic or natural), design, and in vitro/ in vivo transformation efficiency.

  19. Application of polymeric nanoparticles and micelles in insulin oral delivery

    Directory of Open Access Journals (Sweden)

    Milind Sadashiv Alai

    2015-09-01

    Full Text Available Diabetes mellitus is an endocrine disease in which the pancreas does not produce sufficient insulin or the body cannot effectively use the insulin it produces. Insulin therapy has been the best choice for the clinical management of diabetes mellitus. The current insulin therapy is via subcutaneous injection, which often fails to mimic the glucose homeostasis that occurs in normal individuals. This provokes numerous attempts to develop a safe and effective noninvasive route for insulin delivery. Oral delivery is the most convenient administration route. However, insulin cannot be well absorbed orally because of its rapid enzymatic degradation in the gastrointestinal tract. Therefore, nanoparticulate carriers such as polymeric nanoparticles and micelles are employed for the oral delivery of insulin. These nanocarriers protect insulin from degradation and facilitate insulin uptake via a transcellular and/or paracellular pathway. This review article focuses on the application of nanoparticles and micelles in insulin oral delivery. The recent advances in this topic are also reviewed.

  20. Gadolinium-Doped Gallic Acid-Zinc/Aluminium-Layered Double Hydroxide/Gold Theranostic Nanoparticles for a Bimodal Magnetic Resonance Imaging and Drug Delivery System

    Science.gov (United States)

    Sani Usman, Muhammad; Hussein, Mohd Zobir; Fakurazi, Sharida; Ahmad Saad, Fathinul Fikri

    2017-01-01

    We have developed gadolinium-based theranostic nanoparticles for co-delivery of drug and magnetic resonance imaging (MRI) contrast agent using Zn/Al-layered double hydroxide as the nanocarrier platform, a naturally occurring phenolic compound, gallic acid (GA) as therapeutic agent, and Gd(NO3)3 as diagnostic agent. Gold nanoparticles (AuNPs) were grown on the system to support the contrast for MRI imaging. The nanoparticles were characterized using techniques such as Hi-TEM, XRD, ICP-ES. Kinetic release study of the GA from the nanoparticles showed about 70% of GA was released over a period of 72 h. The in vitro cell viability test for the nanoparticles showed relatively low toxicity to human cell lines (3T3) and improved toxicity on cancerous cell lines (HepG2). A preliminary contrast property test of the nanoparticles, tested on a 3 Tesla MRI machine at various concentrations of GAGZAu and water (as a reference) indicates that the nanoparticles have a promising dual diagnostic and therapeutic features to further develop a better future for clinical remedy for cancer treatment. PMID:28858229

  1. Gadolinium-Doped Gallic Acid-Zinc/Aluminium-Layered Double Hydroxide/Gold Theranostic Nanoparticles for a Bimodal Magnetic Resonance Imaging and Drug Delivery System.

    Science.gov (United States)

    Sani Usman, Muhammad; Hussein, Mohd Zobir; Fakurazi, Sharida; Masarudin, Mas Jaffri; Ahmad Saad, Fathinul Fikri

    2017-08-31

    We have developed gadolinium-based theranostic nanoparticles for co-delivery of drug and magnetic resonance imaging (MRI) contrast agent using Zn/Al-layered double hydroxide as the nanocarrier platform, a naturally occurring phenolic compound, gallic acid (GA) as therapeutic agent, and Gd(NO₃)₃ as diagnostic agent. Gold nanoparticles (AuNPs) were grown on the system to support the contrast for MRI imaging. The nanoparticles were characterized using techniques such as Hi-TEM, XRD, ICP-ES. Kinetic release study of the GA from the nanoparticles showed about 70% of GA was released over a period of 72 h. The in vitro cell viability test for the nanoparticles showed relatively low toxicity to human cell lines (3T3) and improved toxicity on cancerous cell lines (HepG2). A preliminary contrast property test of the nanoparticles, tested on a 3 Tesla MRI machine at various concentrations of GAGZAu and water (as a reference) indicates that the nanoparticles have a promising dual diagnostic and therapeutic features to further develop a better future for clinical remedy for cancer treatment.

  2. Lipid-polymer hybrid nanoparticles as a new generation therapeutic delivery platform: a review.

    Science.gov (United States)

    Hadinoto, Kunn; Sundaresan, Ajitha; Cheow, Wean Sin

    2013-11-01

    Lipid-polymer hybrid nanoparticles (LPNs) are core-shell nanoparticle structures comprising polymer cores and lipid/lipid-PEG shells, which exhibit complementary characteristics of both polymeric nanoparticles and liposomes, particularly in terms of their physical stability and biocompatibility. Significantly, the LPNs have recently been demonstrated to exhibit superior in vivo cellular delivery efficacy compared to that obtained from polymeric nanoparticles and liposomes. Since their inception, the LPNs have advanced significantly in terms of their preparation strategy and scope of applications. Their preparation strategy has undergone a shift from the conceptually simple two-step method, involving preformed polymeric nanoparticles and lipid vesicles, to the more principally complex, yet easier to perform, one-step method, relying on simultaneous self-assembly of the lipid and polymer, which has resulted in better products and higher production throughput. The scope of LPNs' applications has also been extended beyond single drug delivery for anticancer therapy, to include combinatorial and active targeted drug deliveries, and deliveries of genetic materials, vaccines, and diagnostic imaging agents. This review details the current state of development for the LPNs preparation and applications from which we identify future research works needed to bring the LPNs closer to its clinical realization. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Mesoporous Silica Nanoparticle-Coated Microneedle Arrays for Intradermal Antigen Delivery.

    Science.gov (United States)

    Tu, Jing; Du, Guangsheng; Reza Nejadnik, M; Mönkäre, Juha; van der Maaden, Koen; Bomans, Paul H H; Sommerdijk, Nico A J M; Slütter, Bram; Jiskoot, Wim; Bouwstra, Joke A; Kros, Alexander

    2017-08-01

    To develop a new intradermal antigen delivery system by coating microneedle arrays with lipid bilayer-coated, antigen-loaded mesoporous silica nanoparticles (LB-MSN-OVA). Synthesis of MSNs with 10-nm pores was performed and the nanoparticles were loaded with the model antigen ovalbumin (OVA), and coated with a lipid bilayer (LB-MSN-OVA). The uptake of LB-MSN-OVA by bone marrow-derived dendritic cells (BDMCs) was studied by flow cytometry. The designed LB-MSN-OVA were coated onto pH-sensitive pyridine-modified microneedle arrays and the delivery of LB-MSN-OVA into ex vivo human skin was studied. The synthesized MSNs demonstrated efficient loading of OVA with a maximum loading capacity of about 34% and the lipid bilayer enhanced the colloidal stability of the MSNs. Uptake of OVA loaded in LB-MSN-OVA by BMDCs was higher than that of free OVA, suggesting effective targeting of LB-MSN-OVA to antigen-presenting cells. Microneedles were readily coated with LB-MSN-OVA at pH 5.8, yielding 1.5 μg of encapsulated OVA per microneedle array. Finally, as a result of the pyridine modification, LB-MSN-OVA were effectively released from the microneedles upon piercing the skin. Microneedle arrays coated with LB-MSN-OVA were successfully developed and shown to be suitable for intradermal delivery of the encapsulated protein antigen.

  4. Folate-decorated chitosan/doxorubicin poly(butyl)cyanoacrylate nanoparticles for tumor-targeted drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Duan Jinghua [Xiangya Hospital, Central South University, Hepatobiliary and Enteric Surgery Research Center (China); Liu Mujun [Central South University, School of Biological Science and Technology (China); Zhang Yangde; Zhao Jinfeng; Pan Yifeng [Xiangya Hospital, Central South University, Hepatobiliary and Enteric Surgery Research Center (China); Yang Xiyun, E-mail: bax_2007@126.com [Central South University, School of Metallurgical Science and Engineering (China)

    2012-03-15

    A novel chitosan coated poly(butyl cyanoacrylate) (PBCA) nanoparticles loaded doxorubicin (DOX) were synthesized and then conjugated with folic acid to produce a folate-targeted drug carrier for tumor-specific drug delivery. Prepared nanoparticles were surface modified by folate for targeting cancer cells, which is confirmed by FTIR spectroscopy and characterized for shape, size, and zeta potential measurements. The size and zeta potential of prepared DOX-PBCA nanoparticles (DOX-PBCA NPs) were almost 174 {+-} 8.23 nm and +23.14 {+-} 4.25 mV, respectively with 46.8 {+-} 3.32% encapsulation capacity. The transmission electron microscopy study revealed that preparation allowed the formation of spherical nanometric and homogeneous. Fluorescent microscopy imaging and flow cytometry analysis revealed that DOX-PBCA NPs were endocytosed into MCF-7 cells through the interaction with overexpressed folate receptors on the surface of the cancer cells. The results demonstrate that folate-conjugated DOX-PBCA NPs drug delivery system could provide increased therapeutic benefit by delivering the encapsulated drug to the folate receptor positive cancer cells.

  5. Biosynthesis of insulin-silk fibroin nanoparticles conjugates and in vitro evaluation of a drug delivery system

    Science.gov (United States)

    Yan, Hai-Bo; Zhang, Yu-Qing; Ma, Yong-Lei; Zhou, Li-Xia

    2009-11-01

    Silk fibroin derived from Bombyx mori is a biomacromolecular protein with outstanding biocompatibility. When it was dissolved in highly concentrated CaCl2 solution and then the mixture of the protein and salt was subjected to desalting treatments for long time in flowing water, the resulting liquid silk was water-soluble polypeptides with different molecular masses, ranging from 8 to 70 kDa. When the liquid silk was introduced rapidly into acetone, silk protein nanoparticles with a range of 40-120 nm in diameter could be obtained. The crystalline silk nanoparticles could be conjugated covalently with insulin alone with cross-linking reagent glutaraldehyde. In vitro properties of the insulin-silk fibroin nanoparticles (Ins-SFN) bioconjugates were determined by Enzyme-Linked Immunosorbent Assay (ELISA). The optimal conditions for the biosynthesis of Ins-SFN bioconjugates were investigated. The Ins-SFN constructs obtained by 8 h of covalent cross-linking with 0.7% cross-linking reagent and the proportion of insulin and SFN being 30 IU: 15 mg showed much higher recoveries (90-115%). When insulin was coupled covalently with silk nanoparticles, the resistance of the modified insulin to trypsin digestion and in vitro stability in human serum were greatly enhanced as compared with insulin alone. The results in human serum indicated that the half-life in vitro of the biosynthesized Ins-SFN derivatives was about 2.5 times more than that of native insulin. Therefore, the silk protein nanoparticles have the potential values for being studied and developed as a new bioconjugate for enzyme/polypeptide drug delivery system.

  6. Dendrimer-magnetic nanoparticles as multiple stimuli responsive and enzymatic drug delivery vehicle

    Energy Technology Data Exchange (ETDEWEB)

    Chandra, Sudeshna; Noronha, Glen [Metallurgical and Materials Science Department, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 (India); Dietrich, Sascha; Lang, Heinrich [Technische Universität Chemnitz, Institute of Chemistry, Straße der Nationen 62, d-09111 Chemnitz (Germany); Bahadur, Dhirendra, E-mail: dhirenb@iitb.ac.in [Metallurgical and Materials Science Department, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 (India)

    2015-04-15

    Two different chain lengths of (poly)ethylene glycol-PAMAM dendrimers namely, L6-PEG-PAMAM and S6-PEG-PAMAM with six end-grafted ethylene glycol ether-tentacles of type CH{sub 2}CH{sub 2}C(O)O(CH{sub 2}CH{sub 2}O){sub 9}CH{sub 3} and CH{sub 2}CH{sub 2}C(O)O(CH{sub 2}CH{sub 2}O){sub 2}C{sub 2}H{sub 5}, respectively, were synthesized. These dendrimers have multiple σ-donor capabilities and therefore, were used for stabilizing the magnetite (Fe{sub 3}O{sub 4}) nanoparticles. Both the dendrimer-magnetic nanoparticles (L6-PEG-PAMAM-MNPs and S6-PEG-PAMAM-MNPs) were characterized by different spectroscopic and microstructural techniques. The nanoparticles were mesoporous and superparamagnetic and therefore, explored for their possible use in delivery of cancer drug, doxorubicin (DOX). In the developed drug delivery system, achieving high drug-loading efficiency with controllable release were the main challenges. The change in zeta potential and quenching of fluorescence intensity suggests chemical interaction between DOX and the nanoparticles. The loading efficiency was calculated to be over 95% with a sustained pH and temperature sensitive release. Further, enzyme cathepsin B has also been used to degrade the dendritic shell to trigger sustained drug release in the vicinity of tumor cells.

  7. Nanoparticulated magnetic drug delivery systems: Preparation and magnetic characterization

    Energy Technology Data Exchange (ETDEWEB)

    Morais, P C, E-mail: pcmor@unb.b [Universidade de BrasIlia, Instituto de Fisica, Nucleo de Fisica Aplicada, Brasilia DF 70910-900 (Brazil)

    2010-03-01

    This paper describes how magnetic resonance can be successfully used as a tool to help customize and quantify nanosized magnetic particles while labeling cells and administered in animals for targeting different biological sites. Customization of magnetic nanoparticles is addressed here in terms of production of complex magnetic drug delivery systems whereas quantification of magnetic nanoparticle in different biological compartments emerges as a key experimental information to assess time-dependent magnetic nanoparticle biodistribution profiles. Examples of using magnetic resonance in unfolding information regarding the pharmacokinetics of intravenously-injected surface-functionalized magnetic nanoparticles in animals are included in the paper.

  8. BSA Nanoparticles for siRNA Delivery: Coating Effects on Nanoparticle Properties, Plasma Protein Adsorption, and In Vitro siRNA Delivery

    Directory of Open Access Journals (Sweden)

    Haran Yogasundaram

    2012-01-01

    Full Text Available Developing vehicles for the delivery of therapeutic molecules, like siRNA, is an area of active research. Nanoparticles composed of bovine serum albumin, stabilized via the adsorption of poly-L-lysine (PLL, have been shown to be potentially inert drug-delivery vehicles. With the primary goal of reducing nonspecific protein adsorption, the effect of using comb-type structures of poly(ethylene glycol (1 kDa, PEG units conjugated to PLL (4.2 and 24 kDa on BSA-NP properties, apparent siRNA release rate, cell viability, and cell uptake were evaluated. PEGylated PLL coatings resulted in NPs with ζ-potentials close to neutral. Incubation with platelet-poor plasma showed the composition of the adsorbed proteome was similar for all systems. siRNA was effectively encapsulated and released in a sustained manner from all NPs. With 4.2 kDa PLL, cellular uptake was not affected by the presence of PEG, but PEG coating inhibited uptake with 24 kDa PLL NPs. Moreover, 24 kDa PLL systems were cytotoxic and this cytotoxicity was diminished upon PEG incorporation. The overall results identified a BSA-NP coating structure that provided effective siRNA encapsulation while reducing ζ-potential, protein adsorption, and cytotoxicity, necessary attributes for in vivo application of drug-delivery vehicles.

  9. Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine.

    Science.gov (United States)

    das Neves, José; Michiels, Johan; Ariën, Kevin K; Vanham, Guido; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

    2012-06-01

    To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(ε-caprolactone) (PCL) nanoparticles containing the antiretroviral drug dapivirine. Dapivirine-loaded nanoparticles with different surface properties were produced using three surface modifiers: poloxamer 338 NF (PEO), sodium lauryl sulfate (SLS) and cetyl trimethylammonium bromide (CTAB). The ability of nanoparticles to promote intracellular drug delivery was assessed in different cell types relevant for vaginal HIV transmission/microbicide development. Also, antiretroviral activity of nanoparticles was determined in different cell models, as well as their cytotoxicity. Dapivirine-loaded nanoparticles were readily taken up by different cells, with particular kinetics depending on the cell type and nanoparticles, resulting in enhanced intracellular drug delivery in phagocytic cells. Different nanoparticles showed similar or improved antiviral activity compared to free drug. There was a correlation between increased antiviral activity and increased intracellular drug delivery, particularly when cell models were submitted to a single initial short-course treatment. PEO-PCL and SLS-PCL nanoparticles consistently showed higher selectivity index values than free drug, contrasting with high cytotoxicity of CTAB-PCL. These results provide evidence on the potential of PCL nanoparticles to affect in vitro toxicity and activity of dapivirine, depending on surface engineering. Thus, this formulation approach may be a promising strategy for the development of next generation microbicides.

  10. Cancer-targeting siRNA delivery from porous silicon nanoparticles.

    Science.gov (United States)

    Wan, Yuan; Apostolou, Sinoula; Dronov, Roman; Kuss, Bryone; Voelcker, Nicolas H

    2014-10-01

    Porous silicon nanoparticles (pSiNPs) with tunable pore size are biocompatible and biodegradable, suggesting that they are suitable biomaterials as vehicles for drug delivery. Loading of small interfering RNA (siRNA) into the pores of pSiNPs can protect siRNA from degradation as well as improve the cellular uptake. We aimed to deliver MRP1 siRNA loaded into pSiNPs to glioblastoma cells, and to demonstrate downregulation of MRP1 at the mRNA and protein levels. 50-220 nm pSiNPs with an average pore size of 26 nm were prepared, followed by electrostatic adsorption of siRNA into pores. Oligonucleotide loading and release profiles were investigated; MRP1 mRNA and protein expression, cell viability and cell apoptosis were studied. Approximately 7.7 µg of siRNA was loaded per mg of pSiNPs. Cells readily took up nanoparticles after 30 min incubation. siRNA-loaded pSiNPs were able to effectively downregulate target mRNA (~40%) and protein expression (31%), and induced cell apoptosis and necrosis (33%). siRNA loaded pSiNPs downregulated mRNA and protein expression and induced cell death. This novel siRNA delivery system may pave the way towards developing more effective tumor therapies.

  11. Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer's disease.

    Science.gov (United States)

    Muntimadugu, Eameema; Dhommati, Raju; Jain, Anjali; Challa, Venu Gopala Swami; Shaheen, M; Khan, Wahid

    2016-09-20

    Poor brain penetration of tarenflurbil (TFB) was one of the major reasons for its failure in phase III clinical trials conducted on Alzheimer's patients. Thus there is a tremendous need of developing efficient delivery systems for TFB. This study was designed with the aim of improving drug delivery to brain through intranasally delivered nanocarriers. TFB was loaded into two different nanocarriers i.e., poly (lactide-co-glycolide) nanoparticles (TFB-NPs) and solid lipid nanoparticles (TFB-SLNs). Particle size of both the nanocarriers (targeting site. Pharmacokinetics suggested improved circulation behavior of nanoparticles and the absolute bioavailabilities followed this order: TFB-NPs (i.n.)>TFB-SLNs (i.n.)>TFB solution (i.n.)>TFB suspension (oral). Brain targeting efficiency was determined in terms of %drug targeting efficiency (%DTE) and drug transport percentage (DTP). The higher %DTE (287.24) and DTP (65.18) were observed for TFB-NPs followed by TFB-SLNs (%DTE: 183.15 and DTP: 45.41) among all other tested groups. These encouraging results proved that therapeutic concentrations of TFB could be transported directly to brain via olfactory pathway after intranasal administration of polymeric and lipidic nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Prolonged Hypocalcemic Effect by Pulmonary Delivery of Calcitonin Loaded Poly(Methyl Vinyl Ether Maleic Acid Bioadhesive Nanoparticles

    Directory of Open Access Journals (Sweden)

    J. Varshosaz

    2014-01-01

    Full Text Available The purpose of the present study was to design a pulmonary controlled release system of salmon calcitonin (sCT. Therefore, poly(methyl vinyl ether maleic acid [P(MVEMA] nanoparticles were prepared by ionic cross-linking method using Fe2+ and Zn2+ ions. Physicochemical properties of nanoparticles were studied in vitro. The stability of sCT in the optimized nanoparticles was studied by electrophoretic gel method. Plasma calcium levels until 48 h were determined in rats as pulmonary-free sCT solution or nanoparticles (25 μg·kg−1, iv solution of sCT (5 μg·kg−1, and pulmonary blank nanoparticles. The drug remained stable during fabrication and tests on nanoparticles. The optimized nanoparticles showed proper physicochemical properties. Normalized reduction of plasma calcium levels was at least 2.76 times higher in pulmonary sCT nanoparticles compared to free solution. The duration of hypocalcemic effect of pulmonary sCT nanoparticles was 24 h, while it was just 1 h for the iv solution. There was not any significant difference between normalized blood calcium levels reduction in pulmonary drug solution and iv injection. Pharmacological activity of nanoparticles after pulmonary delivery was 65% of the iv route. Pulmonary delivery of P(MVEMA nanoparticles of sCT enhanced and prolonged the hypocalcemic effect of the drug significantly.

  13. Chitosan-based nanoparticles for rosmarinic acid ocular delivery--In vitro tests.

    Science.gov (United States)

    da Silva, Sara Baptista; Ferreira, Domingos; Pintado, Manuela; Sarmento, Bruno

    2016-03-01

    In this study, chitosan nanoparticles were used to encapsulate antioxidant rosmarinic acid, Salvia officinalis (sage) and Satureja montana (savory) extracts as rosmarinic acid natural vehicles. The nanoparticles were prepared by ionic gelation using chitosan and sodium tripolyphosphate (TPP) in a mass ratio of 7:1, at pH 5.8. Particle size distribution analysis and transmission electron microscopy (TEM) confirmed the size ranging from 200 to 300 nm, while surface charge of nanoparticles ranged from 20 to 30 mV. Nanoparticles demonstrate to be safe without relevant cytotoxicity against retina pigment epithelium (ARPE-19) and human cornea cell line (HCE-T). The permeability study in HCE monolayer cell line showed an apparent permeability coefficient Papp of 3.41±0.99×10(-5) and 3.24±0.79×10(-5) cm/s for rosmarinic acid loaded chitosan nanoparticles and free in solution, respectively. In ARPE-19 monolayer cell line the Papp was 3.39±0.18×10(-5) and 3.60±0.05×10(-5) cm/s for rosmarinic acid loaded chitosan nanoparticles and free in solution, respectively. Considering the mucin interaction method, nanoparticles indicate mucoadhesive proprieties suggesting an increased retention time over the ocular mucosa after instillation. These nanoparticles may be promising drug delivery systems for ocular application in oxidative eye conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Manufacturing of a Secretoneurin Drug Delivery System with Self-Assembled Protamine Nanoparticles by Titration

    Science.gov (United States)

    Scheicher, Bernhard; Lorenzer, Cornelia; Gegenbauer, Katrin; Partlic, Julia; Andreae, Fritz; Kirsch, Alexander H.; Rosenkranz, Alexander R.; Werzer, Oliver

    2016-01-01

    Since therapeutic peptides and oligonucleotides are gathering interests as active pharmaceutical ingredients (APIs), nanoparticulate drug delivery systems are becoming of great importance. Thereby, the possibility to design drug delivery systems according to the therapeutic needs of APIs enhances clinical implementation. Over the last years, the focus of our group was laid on protamine-oligonucleotide-nanoparticles (so called proticles), however, the possibility to modify the size, zeta potential or loading efficiencies was limited. Therefore, at the present study we integrated a stepwise addition of protamine (titration) into the formation process of proticles loaded with the angiogenic neuropeptide secretoneurin (SN). A particle size around 130 nm was determined when proticles were assembled by the commonly used protamine addition at once. Through application of the protamine titration process it was possible to modify and adjust the particle size between approx. 120 and 1200 nm (dependent on mass ratio) without influencing the SN loading capacity. Dynamic light scattering pointed out that the difference in particle size was most probably the result of a secondary aggregation. Initially-formed particles of early stages in the titration process aggregated towards bigger assemblies. Atomic-force-microscopy images also revealed differences in morphology along with different particle size. In contrast, the SN loading was only influenced by the applied mass ratio, where a slight saturation effect was observable. Up to 65% of deployed SN could be imbedded into the proticle matrix. An in-vivo biodistribution study (i.m.) showed a retarded distribution of SN from the site of injection after the application of a SN-proticle formulation. Further, it was demonstrated that SN loaded proticles can be successfully freeze-dried and resuspended afterwards. To conclude, the integration of the protamine titration process offers new possibilities for the formulation of proticles in

  15. Gelatin nanoparticles enhance delivery of hepatitis C virus recombinant NS2 gene.

    Science.gov (United States)

    Sabet, Salwa; George, Marina A; El-Shorbagy, Haidan M; Bassiony, Heba; Farroh, Khaled Y; Youssef, Tareq; Salaheldin, Taher A

    2017-01-01

    Development of an effective non-viral vaccine against hepatitis C virus infection is of a great importance. Gelatin nanoparticles (Gel.NPs) have an attention and promising approach as a viable carrier for delivery of vaccine, gene, drug and other biomolecules in the body. The present study aimed to develop stable Gel.NPs conjugated with nonstructural protein 2 (NS2) gene of Hepatitis C Virus genotype 4a (HCV4a) as a safe and an efficient vaccine delivery system. Gel.NPs were synthesized and characterized (size: 150±2 nm and zeta potential +17.6 mv). NS2 gene was successfully cloned and expressed into E. coli M15 using pQE-30 vector. Antigenicity of the recombinant NS2 protein was confirmed by Western blotting to verify the efficiency of NS2 as a possible vaccine. Then NS2 gene was conjugated to gelatin nanoparticles and a successful conjugation was confirmed by labeling and imaging using Confocal Laser Scanning Microscope (CLSM). Interestingly, the transformation of the conjugated NS2/Gel.NPs complex into E. coli DH5-α was 50% more efficient than transformation with the gene alone. In addition, conjugated NS2/Gel.NPs with ratio 1:100 (w/w) showed higher transformation efficiency into E. coli DH5-α than the other ratios (1:50 and 2:50). Gel.NPs effectively enhanced the gene delivery in bacterial cells without affecting the structure of NS2 gene and could be used as a safe, easy, rapid, cost-effective and non-viral vaccine delivery system for HCV.

  16. The partitioning of nanoparticles to endothelium or interstitium during ultrasound-microbubble-targeted delivery depends on peak-negative pressure

    Energy Technology Data Exchange (ETDEWEB)

    Hsiang, Y.-H.; Song, J.; Price, R. J., E-mail: rprice@virginia.edu [University of Virginia, Department of Biomedical Engineering (United States)

    2015-08-15

    Patients diagnosed with advanced peripheral arterial disease often face poor prognoses and have limited treatment options. For some patient populations, the therapeutic growth of collateral arteries (i.e. arteriogenesis) that bypass regions affected by vascular disease may become a viable treatment option. Our group and others are developing therapeutic approaches centered on the ability of ultrasound-activated microbubbles to permeabilize skeletal muscle capillaries and facilitate the targeted delivery of pro-arteriogenic growth factor-bearing nanoparticles. The development of such approaches would benefit significantly from a better understanding of how nanoparticle diameter and ultrasound peak-negative pressure affect both total nanoparticle delivery and the partitioning of nanoparticles to endothelial or interstitial compartments. Toward this goal, using Balb/C mice that had undergone unilateral femoral artery ligation, we intra-arterially co-injected nanoparticles (50 and 100 nm) with microbubbles, applied 1 MHz ultrasound to the gracilis adductor muscle at peak-negative pressures of 0.7, 0.55, 0.4, and 0.2 MPa, and analyzed nanoparticle delivery and distribution. As expected, total nanoparticle (50 and 100 nm) delivery increased with increasing peak-negative pressure, with 50 nm nanoparticles exhibiting greater tissue coverage than 100 nm nanoparticles. Of particular interest, increasing peak-negative pressure resulted in increased delivery to the interstitium for both nanoparticle sizes, but had little influence on nanoparticle delivery to the endothelium. Thus, we conclude that alterations to peak-negative pressure may be used to adjust the fraction of nanoparticles delivered to the interstitial compartment. This information will be useful when designing ultrasound protocols for delivering pro-arteriogenic nanoparticles to skeletal muscle.

  17. The partitioning of nanoparticles to endothelium or interstitium during ultrasound-microbubble-targeted delivery depends on peak-negative pressure

    International Nuclear Information System (INIS)

    Hsiang, Y.-H.; Song, J.; Price, R. J.

    2015-01-01

    Patients diagnosed with advanced peripheral arterial disease often face poor prognoses and have limited treatment options. For some patient populations, the therapeutic growth of collateral arteries (i.e. arteriogenesis) that bypass regions affected by vascular disease may become a viable treatment option. Our group and others are developing therapeutic approaches centered on the ability of ultrasound-activated microbubbles to permeabilize skeletal muscle capillaries and facilitate the targeted delivery of pro-arteriogenic growth factor-bearing nanoparticles. The development of such approaches would benefit significantly from a better understanding of how nanoparticle diameter and ultrasound peak-negative pressure affect both total nanoparticle delivery and the partitioning of nanoparticles to endothelial or interstitial compartments. Toward this goal, using Balb/C mice that had undergone unilateral femoral artery ligation, we intra-arterially co-injected nanoparticles (50 and 100 nm) with microbubbles, applied 1 MHz ultrasound to the gracilis adductor muscle at peak-negative pressures of 0.7, 0.55, 0.4, and 0.2 MPa, and analyzed nanoparticle delivery and distribution. As expected, total nanoparticle (50 and 100 nm) delivery increased with increasing peak-negative pressure, with 50 nm nanoparticles exhibiting greater tissue coverage than 100 nm nanoparticles. Of particular interest, increasing peak-negative pressure resulted in increased delivery to the interstitium for both nanoparticle sizes, but had little influence on nanoparticle delivery to the endothelium. Thus, we conclude that alterations to peak-negative pressure may be used to adjust the fraction of nanoparticles delivered to the interstitial compartment. This information will be useful when designing ultrasound protocols for delivering pro-arteriogenic nanoparticles to skeletal muscle

  18. Nanoparticle synthesis and delivery by an aerosol route for watermelon plant foliar uptake

    International Nuclear Information System (INIS)

    Wang Weining; Tarafdar, Jagadish C.; Biswas, Pratim

    2013-01-01

    An aerosol process was developed for synthesis and delivery of nanoparticles for living watermelon plant foliar uptake. This is an efficient technique capable of generating nanoparticles with controllable particle sizes and number concentrations. Aerosolized nanoparticles were easily applied to leaf surfaces and enter the stomata via gas uptake, avoiding direct interaction with soil systems, eliminating potential ecological risks. The uptake and transport of nanoparticles inside the watermelon plants were investigated systematically by various techniques, such as elemental analysis by inductively coupled plasma mass spectrometry and plant anatomy by transmission electron microscopy. The results revealed that certain fractions of nanoparticles (d p < 100 nm) generated by the aerosol process could enter the leaf following the stomatal pathway, then pass through the stem, and reach the root of the watermelon plants. The particle size and number concentration played an important role in nanoparticle translocation inside the plants. In addition, the nanoparticle application method, working environment, and leaf structure are also important factors to be considered for successful plant foliar uptake.

  19. Nanoparticle synthesis and delivery by an aerosol route for watermelon plant foliar uptake

    Energy Technology Data Exchange (ETDEWEB)

    Wang Weining [Washington University in St. Louis, Aerosol and Air Quality Research Laboratory, Department of Energy, Environmental and Chemical Engineering (United States); Tarafdar, Jagadish C. [Central Arid Zone Research Institute (India); Biswas, Pratim, E-mail: pbiswas@wustl.edu [Washington University in St. Louis, Aerosol and Air Quality Research Laboratory, Department of Energy, Environmental and Chemical Engineering (United States)

    2013-01-15

    An aerosol process was developed for synthesis and delivery of nanoparticles for living watermelon plant foliar uptake. This is an efficient technique capable of generating nanoparticles with controllable particle sizes and number concentrations. Aerosolized nanoparticles were easily applied to leaf surfaces and enter the stomata via gas uptake, avoiding direct interaction with soil systems, eliminating potential ecological risks. The uptake and transport of nanoparticles inside the watermelon plants were investigated systematically by various techniques, such as elemental analysis by inductively coupled plasma mass spectrometry and plant anatomy by transmission electron microscopy. The results revealed that certain fractions of nanoparticles (d{sub p} < 100 nm) generated by the aerosol process could enter the leaf following the stomatal pathway, then pass through the stem, and reach the root of the watermelon plants. The particle size and number concentration played an important role in nanoparticle translocation inside the plants. In addition, the nanoparticle application method, working environment, and leaf structure are also important factors to be considered for successful plant foliar uptake.

  20. Update on Nanotechnology-based Drug Delivery Systems in Cancer Treatment.

    Science.gov (United States)

    Ho, Benjamin N; Pfeffer, Claire M; Singh, Amareshwar T K

    2017-11-01

    The emerging field of nanotechnology meets the demands for innovative approaches in the diagnosis and treatment of cancer. The nanoparticles are biocompatible and biodegradable and are made of a core, a particle that acts as a carrier, and one or more functional groups on the core which target specific sites. Nanotech in drug delivery includes nanodisks, High Density Lipoprotein nanostructures, liposomes, and gold nanoparticles. The fundamental advantages of nanoparticles are: improved delivery of water-insoluble drugs, targeted delivery, co-delivery of two or more drugs for combination therapy, and visualization of the drug delivery site by combining imaging system and a therapeutic drug. One of the potential applications of nanotechnology is in the treatment of cancer. Conventional methods for cancer treatments have included chemotherapy, surgery, or radiation. Early recognition and treatment of cancer with these approaches is still challenging. Innovative technologies are needed to overcome multidrug resistance, and increase drug localization and efficacy. Application of nanotechnology to cancer biology has brought in a new hope for developing treatment strategies on cancer. In this study, we present a review on the recent advances in nanotechnology-based approaches in cancer treatment. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Photoacoustic microscopy imaging for microneedle drug delivery

    Science.gov (United States)

    Moothanchery, Mohesh; Seeni, Razina Z.; Xu, Chenjie; Pramanik, Manojit

    2018-02-01

    The recent development of novel transdermal drug delivery systems (TDDS) using microneedle technology allows micron-sized conduits to be formed within the outermost skin layers attracting keen interest in skin as an interface for localized and systemic delivery of therapeutics. In light of this, researchers are using microneedles as tools to deliver nanoparticle formulations to targeted sites for effective therapy. However, in such studies the use of traditional histological methods are employed for characterization and do not allow for the in vivo visualization of drug delivery mechanism. Hence, this study presents a novel imaging technology to characterize microneedle based nanoparticle delivery systems using optical resolution-photoacoustic microscopy (OR-PAM). In this study in vivo transdermal delivery of gold nanoparticles using microneedles in mice ear and the spatial distribution of the nanoparticles in the tissue was successfully illustrated. Characterization of parameters that are relevant in drug delivery studies such as penetration depth, efficiency of delivered gold nanoparticles were monitored using the system. Photoacoustic microscopy proves an ideal tool for the characterization studies of microneedle properties and the studies shows microneedles as an ideal tool for precise and controlled drug delivery.

  2. Novel PVA-DNA nanoparticles prepared by ultra high pressure technology for gene delivery

    International Nuclear Information System (INIS)

    Kimura, Tsuyoshi; Okuno, Akira; Miyazaki, Kozo; Furuzono, Tsutomu; Ohya, Yuichi; Ouchi, Tatsuro; Mutsuo, Shingo; Yoshizawa, Hidekazu; Kitamura, Yoshiro; Fujisato, Toshiyta; Kishida, Akio

    2004-01-01

    Polyvinyl alcohol (PVA)-DNA nanoparticles have been developed by ultra high pressure (UHP) technology. Mixture solutions of DNA and PVA having various molecular weights (Mw) and degree of saponifications (DS) were treated under 10,000 atmospheres (981 MPa) condition at 40 deg. C for 10 min. Agarose gel electrophoresis and scanning electron microscope observation revealed that the PVA-DNA nanoparticles with average diameter of about 200 nm were formed. Using PVA of higher Mw and degree of saponifications, the amount of nanoparticles formed increased. The driving force of nanoparticle formation was the hydrogen bonding between DNA and PVA. In order to apply the PVA-DNA nanoparticles for gene delivery, the cytotoxicity and the cellular uptake of them were investigated using Raw264 cell lines. The cell viability was not influenced whether the presence of the PVA-DNA nanoparticles. Further, the nanoparticles internalized into cells were observed by fluorescent microscope. These results indicates that the PVA-DNA nanoparticles prepared by UHP technology showed be useful as drug carrier, especially for gene delivery

  3. PEGylated carboxymethyl chitosan/calcium phosphate hybrid anionic nanoparticles mediated hTERT siRNA delivery for anticancer therapy.

    Science.gov (United States)

    Xie, Ying; Qiao, Hongzhi; Su, Zhigui; Chen, Minglei; Ping, Qineng; Sun, Minjie

    2014-09-01

    Lack of safe and effective delivery vehicle is the main obstacle for siRNA mediated cancer therapy. In this study, we synthesized a pH-sensitive polymer of PEG grafted carboxymethyl chitosan (PEG-CMCS) and developed anionic-charged hybrid nanoparticles of PEG-CMCS and calcium phosphate (CaP) for siRNA delivery through a single-step self-assembly method in aqueous condition. The formed nanoparticles with charge of around -8.25 mv and average diameter of 102.1 nm exhibited efficient siRNA encapsulation and enhanced colloidal and serum stability. The test in vitro indicated that the nanoparticles entered into HepG2 cells by endocytosis, and achieved endosomal escape of siRNA effectively due to the pH-responsive disassembly of nanoparticles and dissolution of CaP in the endosome. Reporter gene silencing assay showed that luciferase siRNA delivered by the anionic nanoparticles could achieve gene silencing efficacy comparable to that of conventional Lipofectamine 2000. Additionally, dramatic hTERT knockdown mediated by the anionic nanoparticles transfection induced significant apoptosis of HepG2 cells in vitro. After intravenous injection in tumor-bearing BALB/c nude mice, the nanoparticles specifically accumulated into tumor regions by EPR effect, leading to efficient and specific gene silencing sequentially. Most importantly, the nanoparticles carrying hTERT siRNA inhibited tumor growth significantly via silencing hTERT expression and inducing cells apoptosis in HepG2 tumor xenograft. Moreover, comprehensive safety studies of the nanoparticles confirmed their superior safety both in vitro and in vivo. We concluded that the PEG-CMCS/CaP hybrid anionic nanoparticles possessed potential as a safe and effective siRNA delivery system for anticancer therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. 5-Fluorouracil Encapsulated Chitosan Nanoparticles for pH-Stimulated Drug Delivery: Evaluation of Controlled Release Kinetics

    Directory of Open Access Journals (Sweden)

    R. Seda Tığlı Aydın

    2012-01-01

    Full Text Available Nanoparticles consisting of human therapeutic drugs are suggested as a promising strategy for targeted and localized drug delivery to tumor cells. In this study, 5-fluorouracil (5-FU encapsulated chitosan nanoparticles were prepared in order to investigate potentials of localized drug delivery for tumor environment due to pH sensitivity of chitosan nanoparticles. Optimization of chitosan and 5-FU encapsulated nanoparticles production revealed 148.8±1.1 nm and 243.1±17.9 nm particle size diameters with narrow size distributions, which are confirmed by scanning electron microscope (SEM images. The challenge was to investigate drug delivery of 5-FU encapsulated chitosan nanoparticles due to varied pH changes. To achieve this objective, pH sensitivity of prepared chitosan nanoparticle was evaluated and results showed a significant swelling response for pH 5 with particle diameter of ∼450 nm. In vitro release studies indicated a controlled and sustained release of 5-FU from chitosan nanoparticles with the release amounts of 29.1–60.8% due to varied pH environments after 408 h of the incubation period. pH sensitivity is confirmed by mathematical modeling of release kinetics since chitosan nanoparticles showed stimuli-induced release. Results suggested that 5-FU encapsulated chitosan nanoparticles can be launched as pH-responsive smart drug delivery agents for possible applications of cancer treatments.

  5. Self-Assembled Lipid Nanoparticles for Oral Delivery of Heparin-Coated Iron Oxide Nanoparticles for Theranostic Purposes.

    Science.gov (United States)

    Truzzi, Eleonora; Bongio, Chiara; Sacchetti, Francesca; Maretti, Eleonora; Montanari, Monica; Iannuccelli, Valentina; Vismara, Elena; Leo, Eliana

    2017-06-09

    Recently, solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their potential as an oral delivery system, promoting intestinal absorption in the lymphatic circulation which plays a role in disseminating metastatic cancer cells and infectious agents throughout the body. SLN features can be exploited for the oral delivery of theranostics. Therefore, the aim of this work was to design and characterise self-assembled lipid nanoparticles (SALNs) to encapsulate and stabilise iron oxide nanoparticles non-covalently coated with heparin (Fe@hepa) as a model of a theranostic tool. SALNs were characterised for physico-chemical properties (particle size, surface charge, encapsulation efficiency, in vitro stability, and heparin leakage), as well as in vitro cytotoxicity by methyl thiazole tetrazolium (MTT) assay and cell internalisation in CaCo-2, a cell line model used as an indirect indication of intestinal lymphatic absorption. SALNs of about 180 nm, which are stable in suspension and have a high encapsulation efficiency (>90%) were obtained. SALNs were able to stabilise the heparin coating of Fe@hepa, which are typically unstable in physiological environments. Moreover, SALNs-Fe@hepa showed no cytotoxicity, although their ability to be internalised into CaCo-2 cells was highlighted by confocal microscopy analysis. Therefore, the results indicated that SALNs can be considered as a promising tool to orally deliver theranostic Fe@hepa into the lymphatic circulation, although further in vivo studies are needed to comprehend further potential applications.

  6. Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery.

    Science.gov (United States)

    Cheng, Ru; Meng, Fenghua; Deng, Chao; Klok, Harm-Anton; Zhong, Zhiyuan

    2013-05-01

    In the past decades, polymeric nanoparticles have emerged as a most promising and viable technology platform for targeted and controlled drug delivery. As vehicles, ideal nanoparticles are obliged to possess high drug loading levels, deliver drug to the specific pathological site and/or target cells without drug leakage on the way, while rapidly unload drug at the site of action. To this end, various "intelligent" polymeric nanoparticles that release drugs in response to an internal or external stimulus such as pH, redox, temperature, magnetic and light have been actively pursued. These stimuli-responsive nanoparticles have demonstrated, though to varying degrees, improved in vitro and/or in vivo drug release profiles. In an effort to further improve drug release performances, novel dual and multi-stimuli responsive polymeric nanoparticles that respond to a combination of two or more signals such as pH/temperature, pH/redox, pH/magnetic field, temperature/reduction, double pH, pH and diols, temperature/magnetic field, temperature/enzyme, temperature/pH/redox, temperature/pH/magnetic, pH/redox/magnetic, temperature/redox/guest molecules, and temperature/pH/guest molecules have recently been developed. Notably, these combined responses take place either simultaneously at the pathological site or in a sequential manner from nanoparticle preparation, nanoparticle transporting pathways, to cellular compartments. These dual and multi-stimuli responsive polymeric nanoparticles have shown unprecedented control over drug delivery and release leading to superior in vitro and/or in vivo anti-cancer efficacy. With programmed site-specific drug delivery feature, dual and multi-stimuli responsive nanoparticulate drug formulations have tremendous potential for targeted cancer therapy. In this review paper, we highlight the recent exciting developments in dual and multi-stimuli responsive polymeric nanoparticles for precision drug delivery applications, with a particular focus

  7. Chitosan nanoparticles as drug delivery carriers for biomedical engineering

    International Nuclear Information System (INIS)

    Shi, L.E.S.; Chen, M.; XINF, L.Y.; Guo, X.F.; Zhao, L.M.

    2011-01-01

    Chitosan is a rather abundant material, which has been widely used in food industrial and bioengineering aspects, including in encapsulating active food ingredients, in enzyme immobilization, and as a carrier for drug delivery, due to its significant biological and chemical properties such as biodegradable, biocompatible, bioactive and polycationic. This review discussed preparation and applications of chitosan nanoparticles in the biomedical engineering field, namely as a drug delivery carrier for biopharmaceuticals. (author)

  8. Gold nanoparticles delivery in mammalian live cells: a critical review

    Directory of Open Access Journals (Sweden)

    Raphaël Lévy

    2010-02-01

    Full Text Available Functional nanomaterials have recently attracted strong interest from the biology community, not only as potential drug delivery vehicles or diagnostic tools, but also as optical nanomaterials. This is illustrated by the explosion of publications in the field with more than 2,000 publications in the last 2 years (4,000 papers since 2000; from ISI Web of Knowledge, ‘nanoparticle and cell’ hit. Such a publication boom in this novel interdisciplinary field has resulted in papers of unequal standard, partly because it is challenging to assemble the required expertise in chemistry, physics, and biology in a single team. As an extreme example, several papers published in physical chemistry journals claim intracellular delivery of nanoparticles, but show pictures of cells that are, to the expert biologist, evidently dead (and therefore permeable. To attain proper cellular applications using nanomaterials, it is critical not only to achieve efficient delivery in healthy cells, but also to control the intracellular availability and the fate of the nanomaterial. This is still an open challenge that will only be met by innovative delivery methods combined with rigorous and quantitative characterization of the uptake and the fate of the nanoparticles. This review mainly focuses on gold nanoparticles and discusses the various approaches to nanoparticle delivery, including surface chemical modifications and several methods used to facilitate cellular uptake and endosomal escape. We will also review the main detection methods and how their optimum use can inform about intracellular localization, efficiency of delivery, and integrity of the surface capping. Raphaël Lévy is a BBSRC David Phillips Research Fellow at the University of Liverpool. He graduated in Physics at the University Louis Pasteur in Strasbourg (France. In 2002, after a Master in Soft Condensed Matter Physics, he obtained a PhD in Physics at the University Louis Pasteur. He then moved to

  9. Solid lipid nanoparticles as insulin inhalation carriers for enhanced pulmonary delivery.

    Science.gov (United States)

    Bi, Ru; Shao, Wei; Wang, Qun; Zhang, Na

    2009-02-01

    Growing attentions have been paid to the pulmonary route for systemic delivery of peptide and protein drugs, such as insulin. Advantages of this non-injective route include rapid drug deposition in the target organ, fewer systemic side effects and avoiding first pass metabolism. However, sustained release formulations for pulmonary delivery have not been fully exploited till now. In our study, a novel dry powder inhalation (DPI) system of insulin loaded solid lipid nanoparticles (Ins-SLNs) was investigated for prolonged drug release, improved stability and effective inhalation. Firstly, the drug was incorporated into the lipid carriers for a maximum entrapment efficiency as high as 69.47 +/- 3.27% (n = 3). Secondly, DPI formulation was prepared by spray freeze drying of Ins-SLNs suspension, with optimized lyoprotectant and technique parameters in this procedure. The properties of DPI particles were characterized for their pulmonary delivery potency. Thirdly, the in vivo study of intratracheal instillation of Ins-SLNs to diabetic rats showed prolonged hypoglycemic effect and a relative pharmacological bioavailability of 44.40% could be achieved in the group of 8 IU/kg dosage. These results indicated that SLNs have shown increasing potential as an efficient and non-toxic lipophilic colloidal drug carrier for enhanced pulmonary delivery of insulin.

  10. Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.

    Science.gov (United States)

    Gunay, Mine Silindir; Ozer, A Yekta; Chalon, Sylvie

    2016-01-01

    Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.

  11. Thiolated chitosan nanoparticles as an oral delivery system for Amikacin: in vitro and ex vivo evaluations.

    Science.gov (United States)

    Atyabi, F; Talaie, F; Dinarvand, R

    2009-08-01

    The purpose of this study was the synthesis of two thiol conjugated Chitosan polymers, and evaluation of the potential of Thiomer nanoparticle formulation as a carrier for oral delivery system. Mediated by EDAC (Ethylene-3-(3-di-methylaminopropyl)-carbodiimide), either N-acetyl Cysteine (NAC) or N-acetyl D-penicillamine (NAP) were covalently attached to Chitosan. The success of the synthesis was demonstrated by comparing FTIR spectra. Iodometric titration demonstrated that depending on the pH value of the synthesis medium, the Thiomers display 250 +/- 30 microMol and 300 +/- 20 microMol thiol groups per gram of polymer respectively. The interaction between mucin and Thiomers, compared to mucin and Chitosan was studied for assessment of mucoadhesion properties of synthesized polymers. This interaction was determined by the measurement of the amount of mucin adsorbed on Chitosan and the conjugated polymers. Rotating cylinder method demonstrated an average of 20 times improvement in mucoadhesion of Thiomers compared to the unmodified polymer. Chitosan and Thiomer nanoparticles were formulated by two methods; TPP and Sodium Sulfate gelation. SEM micrographs and data achieved by a Malvern nano/zetasizer show nanoparticles formed by TPP gelation have a mean size of 150 +/- 15 nm compared to 300 +/- 25 nm sized nanoparticles obtained by Sodium sulfate gelation. TPP gelation yields smaller, more spherical shaped nanoparticles with a smaller range of size distribution. Amikacin loaded nanoparticles with an average size of 280 nm were prepared by TPP gelation in which disulfide bond formation was achieved by a time dependent oxidation process. In vitro studies were carried out; a recovery rate of 33% and a drug entrapment of 25% were achieved. The amount of release was determined during 18 hr in a carefully prepared media. The permeation time across a biological membrane was observed to be about 150 minutes. Microbiological tests were carried out on two microorganisms

  12. Evaluation of the effects of biodegradable nanoparticles on a vaccine delivery system using AFM, SEM, and TEM.

    Science.gov (United States)

    Kim, Bum-Gil; Kang, Ik-Joong

    2008-09-01

    Hepatitis B is a deadly disease, and is carried by 30% of the world's population. Antibodies are produced through a series of three manual vaccinations during infancy and childhood. However, the current needle vaccination not only induces pain in patients, but also can be inconvenient to administer. This is particularly true for the case of newborn babies. Intranasal vaccination is emerging as an alternative parenteral drug delivery method that facilitates drug delivery without causing pain. Chitosan, which is obtained through the deacetylation of chitin from crustacea, is a cationic polymer that is biodegradable, avirulent, and highly absorptive. In this study, ionic gelation between chitosan and TPP was conducted to synthesize chitosan nanoparticles with sizes of 200-400 nm and a surface potential of 55-60 mV, and which can be used as Hepatitis B vaccine carriers. Then, Hepatitis B antigen protein was impregnated to manufacture chitosan-recombinant gene vaccine protein (RGVP) nanoparticles. AFM, SEM, TEM, and STEM were used to analyze the manufactured nanoparticles, whose function as drug carriers and whose usefulness for intranasal vaccination were confirmed through in vivo tests with SD rats.

  13. Characterization of Plasmid DNA Location within Chitosan/PLGA/pDNA Nanoparticle Complexes Designed for Gene Delivery

    Directory of Open Access Journals (Sweden)

    Hali Bordelon

    2011-01-01

    Full Text Available Poly(D,L-lactide-co-glycolide- (PLGA-chitosan nanoparticles are becoming an increasingly common choice for the delivery of nucleic acids to cells for various genetic manipulation techniques. These particles are biocompatible, with tunable size and surface properties, possessing an overall positive charge that promotes complex formation with negatively charged nucleic acids. This study examines properties of the PLGA-chitosan nanoparticle/plasmid DNA complex after formation. Specifically, the study aims to determine the optimal ratio of plasmid DNA:nanoparticles for nucleic acid delivery purposes and to elucidate the location of the pDNA within these complexes. Such characterization will be necessary for the adoption of these formulations in a clinical setting. The ability of PLGA-chitosan nanoparticles to form complexes with pDNA was evaluated by using the fluorescent intercalating due OliGreen to label free plasmid DNA. By monitoring the fluorescence at different plasmid: nanoparticle ratios, the ideal plasmid:nanoparticle ration for complete complexation of plasmid was determined to be 1:50. Surface-Enhanced Raman Spectroscopy and gel digest studies suggested that even at these optimal complexation ratios, a portion of the plasmid DNA was located on the outer complex surface. This knowledge will facilitate future investigations into the functionality of the system in vitro and in vivo.

  14. Ketamine nano-delivery based on poly-lactic-co-glycolic acid (PLGA) nanoparticles

    Science.gov (United States)

    Hirano, Sota; Bovi, Michele; Romeo, Alessandro; Guzzo, Flavia; Chiamulera, Cristiano; Perduca, Massimiliano

    2018-04-01

    This work describes a novel method for the generation of a ketamine nano-delivery, to improve brain blood barrier permeability and increase drug therapeutic window as anaesthetic, analgesic and potential antidepressant. The approach herein described is based on ketamine-loaded poly-lactic-co-glycolic acid (PLGA) nanoparticles coupled to an apolipoprotein E (ApoE) peptide for delivery to the central nervous system. PLGA particles were synthesized with amount of drug, coupled with the ApoE peptide on the surface, and validated by physical characterization. The produced nanodevice showed a good colloidal stability in water, confirmed by zeta potential measurements, with a diameter in the range of 185-205 nm. The ketamine encapsulation was verified by liquid chromatography-mass spectrometry analyses obtaining an encapsulation efficiency up to 21.2 ± 3.54%. Once the occurrence of ApoE peptide functionalization was confirmed with fluorescence spectroscopy, the thermal stability and morphological information were obtained by differential scanning calorimetry and further dynamic light scattering measurements. The spherical shape and a rough nanoparticles surface were observed by atomic force microscopy. The reliability of this approach may be further developed as a protocol to be used to generate PLGA nanoparticles greater than 100 nm able to better penetrate blood brain barrier and release a neuroactive molecule at lower doses.

  15. Layer-by-layer nanoparticles as an efficient siRNA delivery vehicle for SPARC silencing.

    Science.gov (United States)

    Tan, Yang Fei; Mundargi, Raghavendra C; Chen, Min Hui Averil; Lessig, Jacqueline; Neu, Björn; Venkatraman, Subbu S; Wong, Tina T

    2014-05-14

    Efficient and safe delivery systems for siRNA therapeutics remain a challenge. Elevated secreted protein, acidic, and rich in cysteine (SPARC) protein expression is associated with tissue scarring and fibrosis. Here we investigate the feasibility of encapsulating SPARC-siRNA in the bilayers of layer-by-layer (LbL) nanoparticles (NPs) with poly(L-arginine) (ARG) and dextran (DXS) as polyelectrolytes. Cellular binding and uptake of LbL NPs as well as siRNA delivery were studied in FibroGRO cells. siGLO-siRNA and SPARC-siRNA were efficiently coated onto hydroxyapatite nanoparticles. The multilayered NPs were characterized with regard to particle size, zeta potential and surface morphology using dynamic light scattering and transmission electron microscopy. The SPARC-gene silencing and mRNA levels were analyzed using ChemiDOC western blot technique and RT-PCR. The multilayer SPARC-siRNA incorporated nanoparticles are about 200 nm in diameter and are efficiently internalized into FibroGRO cells. Their intracellular fate was also followed by tagging with suitable reporter siRNA as well as with lysotracker dye; confocal microscopy clearly indicates endosomal escape of the particles. Significant (60%) SPARC-gene knock down was achieved by using 0.4 pmole siRNA/μg of LbL NPs in FibroGRO cells and the relative expression of SPARC mRNA reduced significantly (60%) against untreated cells. The cytotoxicity as evaluated by xCelligence real-time cell proliferation and MTT cell assay, indicated that the SPARC-siRNA-loaded LbL NPs are non-toxic. In conclusion, the LbL NP system described provides a promising, safe and efficient delivery platform as a non-viral vector for siRNA delivery that uses biopolymers to enhance the gene knock down efficiency for the development of siRNA therapeutics. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Magnetic stimulus responsive vancomycin drug delivery system based on chitosan microbeads embedded with magnetic nanoparticles.

    Science.gov (United States)

    Mohapatra, Ankita; Harris, Michael A; LeVine, David; Ghimire, Madhav; Jennings, Jessica A; Morshed, Bashir I; Haggard, Warren O; Bumgardner, Joel D; Mishra, Sanjay R; Fujiwara, Tomoko

    2017-10-20

    Local antibiotic delivery can overcome some of the shortcomings of systemic therapy, such as low local concentrations and delivery to avascular sites. A localized drug delivery system (DDS), ideally, could also use external stimuli to modulate the normal drug release profile from the DDS to provide efficacious drug administration and flexibility to healthcare providers. To achieve this objective, chitosan microbeads embedded with magnetic nanoparticles were loaded with the antibiotic vancomycin and stimulated by a high frequency alternating magnetic field. Three such stimulation sessions separated by 1.5 h were applied to each test sample. The chromatographic analysis of the supernatant from these stimulated samples showed more than approximately 200% higher release of vancomycin from the DDS after the stimulation periods compared to nonstimulated samples. A 16-day long term elution study was also conducted where the DDS was allowed to elute drug through normal diffusion over a period of 11 days and stimulated on day 12 and day 15, when vancomycin level had dropped below therapeutic levels. Magnetic stimulation boosted elution of test groups above minimum inhibitory concentration (MIC), as compared to control groups (with no stimulation) which remained below MIC. The drug release from test groups in the intervals where no stimulation was given showed similar elution behavior to control groups. These results indicate promising possibilities of controlled drug release using magnetic excitation from a biopolymer-based DDS. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

  17. Organic-inorganic hybrid nanoparticles controlled delivery system for anticancer drugs.

    Science.gov (United States)

    Di Martino, Antonio; Guselnikova, Olga A; Trusova, Marina E; Postnikov, Pavel S; Sedlarik, Vladimir

    2017-06-30

    The use of organic-inorganic hybrid nanocarriers for controlled release of anticancer drugs has been gained a great interest, in particular, to improve the selectivity and efficacy of the drugs. In this study, iron oxide nanoparticles were prepared then surface modified via diazonium chemistry and coated with chitosan, and its derivative chitosan-grafted polylactic acid. The purpose was to increase the stability of the nanoparticles in physiological solution, heighten drug-loading capacity, prolong the release, reduce the initial burst effect and improve in vitro cytotoxicity of the model drug doxorubicin. The materials were characterized by DLS, ζ-potential, SEM, TGA, magnetization curves and release kinetics studies. Results confirmed the spherical shape, the presence of the coat and the advantages of using chitosan, particularly its amphiphilic derivative, as a coating agent, thereby surpassing the qualities of simple iron oxide nanoparticles. The coated nanoparticles exhibited great stability and high encapsulation efficiency for doxorubicin, at over 500μg per mg of carrier. Moreover, the intensity of the initial burst was clearly diminished after coating, hence represents an advantage of using the hybrid system over simple iron oxide nanoparticles. Cytotoxicity studies demonstrate the increase in cytotoxicity of doxorubicin when loaded in nanoparticles, indirectly proving the role played by the carrier and its surface properties in cell uptake. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Monocyte Trafficking, Engraftment, and Delivery of Nanoparticles and an Exogenous Gene into the Acutely Inflamed Brain Tissue - Evaluations on Monocyte-Based Delivery System for the Central Nervous System.

    Directory of Open Access Journals (Sweden)

    Hsin-I Tong

    Full Text Available The ability of monocytes and monocyte-derived macrophages (MDM to travel towards chemotactic gradient, traverse tissue barriers, and accumulate precisely at diseased sites makes them attractive candidates as drug carriers and therapeutic gene delivery vehicles targeting the brain, where treatments are often hampered by the blockade of the blood brain barrier (BBB. This study was designed to fully establish an optimized cell-based delivery system using monocytes and MDM, by evaluating their homing efficiency, engraftment potential, as well as carriage and delivery ability to transport nano-scaled particles and exogenous genes into the brain, following the non-invasive intravenous (IV cell adoptive transfer in an acute neuroinflammation mouse model induced by intracranial injection of Escherichia coli lipopolysaccharides. We demonstrated that freshly isolated monocytes had superior inflamed-brain homing ability over MDM cultured in the presence of macrophage colony stimulating factor. In addition, brain trafficking of IV infused monocytes was positively correlated with the number of adoptive transferred cells, and could be further enhanced by transient disruption of the BBB with IV administration of Mannitol, Bradykinin or Serotonin right before cell infusion. A small portion of transmigrated cells was detected to differentiate into IBA-1 positive cells with microglia morphology in the brain. Finally, with the use of superparamagnetic iron oxide nanoparticles SHP30, the ability of nanoscale agent-carriage monocytes to enter the inflamed brain region was validated. In addition, lentiviral vector DHIV-101 was used to introduce green fluorescent protein (GFP gene into monocytes, and the exogenous GFP gene was detected in the brain at 48 hours following IV infusion of the transduced monocytes. All together, our study has set up the optimized conditions for the more-in-depth tests and development of monocyte-mediated delivery, and our data supported

  19. Poly(NIPAM-co-MPS-grafted multimodal porous silica nanoparticles as reverse thermoresponsive drug delivery system

    Directory of Open Access Journals (Sweden)

    Sushilkumar A. Jadhav

    2017-05-01

    Full Text Available Hybrid drug delivery systems (DDS have been prepared by grafting poly(NIPAM-co-MPS chains on multimodal porous silica nanoparticles having an inner mesoporous structure and an outer thin layer of micropores. The hybrid thermoresponsive DDS were fully characterized and loaded with a model drug. The in vitro drug release tests are carried out at below and above the lower critical solution temperature (LCST of the copolymer. The results have revealed that due to the presence of small diameter (~1.3 nm micropores at the periphery of the particles, the collapsed globules of the thermoresponsive copolymer above its LCST hinders the complete release of the drug which resulted in a reverse thermoresponsive drug release profile by the hybrid DDS.

  20. Hydroxycamptothecin-loaded nanoparticles enhance target drug delivery and anticancer effect

    Directory of Open Access Journals (Sweden)

    Li Su

    2008-05-01

    Full Text Available Abstract Background Hydroxycamptothecin (HCPT has been shown to have activity against a broad spectrum of cancers. In order to enhance its tissue-specific delivery and anticancer activity, we prepared HCPT-loaded nanoparticles made from poly(ethylene glycol-poly(γ-benzyl-L-glutamate (PEG-PBLG, and then studied their release characteristics, pharmacokinetic characteristics, and anticancer effects. PEG-PBLG nanoparticles incorporating HCPT were prepared by a dialysis method. Scanning electron microscopy (SEM was used to observe the shape and diameter of the nanoparticles. The HCPT release characteristics in vitro were evaluated by ultraviolet spectrophotometry. A high-performance liquid chromatography (HPLC detection method for determining HCPT in rabbit plasma was established. The pharmacokinetic parameters of HCPT/PEG-PBLG nanoparticles were compared with those of HCPT. Results The HCPT-loaded nanoparticles had a core-shell spherical structure, with a core diameter of 200 nm and a shell thickness of 30 nm. Drug-loading capacity and drug encapsulation were 7.5 and 56.8%, respectively. The HCPT release profile was biphasic, with an initial abrupt release, followed by sustained release. The terminal elimination half-lives (t 1/2 β of HCPT and HCPT-loaded nanoparticles were 4.5 and 10.1 h, respectively. Peak concentrations (Cmax of HCPT and HCPT-loaded nanoparticles were 2627.8 and 1513.5 μg/L, respectively. The apparent volumes of distribution of the HCPT and HCPT-loaded nanoparticles were 7.3 and 20.0 L, respectively. Compared with a blank control group, Lovo cell xenografts or Tca8113 cell xenografts in HCPT or HCPT-loaded nanoparticle treated groups grew more slowly and the tumor doubling times were increased. The tumor inhibition effect in the HCPT-loaded nanosphere-treated group was significantly higher than that of the HCPT-treated group (p 0.05. Conclusion Compared to the HCPT- and control-treated groups, the HCPT-loaded nanoparticle

  1. Glucan Particles for Macrophage Targeted Delivery of Nanoparticles

    Directory of Open Access Journals (Sweden)

    Ernesto R. Soto

    2012-01-01

    Full Text Available Glucan particles (GPs are hollow, porous 2–4 μm microspheres derived from the cell walls of Baker's yeast (Saccharomyces cerevisiae. The 1,3-β-glucan outer shell provides for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors. GPs have been used for macrophage-targeted delivery of soluble payloads (DNA, siRNA, protein, and small molecules encapsulated inside the hollow GPs via core polyplex and layer-by-layer (LbL synthetic strategies. In this communication, we report the incorporation of nanoparticles as cores inside GPs (GP-NP or electrostatically bound to the surface of chemically derivatized GPs (NP-GP. GP nanoparticle formulations benefit from the drug encapsulation properties of NPs and the macrophage-targeting properties of GPs. GP nanoparticle formulations were synthesized using fluorescent anionic polystyrene nanoparticles allowing visualization and quantitation of NP binding and encapsulation. Mesoporous silica nanoparticles (MSNs containing the chemotherapeutic doxorubicin (Dox were bound to cationic GPs. Dox-MSN-GPs efficiently delivered Dox into GP phagocytic cells resulting in enhanced Dox-mediated growth arrest.

  2. Recent advances in protein and Peptide drug delivery: a special emphasis on polymeric nanoparticles.

    Science.gov (United States)

    Patel, Ashaben; Patel, Mitesh; Yang, Xiaoyan; Mitra, Ashim K

    2014-01-01

    Proteins and peptides are widely indicated in many diseased states. Parenteral route is the most commonly em- ployed method of administration for therapeutic proteins and peptides. However, requirement of frequent injections due to short in vivo half-life results in poor patient compliance. Non-invasive drug delivery routes such as nasal, transdermal, pulmonary, and oral offer several advantages over parenteral administration. Intrinsic physicochemical properties and low permeability across biological membrane limit protein delivery via non-invasive routes. One of the strategies to improve protein and peptide absorption is by delivering through nanostructured delivery carriers. Among nanocarriers, polymeric nanoparticles (NPs) have demonstrated significant advantages over other delivery systems. This article summarizes the application of polymeric NPs for protein and peptide drug delivery following oral, nasal, pulmonary, parenteral, transder mal, and ocular administrations.

  3. Efficient systemic DNA delivery to the tumor by self-assembled nanoparticle

    Science.gov (United States)

    Tang, Hailin; Xie, Xinhua; Guo, Jiaoli; Wei, Weidong; Wu, Minqing; Liu, Peng; Kong, Yanan; Yang, Lu; Hung, Mien-Chie; Xie, Xiaoming

    2014-01-01

    There are few delivery agents that could deliver gene with high efficiency and low toxicity, especially for animal experiments. Therefore, creating vectors with good delivery efficiency and safety profile is a meaningful work. We have developed a self-assembled gene delivery system (XM001), which can more efficiently deliver DNA to multiple cell lines and breast tumor, as compared to commercial delivery agents. In addition, systemically administrated XM001-BikDD (BikDD is a mutant form of proapoptotic gene Bik) significantly inhibited the growth of human breast cancer cells and prolonged the life span in implanted nude mice. This study demonstrates that XM001 is an efficient and widespread transfection agent, which could be a promising tumor delivery vector for cancer targeted therapy.

  4. Delivery Systems for Birch-Bark Triterpenoids and Their Derivatives in Anticancer Research.

    Science.gov (United States)

    Mierina, Inese; Vilskersts, Reinis; Turks, Maris

    2018-05-29

    Birch-bark triterpenoids and their semi-synthetic derivatives possess a wide range of biological activities including cytotoxic effects on various tumour cell lines. However, due to the low solubility and bioavailability, their medicinal applications are rather limited. The use of various nanotechnology-based drug delivery systems is rapidly developing approach to the solubilisation of insufficiently bioavailable pharmaceuticals. Herein, the drug delivery systems deemed to be applicable for birch-bark triterpenoid structures are reviewed. The aforementioned disadvantages of birch-bark triterpenoids and their semi-synthetic derivatives can be overcome through their incorporation into organic nanoparticles, which include various dendrimeric systems, as well as embedding the active compounds into polymer matrices or complexation with carbohydrate nanoparticles without covalent bonding. Some of the known triterpenoid delivery systems consist of nanoparticles featuring inorganic cores covered with carbohydrates or other polymers. Methods for delivering the title compounds through encapsulation and emulsification into lipophilic media are also suitable. Besides, the birch-bark triterpenoids can form self-assembling systems with increased bio-availability. Even more, the self-assembling systems are used as carriers for delivering other chemotherapeutic agents. Another advantage besides increased bioavailability and anticancer activity is the reduced overall systemic toxicity in most of the cases, when triterpenoids are delivered with any of the carriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Lipid-polymer hybrid nanoparticles: Development & statistical optimization of norfloxacin for topical drug delivery system

    Directory of Open Access Journals (Sweden)

    Vivek Dave

    2017-12-01

    Full Text Available Poly lactic acid is a biodegradable, biocompatible, and non-toxic polymer, widely used in many pharmaceutical preparations such as controlled release formulations, parenteral preparations, surgical treatment applications, and tissue engineering. In this study, we prepared lipid-polymer hybrid nanoparticles for topical and site targeting delivery of Norfloxacin by emulsification solvent evaporation method (ESE. The design of experiment (DOE was done by using software to optimize the result, and then a surface plot was generated to compare with the practical results. The surface morphology, particle size, zeta potential and composition of the lipid-polymer hybrid nanoparticles were characterized by SEM, TEM, AFM, and FTIR. The thermal behavior of the lipid-polymer hybrid nanoparticles was characterized by DSC and TGA. The prepared lipid-polymer hybrid nanoparticles of Norfloxacin exhibited an average particle size from 178.6 ± 3.7 nm to 220.8 ± 2.3 nm, and showed very narrow distribution with polydispersity index ranging from 0.206 ± 0.36 to 0.383 ± 0.66. The surface charge on the lipid-polymer hybrid nanoparticles were confirmed by zeta potential, showed the value from +23.4 ± 1.5 mV to +41.5 ± 3.4 mV. An Antimicrobial study was done against Staphylococcus aureus and Pseudomonas aeruginosa, and the lipid-polymer hybrid nanoparticles showed potential activity against these two. Lipid-polymer hybrid nanoparticles of Norfloxacin showed the %cumulative drug release of 89.72% in 24 h. A stability study of the optimized formulation showed the suitable condition for the storage of lipid-polymer hybrid nanoparticles was at 4 ± 2 °C/60 ± 5% RH. These results illustrated high potential of lipid-polymer hybrid nanoparticles Norfloxacin for usage as a topical antibiotic drug carriers.

  6. Nanotechnology-based drug delivery systems for control of microbial biofilms: a review.

    Science.gov (United States)

    Dos Santos Ramos, Matheus Aparecido; Da Silva, Patrícia Bento; Spósito, Larissa; De Toledo, Luciani Gaspar; Bonifácio, Bruna Vidal; Rodero, Camila Fernanda; Dos Santos, Karen Cristina; Chorilli, Marlus; Bauab, Taís Maria

    2018-01-01

    Since the dawn of civilization, it has been understood that pathogenic microorganisms cause infectious conditions in humans, which at times, may prove fatal. Among the different virulent properties of microorganisms is their ability to form biofilms, which has been directly related to the development of chronic infections with increased disease severity. A problem in the elimination of such complex structures (biofilms) is resistance to the drugs that are currently used in clinical practice, and therefore, it becomes imperative to search for new compounds that have anti-biofilm activity. In this context, nanotechnology provides secure platforms for targeted delivery of drugs to treat numerous microbial infections that are caused by biofilms. Among the many applications of such nanotechnology-based drug delivery systems is their ability to enhance the bioactive potential of therapeutic agents. The present study reports the use of important nanoparticles, such as liposomes, microemulsions, cyclodextrins, solid lipid nanoparticles, polymeric nanoparticles, and metallic nanoparticles, in controlling microbial biofilms by targeted drug delivery. Such utilization of these nanosystems has led to a better understanding of their applications and their role in combating biofilms.

  7. Insulin-loaded poly(epsilon-caprolactone) nanoparticles: efficient, sustained and safe insulin delivery system.

    Science.gov (United States)

    de Araújo, Thiago M; Teixeira, Zaine; Barbosa-Sampaio, Helena C; Rezende, Luiz F; Boschero, Antonio C; Durán, Nelson; Höehr, Nelci F

    2013-06-01

    The aim of this work was to develop an efficient, biodegradable, biocompatible and safe controlled release system using insulin-loaded poly(epsilon-caprolactone) (PCL) nanoparticles. The insulin-loaded PCL nanoparticles were prepared by double emulsion method (water-in-oil-in-water) using Pluronic F68 as emulsifier. Using the double emulsion method a high insulin encapsulation efficiency (90.6 +/-1.6%) with a zeta potential of -29 +/-2.7 mV and average particle size of 796 +/-10.5 nm was obtained. Insulin-loaded PCL nanoparticles showed no toxicity to MIN6 cells. Insulin nanoparticles administered subcutaneously and intraperitoneally in rats reduced glycaemia of basal levels after 15 minutes, and presented a sustainable hypoglycemic effect on insulin-dependent type 1 diabetic rats, showing to be more efficient than unencapsulated insulin. Furthermore, these nanoparticles were not hepatotoxic, as evaluated by the effect over liver cell-death and oxidative stress scavenger system in rats. These results suggest that insulin-loaded PCL nanoparticles prepared by water-in-oil-in-water emulsion method are biocompatible, efficient and safe insulin-delivering system with controlled insulin release, which indicates that it may be a powerful tool for insulin-dependent patients care.

  8. Fabrication of silk fibroin nanoparticles for controlled drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Zhao Zheng; Chen Aizheng; Li Yi, E-mail: tcliyi@polyu.edu.hk; Hu Junyan; Liu Xuan; Li Jiashen; Zhang Yu; Li Gang; Zheng Zijian [Hong Kong Polytechnic University, Institute of Textiles and Clothing (Hong Kong)

    2012-03-15

    A novel solution-enhanced dispersion by supercritical CO{sub 2} (SEDS) was employed to prepare silk fibroin (SF) nanoparticles. The resulting SF nanoparticles exhibited a good spherical shape, a smooth surface, and a narrow particle size distribution with a mean particle diameter of about 50 nm. The results of X-ray powder diffraction, thermo gravimetry-differential scanning calorimetry, and Fourier transform infrared spectroscopy analysis of the SF nanoparticles before and after ethanol treatment indicated conformation transition of SF nanoparticles from random coil to {beta}-sheet form and thus water insolubility. The MTS assay also suggested that the SF nanoparticles after ethanol treatment imposed no toxicity. A non-steroidal anti-inflammatory drug, indomethacin (IDMC), was chosen as the model drug and was encapsulated in SF nanoparticles by the SEDS process. The resulting IDMC-SF nanoparticles, after ethanol treatment, possessed a theoretical average drug load of 20%, an actual drug load of 2.05%, and an encapsulation efficiency of 10.23%. In vitro IDMC release from the IDMC-SF nanoparticles after ethanol treatment showed a significantly sustained release over 2 days. These studies of SF nanoparticles indicated the suitability of the SF nanoparticles prepared by the SEDS process as a biocompatible carrier to deliver drugs and also the feasibility of using the SEDS process to reach the goal of co-precipitation of drug and SF as composite nanoparticles for controlled drug delivery.

  9. Fabrication of silk fibroin nanoparticles for controlled drug delivery

    International Nuclear Information System (INIS)

    Zhao Zheng; Chen Aizheng; Li Yi; Hu Junyan; Liu Xuan; Li Jiashen; Zhang Yu; Li Gang; Zheng Zijian

    2012-01-01

    A novel solution-enhanced dispersion by supercritical CO 2 (SEDS) was employed to prepare silk fibroin (SF) nanoparticles. The resulting SF nanoparticles exhibited a good spherical shape, a smooth surface, and a narrow particle size distribution with a mean particle diameter of about 50 nm. The results of X-ray powder diffraction, thermo gravimetry-differential scanning calorimetry, and Fourier transform infrared spectroscopy analysis of the SF nanoparticles before and after ethanol treatment indicated conformation transition of SF nanoparticles from random coil to β-sheet form and thus water insolubility. The MTS assay also suggested that the SF nanoparticles after ethanol treatment imposed no toxicity. A non-steroidal anti-inflammatory drug, indomethacin (IDMC), was chosen as the model drug and was encapsulated in SF nanoparticles by the SEDS process. The resulting IDMC–SF nanoparticles, after ethanol treatment, possessed a theoretical average drug load of 20%, an actual drug load of 2.05%, and an encapsulation efficiency of 10.23%. In vitro IDMC release from the IDMC–SF nanoparticles after ethanol treatment showed a significantly sustained release over 2 days. These studies of SF nanoparticles indicated the suitability of the SF nanoparticles prepared by the SEDS process as a biocompatible carrier to deliver drugs and also the feasibility of using the SEDS process to reach the goal of co-precipitation of drug and SF as composite nanoparticles for controlled drug delivery.

  10. Comparative study of chitosan- and PEG-coated lipid and PLGA nanoparticles as oral delivery systems for cannabinoids

    International Nuclear Information System (INIS)

    Durán-Lobato, Matilde; Martín-Banderas, Lucía; Gonçalves, Lídia M. D.; Fernández-Arévalo, Mercedes; Almeida, Antonio J.

    2015-01-01

    The cannabinoid derivative 1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone (CB13) has an important therapeutic potential as analgesic in chronic pain states that respond poorly to conventional drugs. However, the incidence of its mild-to-moderate and dose-dependent adverse effects, as well as its pharmacokinetic profile, actually holds back its use in humans. Thus, the use of a suitable carrier system for oral delivery of CB13 becomes an attractive strategy to develop a valuable therapy. Polymeric poly(lactic-co-glycolic) acid (PLGA) and lipid nanoparticles (LNPs) are widely studied delivery vehicles that improve the bioavailability of lipophilic compounds and present special interest in oral delivery. Their surface can be modified to improve the adhesion of particles to the oral mucosa and increase their circulation time in blood with additives such as chitosan (CS) and polyethylene glycol (PEG), which can be feasibly incorporated onto these particles in a post-production step. In this work, CS- and PEG-modified polymeric PLGA and LNPs were successfully obtained and comparatively evaluated under the same experimental conditions as oral carriers for CB13. All the formulations presented adequate blood compatibility and absence of cytotoxicity in Caco-2 cells. Coating with CS led to a higher interaction with Caco-2 cells and a limited uptake in THP1 cells, while coating with PEG led to a limited uptake in Caco-2 cells and strongly prevented THP1 cells uptake. The performance of each formulation is discussed as a comparison of the potential of these carriers as oral delivery systems of CB13

  11. Comparative study of chitosan- and PEG-coated lipid and PLGA nanoparticles as oral delivery systems for cannabinoids

    Science.gov (United States)

    Durán-Lobato, Matilde; Martín-Banderas, Lucía; Gonçalves, Lídia M. D.; Fernández-Arévalo, Mercedes; Almeida, Antonio J.

    2015-02-01

    The cannabinoid derivative 1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone (CB13) has an important therapeutic potential as analgesic in chronic pain states that respond poorly to conventional drugs. However, the incidence of its mild-to-moderate and dose-dependent adverse effects, as well as its pharmacokinetic profile, actually holds back its use in humans. Thus, the use of a suitable carrier system for oral delivery of CB13 becomes an attractive strategy to develop a valuable therapy. Polymeric poly(lactic-co-glycolic) acid (PLGA) and lipid nanoparticles (LNPs) are widely studied delivery vehicles that improve the bioavailability of lipophilic compounds and present special interest in oral delivery. Their surface can be modified to improve the adhesion of particles to the oral mucosa and increase their circulation time in blood with additives such as chitosan (CS) and polyethylene glycol (PEG), which can be feasibly incorporated onto these particles in a post-production step. In this work, CS- and PEG-modified polymeric PLGA and LNPs were successfully obtained and comparatively evaluated under the same experimental conditions as oral carriers for CB13. All the formulations presented adequate blood compatibility and absence of cytotoxicity in Caco-2 cells. Coating with CS led to a higher interaction with Caco-2 cells and a limited uptake in THP1 cells, while coating with PEG led to a limited uptake in Caco-2 cells and strongly prevented THP1 cells uptake. The performance of each formulation is discussed as a comparison of the potential of these carriers as oral delivery systems of CB13.

  12. Comparative study of chitosan- and PEG-coated lipid and PLGA nanoparticles as oral delivery systems for cannabinoids

    Energy Technology Data Exchange (ETDEWEB)

    Durán-Lobato, Matilde; Martín-Banderas, Lucía, E-mail: luciamartin@us.es [Universidad de Sevilla, Departmento Farmacia y Tecnología Farmacéutica, Facultad de Farmacia (España) (Spain); Gonçalves, Lídia M. D. [Universidade de Lisboa, Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculdade de Farmácia (Portugal); Fernández-Arévalo, Mercedes [Universidad de Sevilla, Departmento Farmacia y Tecnología Farmacéutica, Facultad de Farmacia (España) (Spain); Almeida, Antonio J. [Universidade de Lisboa, Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculdade de Farmácia (Portugal)

    2015-02-15

    The cannabinoid derivative 1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone (CB13) has an important therapeutic potential as analgesic in chronic pain states that respond poorly to conventional drugs. However, the incidence of its mild-to-moderate and dose-dependent adverse effects, as well as its pharmacokinetic profile, actually holds back its use in humans. Thus, the use of a suitable carrier system for oral delivery of CB13 becomes an attractive strategy to develop a valuable therapy. Polymeric poly(lactic-co-glycolic) acid (PLGA) and lipid nanoparticles (LNPs) are widely studied delivery vehicles that improve the bioavailability of lipophilic compounds and present special interest in oral delivery. Their surface can be modified to improve the adhesion of particles to the oral mucosa and increase their circulation time in blood with additives such as chitosan (CS) and polyethylene glycol (PEG), which can be feasibly incorporated onto these particles in a post-production step. In this work, CS- and PEG-modified polymeric PLGA and LNPs were successfully obtained and comparatively evaluated under the same experimental conditions as oral carriers for CB13. All the formulations presented adequate blood compatibility and absence of cytotoxicity in Caco-2 cells. Coating with CS led to a higher interaction with Caco-2 cells and a limited uptake in THP1 cells, while coating with PEG led to a limited uptake in Caco-2 cells and strongly prevented THP1 cells uptake. The performance of each formulation is discussed as a comparison of the potential of these carriers as oral delivery systems of CB13.

  13. Bioinspired silica as drug delivery systems and their biocompatibility

    DEFF Research Database (Denmark)

    Steven, Christopher R.; Busby, Grahame A.; Mather, Craig

    2014-01-01

    Silica nanoparticles have been shown to have great potential as drug delivery systems (DDS), however, their fabrication often involves harsh chemicals and energy intensive laborious methods. This work details the employment of a bioinspired "green" method for the controlled synthesis of silica, use...

  14. Doxorubicin loaded PEG-b-poly(4-vinylbenzylphosphonate) coated magnetic iron oxide nanoparticles for targeted drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Hałupka-Bryl, Magdalena, E-mail: magdalenahalupka@op.pl [The NanoBioMedical Centre, Adam Mickiewicz University, Poznań (Poland); Division of Medical Physics, Faculty of Physics, Adam Mickiewicz University, Poznań (Poland); Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba (Japan); Bednarowicz, Magdalena [The NanoBioMedical Centre, Adam Mickiewicz University, Poznań (Poland); Division of Medical Physics, Faculty of Physics, Adam Mickiewicz University, Poznań (Poland); Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba (Japan); Dobosz, Bernadeta; Krzyminiewski, Ryszard [The NanoBioMedical Centre, Adam Mickiewicz University, Poznań (Poland); Division of Medical Physics, Faculty of Physics, Adam Mickiewicz University, Poznań (Poland); Zalewski, Tomasz [The NanoBioMedical Centre, Adam Mickiewicz University, Poznań (Poland); Wereszczyńska, Beata [Department of Macromolecular Physics, Adam Mickiewicz University, Poznań (Poland); Nowaczyk, Grzegorz; Jarek, Marcin [The NanoBioMedical Centre, Adam Mickiewicz University, Poznań (Poland); Nagasaki, Yukio [Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba (Japan); Master’s School of Medicinal Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba (Japan); International Centre for Materials Nanoarchitectonics Satellite (WPI-MANA), National Institute For Materials Sciences (NIMS) and University of Tsukuba (Japan)

    2015-06-15

    Due to their unique physical properties, superparamagnetic iron oxide nanoparticles are increasingly used in medical applications. They are very useful carriers for delivering antitumor drugs in targeted cancer treatment. Magnetic nanoparticles with chemiotherapeutic were synthesized by coprecipitation method followed by coating with biocompatible polymer. The aim of this work is to characterize physical and magnetic properties of synthesized nanoparicles. Characterization was carried out using EPR, HRTEM, X-ray diffraction, SQUID and NMR methods. The present findings show that synthesized nanosystem is promising tool for potential magnetic drug delivery. - Highlights: • Synthesized PEG-PIONs/DOX have excellent physical properties. • PEG-PIONs/DOX have a potential to in vivo application. • PEG-PIONs/DOX could be used as drug delivery system as well as contrast agents.

  15. Nanoparticles in Porous Microparticles Prepared by Supercritical Infusion and Pressure Quench Technology for Sustained Delivery of Bevacizumab

    Science.gov (United States)

    K.Yandrapu, Sarath; Upadhyay, Arun K.; Petrash, J. Mark; Kompella, Uday B.

    2014-01-01

    Nanoparticles in porous microparticles (NPinPMP), a novel delivery system for sustained delivery of protein drugs, was developed using supercritical infusion and pressure quench technology, which does not expose proteins to organic solvents or sonication. The delivery system design is based on the ability of supercritical carbon dioxide (SC CO2) to expand poly(lactic-co-glycolic) acid (PLGA) matrix but not polylactic acid (PLA) matrix. The technology was applied to bevacizumab, a protein drug administered once a month intravitreally to treat wet age related macular degeneration. Bevacizumab coated PLA nanoparticles were encapsulated into porosifying PLGA microparticles by exposing the mixture to SC CO2. After SC CO2 exposure, the size of PLGA microparticles increased by 6.9 fold. Confocal and scanning electron microscopy studies demonstrated the expansion and porosification of PLGA microparticles and infusion of PLA nanoparticles inside PLGA microparticles. In vitro release of bevacizumab from NPinPMP was sustained for 4 months. Size exclusion chromatography, fluorescence spectroscopy, circular dichroism spectroscopy, SDS-PAGE, and ELISA studies indicated that the released bevacizumab maintained its monomeric form, conformation, and activity. Further, in vivo delivery of bevacizumab from NPinPMP was evaluated using noninvasive fluorophotometry after intravitreal administration of Alexa Flour 488 conjugated bevacizumab in either solution or NPinPMP in a rat model. Unlike the vitreal signal from Alexa-bevacizumab solution, which reached baseline at 2 weeks, release of Alexa-bevacizumab from NPinPMP could be detected for 2 months. Thus, NPinPMP is a novel sustained release system for protein drugs to reduce frequency of protein injections in the therapy of back of the eye diseases. PMID:24131101

  16. Nanoparticles in porous microparticles prepared by supercritical infusion and pressure quench technology for sustained delivery of bevacizumab.

    Science.gov (United States)

    Yandrapu, Sarath K; Upadhyay, Arun K; Petrash, J Mark; Kompella, Uday B

    2013-12-02

    Nanoparticles in porous microparticles (NPinPMP), a novel delivery system for sustained delivery of protein drugs, was developed using supercritical infusion and pressure quench technology, which does not expose proteins to organic solvents or sonication. The delivery system design is based on the ability of supercritical carbon dioxide (SC CO2) to expand poly(lactic-co-glycolic) acid (PLGA) matrix but not polylactic acid (PLA) matrix. The technology was applied to bevacizumab, a protein drug administered once a month intravitreally to treat wet age related macular degeneration. Bevacizumab coated PLA nanoparticles were encapsulated into porosifying PLGA microparticles by exposing the mixture to SC CO2. After SC CO2 exposure, the size of PLGA microparticles increased by 6.9-fold. Confocal and scanning electron microscopy studies demonstrated the expansion and porosification of PLGA microparticles and infusion of PLA nanoparticles inside PLGA microparticles. In vitro release of bevacizumab from NPinPMP was sustained for 4 months. Size exclusion chromatography, fluorescence spectroscopy, circular dichroism spectroscopy, SDS-PAGE, and ELISA studies indicated that the released bevacizumab maintained its monomeric form, conformation, and activity. Further, in vivo delivery of bevacizumab from NPinPMP was evaluated using noninvasive fluorophotometry after intravitreal administration of Alexa Fluor 488 conjugated bevacizumab in either solution or NPinPMP in a rat model. Unlike the vitreal signal from Alexa-bevacizumab solution, which reached baseline at 2 weeks, release of Alexa-bevacizumab from NPinPMP could be detected for 2 months. Thus, NPinPMP is a novel sustained release system for protein drugs to reduce frequency of protein injections in the therapy of back of the eye diseases.

  17. Biofunctionalized nanoparticles with pH-responsive and cell penetrating blocks for gene delivery

    International Nuclear Information System (INIS)

    Gaspar, V M; Marques, J G; Sousa, F; Queiroz, J A; Correia, I J; Louro, R O

    2013-01-01

    Bridging the gap between nanoparticulate delivery systems and translational gene therapy is a long sought after requirement in nanomedicine-based applications. However, recent developments regarding nanoparticle functionalization have brought forward the ability to synthesize materials with biofunctional moieties that mimic the evolved features of viral particles. Herein we report the versatile conjugation of both cell penetrating arginine and pH-responsive histidine moieties into the chitosan polymeric backbone, to improve the physicochemical characteristics of the native material. Amino acid coupling was confirmed by 2D TOCSY NMR and Fourier transform infrared spectroscopy. The synthesized chitosan–histidine–arginine (CH–H–R) polymer complexed plasmid DNA biopharmaceuticals, and spontaneously assembled into stable 105 nm nanoparticles with spherical morphology and positive surface charge. The functionalized delivery systems were efficiently internalized into the intracellular compartment, and exhibited remarkably higher transfection efficiency than unmodified chitosan without causing any cytotoxic effect. Additional findings regarding intracellular trafficking events reveal their preferential escape from degradative lysosomal pathways and nuclear localization. Overall, this assembly of nanocarriers with bioinspired moieties provides the foundations for the design of efficient and customizable materials for cancer gene therapy. (paper)

  18. Comparison of different cationized proteins as biomaterials for nanoparticle-based ocular gene delivery.

    Science.gov (United States)

    Zorzi, Giovanni K; Párraga, Jenny E; Seijo, Begoña; Sanchez, Alejandro

    2015-11-01

    Cationized polymers have been proposed as transfection agents for gene therapy. The present work aims to improve the understanding of the potential use of different cationized proteins (atelocollagen, albumin and gelatin) as nanoparticle components and to investigate the possibility of modulating the physicochemical properties of the resulting nanoparticle carriers by selecting specific protein characteristics in an attempt to improve current ocular gene-delivery approaches. The toxicity profiles, as well as internalization and transfection efficiency, of the developed nanoparticles can be modulated by modifying the molecular weight of the selected protein and the amine used for cationization. The most promising systems are nanoparticles based on intermediate molecular weight gelatin cationized with the endogenous amine spermine, which exhibit an adequate toxicological profile, as well as effective association and protection of pDNA or siRNA molecules, thereby resulting in higher transfection efficiency and gene silencing than the other studied formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Synthesis, Characterization, and In Vitro Drug Delivery Capabilities of (Zn, Al-Based Layered Double Hydroxide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Vinay J. Nagaraj

    2015-01-01

    Full Text Available There is an urgent need for the development of alternative strategies for effective drug delivery to improve the outcome of patients suffering from deadly diseases such as cancer. Nanoparticles, in particular layered double hydroxide (LDH nanoparticles, have great potential as nanocarriers of chemotherapeutic molecules. In this study, we synthesized (Zn, Al-LDH nanoparticles and report their enhanced pH-dependent stability in comparison to the commonly used (Mg, Al-LDH nanoparticles. Fluorescein isothiocyanate (FITC and valproate (VP were intercalated into (Zn, Al-LDH nanoparticles to study cellular uptake, biocompatibility, and drug delivery capabilities using cultured pancreatic adenocarcinoma BxPC3 cells. Fluorescence measurements indicated that FITC-intercalated LDH nanoparticles showed a greater degree of energy-dependent uptake rather than passive uptake by BxPC3 cells, especially at high concentrations of nanoparticles. Tetrazolium-based colorimetric assays indicated that BxPC3 cells treated with VP-intercalated LDH nanoparticles showed a significant reduction in cell viability along with about 30-fold reduction in IC50 compared to the drug alone. In contrast, the non-drug-intercalated LDH nanoparticles did not affect the cell viability indicating very low innate cytotoxicity. Our research indicates that the superior properties of (Zn, Al-LDH nanoparticles make them ideal candidates for further development as in vivo chemotherapy drug delivery agents.

  20. Development and characterization of a new carrier for vaccine delivery based on calcium-alginate nanoparticles: Safe immunoprotective approach against scorpion envenoming.

    Science.gov (United States)

    Nait Mohamed, Faez Amokrane; Laraba-Djebari, Fatima

    2016-05-23

    To enhance humoral defense against diseases, vaccine formulation is routinely prepared to improve immune response. Studies in nanomaterials as a carrier of vaccine delivery are promising and interesting. In this study, attenuated Androctonus australis hector (Aah) venom and its toxic fraction were encapsulated into different formulations inside calcium-alginate nanoparticles (Ca-Alg Nps), and used as a vaccine delivery system against scorpion envenomation. Ca-Alg Nps were prepared by ionic gelation and characterized. An immunization schedule was undertaken in rabbits in order to study how Aah venom entrapped in Ca-Alg Nps might induce protective immunity. Results showed the influence of different parameters on the suitable nanoparticle formation. They also showed no toxicity of free Ca-Alg Nps and a different inflammatory profile depending on the nanovaccine formulations. More interestingly, evaluation of specific IgG titer and IgG1/IgG2a isotype balance revealed a protective effect with the nanoparticles encapsulating the attenuated antigens. Challenge up to 6 LD 50 of native venom, allowed to an important immunoprotection of all immunized rabbits, with no recorded death. Taken together and with respect to the properties of nanoparticles and high immunogenicity, calcium-alginate nanoparticles could be considered as a new promising adjuvant system and a vaccine delivery against scorpion envenomation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Chitosan-coated poly(lactic-co-glycolic acid nanoparticles as an efficient delivery system for Newcastle disease virus DNA vaccine

    Directory of Open Access Journals (Sweden)

    Zhao K

    2014-09-01

    Full Text Available Kai Zhao,1,* Yang Zhang,1,2,* Xiaoyan Zhang,1,* Ci Shi,1,2 Xin Wang,1 Xiaohua Wang,1 Zheng Jin,3 Shangjin Cui2 1Laboratory of Microbiology, School of Life Science, Heilongjiang University, 2Division of Swine Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, 3Key Laboratory of Chemical Engineering Process and Technology for High-efficiency Conversion, Heilongjiang University, Harbin, People’s Republic of China *These authors contributed equally to this work Abstract: We determined the efficacy and safety of chitosan (CS-coated poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs as a delivery system for a vaccine to protect chickens against Newcastle disease virus (NDV. The newly constructed vaccine contained DNA (the F gene of NDV. The Newcastle disease virus (NDV F gene deoxyribonucleic acid (DNA plasmid (pFDNA-CS/PLGA-NPs were spherical (diameter =699.1±5.21 nm [mean ± ­standard deviation] and smooth, with an encapsulation efficiency of 98.1% and a Zeta potential of +6.35 mV. An in vitro release assay indicated that CS controlled the burst release of plasmid DNA, such that up to 67.4% of the entire quantity of plasmid DNA was steadily released from the pFDNA-CS/PLGA-NPs. An in vitro expression assay indicated that the expression of nanoparticles (NPs was maintained in the NPs. In an immunization test with specific pathogen-free chickens, the pFDNA-CS/PLGA-NPs induced stronger cellular, humoral, and mucosal immune responses than the plasmid DNA vaccine alone. The pFDNA-CS/PLGA-NPs did not harm 293T cells in an in vitro assay and did not harm chickens in an in vivo assay. Overall, the results indicated that CS-coated PLGA NPs can serve as an efficient and safe mucosal immune delivery system for NDV DNA vaccine.Keywords: mucosal immune delivery system, immune effect

  2. Hydrophobically modified chitosan/gold nanoparticles for DNA delivery

    International Nuclear Information System (INIS)

    Bhattarai, Shanta Raj; Remant Bahadur, K.C.; Aryal, Santosh; Bhattarai, Narayan; Kim, Sun Young; Yi, Ho Keun; Hwang, Pyoung Han; Kim, Hak Yong

    2008-01-01

    Present study dealt an application of modified chitosan gold nanoparticles (Nac-6-Au) for the immobilization of necked plasmid DNA. Gold nanoparticles stabilized with N-acylated chitosan were prepared by graft-onto approach. The stabilized gold nanoparticles were characterized by different physico-chemical techniques such as UV-vis, TEM, ELS and DLS. MTT assay was used for in vitro cytotoxicity of the nanoparticles into three different cell lines (NIH 3T3, CT-26 and MCF-7). The formulation of plasmid DNA with the nanoparticles corresponds to the complex forming capacity and in-vitro/in-vivo transfection efficiency was studied via gel electrophoresis and transfection methods, respectively. Results showed the modified chitosan gold nanoparticles were well-dispersed and spherical in shape with average size around 10∼12 nm in triple distilled water at pH 7.4, and showed relatively no cytotoxicity at low concentration. Addition of plasmid DNA on the aqueous solution of the nanoparticles markedly reduced surface potential (50.0∼66.6%) as well as resulted in a 13.33% increase in hydrodynamic diameters of the formulated nanoparticles. Transfection efficiency of Nac-6-Au/DNA was dependent on cell type, and higher β-galactosidase activity was observed on MCF-7 breast cancer cell. Typically, this activity was 5 times higher in 4.5 mg/ml nanoparticles concentration than that achieved by the nanoparticles of other concentrations (and/or control). However, this activity was lower in in-vitro and dramatically higher in in-vivo than that of commercially available transfection kit (Lipofectin (registered) ) and DNA. From these results, it can be expected to develop alternative new vectors for gene delivery

  3. Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system

    Directory of Open Access Journals (Sweden)

    Gomes MJ

    2014-04-01

    Full Text Available Maria João Gomes,1 José das Neves,1,2 Bruno Sarmento1,2 1Instituto de Engenharia Biomédica (INEB, Porto, Portugal; 2Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (IINFACTS, Instituto Superior de Ciências da Saúde-Norte, CESPU, Gandra, Portugal Abstract: Antiretroviral drug therapy plays a cornerstone role in the treatment of human immunodeficiency virus (HIV/acquired immunodeficiency syndrome patients. Despite obvious advances over the past 3 decades, new approaches toward improved management of infected individuals are still required. Drug distribution to the central nervous system (CNS is required in order to limit and control viral infection, but the presence of natural barrier structures, in particular the blood–brain barrier, strongly limits the perfusion of anti-HIV compounds into this anatomical site. Nanotechnology-based approaches may help providing solutions for antiretroviral drug delivery to the CNS by potentially prolonging systemic drug circulation, increasing the crossing and reducing the efflux of active compounds at the blood–brain barrier, and providing cell/tissue-targeting and intracellular drug delivery. After an initial overview on the basic features of HIV infection of the CNS and barriers to active compound delivery to this anatomical site, this review focuses on recent strategies based on antiretroviral drug-loaded solid nanoparticles and drug nanosuspensions for the potential management of HIV infection of the CNS. Keywords: HIV/AIDS, blood–brain barrier, protease inhibitors, efflux transporters, drug targeting

  4. BDNF gene delivery mediated by neuron-targeted nanoparticles is neuroprotective in peripheral nerve injury

    OpenAIRE

    Lopes, CDF; Gonçalves, NP; Gomes, CP; Saraiva, MJ; Pêgo, AP

    2017-01-01

    Neuron-targeted gene delivery is a promising strategy to treat peripheral neuropathies. Here we propose the use of polymeric nanoparticles based on thiolated trimethyl chitosan (TMCSH) to mediate targeted gene delivery to peripheral neurons upon a peripheral and minimally invasive intramuscular administration. Nanoparticles were grafted with the non-toxic carboxylic fragment of the tetanus neurotoxin (HC) to allow neuron targeting and were explored to deliver a plasmid DNA encoding for the br...

  5. In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine-based nanoparticles

    Directory of Open Access Journals (Sweden)

    Lopes CDF

    2016-06-01

    Full Text Available Cátia DF Lopes,1–3,* Hugo Oliveira,1,* Inês Estevão,1 Liliana Raquel Pires,1 Ana Paula Pêgo1,2,4,5 1INEB – Instituto de Engenharia Biomédica, Universidade do Porto (UPorto, Porto, Portugal; 2i3S – Instituto de Investigação e Inovação em Saúde, NanoBiomaterials for Targeted Therapies Group, UPorto, Porto, Portugal; 3FMUP – Faculdade de Medicina da Universidade do Porto, Porto, Portugal; 4ICBAS – Instituto de Ciências Biomédicas Abel Salazar, UPorto, Porto, Portugal; 5FEUP – Faculdade de Engenharia da Universidade do Porto, Porto, Portugal *These authors contributed equally to this work Abstract: A major challenge in neuronal gene therapy is to achieve safe, efficient, and minimally invasive transgene delivery to neurons. In this study, we report the use of a nonviral neurotropic poly(ethylene imine-based nanoparticle that is capable of mediating neuron-specific transfection upon a subcutaneous injection. Nanoparticles were targeted to peripheral neurons by using the nontoxic carboxylic fragment of tetanus toxin (HC, which, besides being neurotropic, is capable of being retrogradely transported from neuron terminals to the cell bodies. Nontargeted particles and naked plasmid DNA were used as control. Five days after treatment by subcutaneous injection in the footpad of Wistar rats, it was observed that 56% and 64% of L4 and L5 dorsal root ganglia neurons, respectively, were expressing the reporter protein. The delivery mediated by HC-functionalized nanoparticles spatially limited the transgene expression, in comparison with the controls. Histological examination revealed no significant adverse effects in the use of the proposed delivery system. These findings demonstrate the feasibility and safety of the developed neurotropic nanoparticles for the minimally invasive delivery of genes to the peripheral nervous system, opening new avenues for the application of gene therapy strategies in the treatment of peripheral

  6. Paclitaxel molecularly imprinted polymer-PEG-folate nanoparticles for targeting anticancer delivery: Characterization and cellular cytotoxicity

    International Nuclear Information System (INIS)

    Esfandyari-Manesh, Mehdi; Darvishi, Behrad; Ishkuh, Fatemeh Azizi; Shahmoradi, Elnaz; Mohammadi, Ali; Javanbakht, Mehran; Dinarvand, Rassoul; Atyabi, Fatemeh

    2016-01-01

    The aim of this work was to synthesize molecularly imprinted polymer-poly ethylene glycol-folic acid (MIP-PEG-FA) nanoparticles for use as a controlled release carrier for targeting delivery of paclitaxel (PTX) to cancer cells. MIP nanoparticles were synthesized by a mini-emulsion polymerization technique and then PEG-FA was conjugated to the surface of nanoparticles. Nanoparticles showed high drug loading and encapsulation efficiency, 15.6 ± 0.8 and 100%, respectively. The imprinting efficiency of MIPs was evaluated by binding experiments in human serum. Good selective binding and recognition were found in MIP nanoparticles. In vitro drug release studies showed that MIP-PEG-FA have a controlled release of PTX, because of the presence of imprinted sites in the polymeric structure, which makes it is suitable for sustained drug delivery. The drug release from polymeric nanoparticles was indeed higher at acidic pH. The molecular structure of MIP-PEG-FA was confirmed by Hydrogen-Nuclear Magnetic Resonance (H NMR), Fourier Transform InfraRed (FT-IR), and Attenuated Total Reflection (ATR) spectroscopy, and their thermal behaviors by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Scanning Electron Microscopy (SEM) and Photon Correlation Spectroscopy (PCS) results showed that nanoparticles have a smooth surface and spherical shape with an average size of 181 nm. MIP-PEG-FA nanoparticles showed a greater amount of intracellular uptake in folate receptor-positive cancer cells (MDA-MB-231 cells) in comparison with the non-folate nanoparticles and free PTX, with half maximal inhibitory concentrations (IC_5_0) of 4.9 ± 0.9, 7.4 ± 0.5 and 32.8 ± 3.8 nM, respectively. These results suggest that MIP-PEG-FA nanoparticles could be a potentially useful drug carrier for targeting drug delivery to cancer cells. - Highlights: • MIP-PEG-FA was synthesized as a controlled release carrier for targeting delivery to cancerous cells. • Nanoparticles

  7. Paclitaxel molecularly imprinted polymer-PEG-folate nanoparticles for targeting anticancer delivery: Characterization and cellular cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Esfandyari-Manesh, Mehdi [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Chemistry, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Darvishi, Behrad [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ishkuh, Fatemeh Azizi [Department of Chemistry, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Shahmoradi, Elnaz [Department of Chemical Engineering, Sharif University of Technology, Tehran (Iran, Islamic Republic of); Mohammadi, Ali [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Javanbakht, Mehran [Department of Chemistry, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Dinarvand, Rassoul [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Atyabi, Fatemeh, E-mail: atyabifa@tums.ac.ir [Nanotechnology Research Center,Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2016-05-01

    The aim of this work was to synthesize molecularly imprinted polymer-poly ethylene glycol-folic acid (MIP-PEG-FA) nanoparticles for use as a controlled release carrier for targeting delivery of paclitaxel (PTX) to cancer cells. MIP nanoparticles were synthesized by a mini-emulsion polymerization technique and then PEG-FA was conjugated to the surface of nanoparticles. Nanoparticles showed high drug loading and encapsulation efficiency, 15.6 ± 0.8 and 100%, respectively. The imprinting efficiency of MIPs was evaluated by binding experiments in human serum. Good selective binding and recognition were found in MIP nanoparticles. In vitro drug release studies showed that MIP-PEG-FA have a controlled release of PTX, because of the presence of imprinted sites in the polymeric structure, which makes it is suitable for sustained drug delivery. The drug release from polymeric nanoparticles was indeed higher at acidic pH. The molecular structure of MIP-PEG-FA was confirmed by Hydrogen-Nuclear Magnetic Resonance (H NMR), Fourier Transform InfraRed (FT-IR), and Attenuated Total Reflection (ATR) spectroscopy, and their thermal behaviors by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Scanning Electron Microscopy (SEM) and Photon Correlation Spectroscopy (PCS) results showed that nanoparticles have a smooth surface and spherical shape with an average size of 181 nm. MIP-PEG-FA nanoparticles showed a greater amount of intracellular uptake in folate receptor-positive cancer cells (MDA-MB-231 cells) in comparison with the non-folate nanoparticles and free PTX, with half maximal inhibitory concentrations (IC{sub 50}) of 4.9 ± 0.9, 7.4 ± 0.5 and 32.8 ± 3.8 nM, respectively. These results suggest that MIP-PEG-FA nanoparticles could be a potentially useful drug carrier for targeting drug delivery to cancer cells. - Highlights: • MIP-PEG-FA was synthesized as a controlled release carrier for targeting delivery to cancerous cells. • Nanoparticles

  8. Development of PEGylated PLGA nanoparticle for controlled and sustained drug delivery in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Mazur Steven

    2010-09-01

    Full Text Available Abstract Background The mutation in the cystic fibrosis transmembrane conductance regulator (CFTR gene results in CF. The most common mutation, ΔF508-CFTR, is a temperature-sensitive, trafficking mutant with reduced chloride transport and exaggerated immune response. The ΔF508-CFTR is misfolded, ubiquitinated, and prematurely degraded by proteasome mediated- degradation. We recently demonstrated that selective inhibition of proteasomal pathway by the FDA approved drug PS-341 (pyrazylcarbonyl-Phe-Leuboronate, a.k.a. Velcade or bortezomib ameliorates the inflammatory pathophysiology of CF cells. This proteasomal drug is an extremely potent, stable, reversible and selective inhibitor of chymotryptic threonine protease-activity. The apprehension in considering the proteasome as a therapeutic target is that proteasome inhibitors may affect proteostasis and consecutive processes. The affect on multiple processes can be mitigated by nanoparticle mediated PS-341 lung-delivery resulting in favorable outcome observed in this study. Results To overcome this challenge, we developed a nano-based approach that uses drug loaded biodegradable nanoparticle (PLGA-PEGPS-341 to provide controlled and sustained drug delivery. The in vitro release kinetics of drug from nanoparticle was quantified by proteasomal activity assay from days 1-7 that showed slow drug release from day 2-7 with maximum inhibition at day 7. For in vivo release kinetics and biodistribution, these drug-loaded nanoparticles were fluorescently labeled, and administered to C57BL6 mice by intranasal route. Whole-body optical imaging of the treated live animals demonstrates efficient delivery of particles to murine lungs, 24 hrs post treatment, followed by biodegradation and release over time, day 1-11. The efficacy of drug release in CF mice (Cftr-/- lungs was determined by quantifying the changes in proteasomal activity (~2 fold decrease and ability to rescue the Pseudomonas aeruginosa LPS (Pa

  9. A RNA-DNA Hybrid Aptamer for Nanoparticle-Based Prostate Tumor Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    John C. Leach

    2016-03-01

    Full Text Available The side effects of radio- and chemo-therapy pose long-term challenges on a cancer patient’s health. It is, therefore, highly desirable to develop more effective therapies that can specifically target carcinoma cells without damaging normal and healthy cells. Tremendous efforts have been made in the past to develop targeted drug delivery systems for solid cancer treatment. In this study, a new aptamer, A10-3-J1, which recognizes the extracellular domain of the prostate specific membrane antigen (PSMA, was designed. A super paramagnetic iron oxide nanoparticle-aptamer-doxorubicin (SPIO-Apt-Dox was fabricated and employed as a targeted drug delivery platform for cancer therapy. This DNA RNA hybridized aptamer antitumor agent was able to enhance the cytotoxicity of targeted cells while minimizing collateral damage to non-targeted cells. This SPIO-Apt-Dox nanoparticle has specificity to PSMA+ prostate cancer cells. Aptamer inhibited nonspecific uptake of membrane-permeable doxorubic to the non-target cells, leading to reduced untargeted cytotoxicity and endocytic uptake while enhancing targeted cytotoxicity and endocytic uptake. The experimental results indicate that the drug delivery platform can yield statistically significant effectiveness being more cytotoxic to the targeted cells as opposed to the non-targeted cells.

  10. Nanomedicine: Drug Delivery Systems and Nanoparticle Targeting

    International Nuclear Information System (INIS)

    Youn, Hye Won; Kang, Keon Wook; Chung, Jun Key; Lee, Dong Soo

    2008-01-01

    Applications of nanotechnology in the medical field have provided the fundamentals of tremendous improvement in precise diagnosis and customized therapy. Recent advances in nanomedicine have led to establish a new concept of theragnosis, which utilizes nanomedicines as a therapeutic and diagnostic tool at the same time. The development of high affinity nanoparticles with large surface area and functional groups multiplies diagnostic and therapeutic capacities. Considering the specific conditions related to the disease of individual patient, customized therapy requires the identification of disease target at the cellular and molecular level for reducing side effects and enhancing therapeutic efficiency. Well-designed nanoparticles can minimize unnecessary exposure of cytotoxic drugs and maximize targeted localization of administrated drugs. This review will focus on major pharmaceutical nanomaterials and nanoparticles as key components of designing and surface engineering for targeted theragnostic drug development

  11. Recovery of Drug Delivery Nanoparticles from Human Plasma Using an Electrokinetic Platform Technology.

    Science.gov (United States)

    Ibsen, Stuart; Sonnenberg, Avery; Schutt, Carolyn; Mukthavaram, Rajesh; Yeh, Yasan; Ortac, Inanc; Manouchehri, Sareh; Kesari, Santosh; Esener, Sadik; Heller, Michael J

    2015-10-01

    The effect of complex biological fluids on the surface and structure of nanoparticles is a rapidly expanding field of study. One of the challenges holding back this research is the difficulty of recovering therapeutic nanoparticles from biological samples due to their small size, low density, and stealth surface coatings. Here, the first demonstration of the recovery and analysis of drug delivery nanoparticles from undiluted human plasma samples through the use of a new electrokinetic platform technology is presented. The particles are recovered from plasma through a dielectrophoresis separation force that is created by innate differences in the dielectric properties between the unaltered nanoparticles and the surrounding plasma. It is shown that this can be applied to a wide range of drug delivery nanoparticles of different morphologies and materials, including low-density nanoliposomes. These recovered particles can then be analyzed using different methods including scanning electron microscopy to monitor surface and structural changes that result from plasma exposure. This new recovery technique can be broadly applied to the recovery of nanoparticles from high conductance fluids in a wide range of applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Biocompatible fluorescent zein nanoparticles for simultaneous bioimaging and drug delivery application

    International Nuclear Information System (INIS)

    Girija Aswathy, Ravindran; Sivakumar, Balasubramanian; Brahatheeswaran, Dhandayudhapani; Fukuda, Takahiro; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D

    2012-01-01

    We report the synthesis of 5-fluorouracil (5-FU) loaded biocompatible fluorescent zein nanoparticles. Zein is the storage protein in corn kernels that has a variety of unique characteristics and functionalities that makes zein valuable in various commercial applications. It is classified as generally recognized as safe (GRAS) by the Food and Drug Administration (FDA). We synthesized zein nanoparticles of around 800 nm in size and conjugated with quantum dot ZnS:Mn. The nanoparticle was in turn encapsulated with the drug 5-FU. The luminescent properties of these nanoparticles were studied by using fluorescence microscopy. The nanoparticles were characterized and the drug release profile was studied. The biocompatibility of zein nanoparticle and the cytotoxicity with drug-loaded nanoparticle was studied in L929 and MCF-7 cell lines. The nanoparticles were successfully employed for cellular imaging. In vitro drug release studies were also performed. The biocompatibility of the nanoparticle showed that nanoparticles at higher concentrations are compatible for cells and are expected to be promising agents for the targeted delivery of drugs in the near future

  13. Magnetic nanoparticles for targeted therapeutic gene delivery and magnetic-inducing heating on hepatoma

    International Nuclear Information System (INIS)

    Yuan, Chenyan; Zhang, Jia; Li, Hongbo; Zhang, Hao; Wang, Ling; Zhang, Dongsheng; An, Yanli

    2014-01-01

    Gene therapy holds great promise for treating cancers, but their clinical applications are being hampered due to uncontrolled gene delivery and expression. To develop a targeted, safe and efficient tumor therapy system, we constructed a tissue-specific suicide gene delivery system by using magnetic nanoparticles (MNPs) as carriers for the combination of gene therapy and hyperthermia on hepatoma. The suicide gene was hepatoma-targeted and hypoxia-enhanced, and the MNPs possessed the ability to elevate temperature to the effective range for tumor hyperthermia as imposed on an alternating magnetic field (AMF). The tumoricidal effects of targeted gene therapy associated with hyperthermia were evaluated in vitro and in vivo. The experiment demonstrated that hyperthermia combined with a targeted gene therapy system proffer an effective tool for tumor therapy with high selectivity and the synergistic effect of hepatoma suppression. (paper)

  14. Biotin-Conjugated Multilayer Poly [D,L-lactide-co-glycolide]-Lecithin-Polyethylene Glycol Nanoparticles for Targeted Delivery of Doxorubicin.

    Science.gov (United States)

    Dai, Yu; Xing, Han; Song, Fuling; Yang, Yue; Qiu, Zhixia; Lu, Xiaoyu; Liu, Qi; Ren, Shuangxia; Chen, Xijing; Li, Ning

    2016-09-01

    Multilayer nanoparticle combining the merits of liposome and polymer nanoparticle has been designed for the targeted delivery of doxorubicin (DOX) in cancer treatment. In this study, DOX-PLGA-lecithin-PEG-biotin nanoparticles (DOX-PLPB-NPs) were fabricated and functionalized with biotin for specific tumor targeting. Under the transmission electron microscopy observation, the lipid layer was found to be coated on the polymer core. The physical characteristics of PLPB-NPs were also evaluated. The confocal laser scanning microscopy confirmed the cellular uptake of nanoparticles and targeted delivery PLPB-NPs. The in vitro release experiment demonstrated a pH-depending release of DOX from drug-loaded PLPB-NPs. Cytotoxicity studies in HepG2 cells and in vivo antitumor experiment in tumor-bearing mice both proved DOX-PLPB-NPs showed the best inhibition effect of tumor proliferation. In biodistribution studies, DOX-PLPB-NPs showed a higher DOX concentration than free DOX and DOX-PLGA-lecithin-PEG nanoparticles (DOX-PLP-NPs) in tumor site, especially in 24 h, and the lowest DOX level in normal organs. The results were coincident with the strongest antitumor ability showed among in vivo antitumor experiment. Histopathology analysis demonstrated that DOX-PLPB-NPs exhibited the strongest antitumor ability and lowest cardiotoxicity. In brief, the PLPB-NPs were proved to be an efficient delivery system for tumor-targeting treatment. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  15. Delivery of human NKG2D-IL-15 fusion gene by chitosan nanoparticles to enhance antitumor immunity

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Chen; Jie, Leng; Yongqi, Wang [Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009 (China); Weiming, Xiao [Department of Gastroenterology, The Second Clinical Medical College, Yangzhou University, Yangzhou, 225009 (China); Juqun, Xi [Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, 225009 (China); Yanbing, Ding [Department of Gastroenterology, The Second Clinical Medical College, Yangzhou University, Yangzhou, 225009 (China); Li, Qian [Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009 (China); Xingyuan, Pan [Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, 225009 (China); Mingchun, Ji [Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009 (China); Weijuan, Gong, E-mail: wjgong@yzu.edu.cn [Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009 (China); Department of Gastroenterology, The Second Clinical Medical College, Yangzhou University, Yangzhou, 225009 (China); Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, 225009 (China); Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, 225009 (China); Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009 (China)

    2015-07-31

    Nanoparticles are becoming promising carriers for gene delivery because of their high capacity in gene loading and low cell cytotoxicity. In this study, a chitosan-based nanoparticle encapsulated within a recombinant pcDNA3.1-dsNKG2D-IL-15 plasmid was generated. The fused dsNKG2D-IL-15 gene fragment consisted of double extracellular domains of NKG2D with IL-15 gene at downstream. The average diameter of the gene nanoparticles ranged from 200 nm to 400 nm, with mean zeta potential value of 53.8 ± 6.56 mV. The nanoparticles which were loaded with the dsNKG2D-IL-15 gene were uptaken by tumor cells with low cytotoxicity. Tumor cells pre-transfected by gene nanopartilces stimulated NK and T cells in vitro. Intramuscular injection of gene nanoparticles suppressed tumor growth and prolonged survival of tumor-bearing mice through activation of NK and CD8{sup +} T cells. Thus, chitosan-based nanoparticle delivery of dsNKG2D-IL-15 gene vaccine can be potentially used for tumor therapy. - Highlights: • Generation of a nanoparticle for delivery of dsNKG2D-IL-15 gene. • Characterization of the gene nanoparticle. • Antitumor activity mediated by the gene nanoparticle.

  16. Delivery of human NKG2D-IL-15 fusion gene by chitosan nanoparticles to enhance antitumor immunity

    International Nuclear Information System (INIS)

    Yan, Chen; Jie, Leng; Yongqi, Wang; Weiming, Xiao; Juqun, Xi; Yanbing, Ding; Li, Qian; Xingyuan, Pan; Mingchun, Ji; Weijuan, Gong

    2015-01-01

    Nanoparticles are becoming promising carriers for gene delivery because of their high capacity in gene loading and low cell cytotoxicity. In this study, a chitosan-based nanoparticle encapsulated within a recombinant pcDNA3.1-dsNKG2D-IL-15 plasmid was generated. The fused dsNKG2D-IL-15 gene fragment consisted of double extracellular domains of NKG2D with IL-15 gene at downstream. The average diameter of the gene nanoparticles ranged from 200 nm to 400 nm, with mean zeta potential value of 53.8 ± 6.56 mV. The nanoparticles which were loaded with the dsNKG2D-IL-15 gene were uptaken by tumor cells with low cytotoxicity. Tumor cells pre-transfected by gene nanopartilces stimulated NK and T cells in vitro. Intramuscular injection of gene nanoparticles suppressed tumor growth and prolonged survival of tumor-bearing mice through activation of NK and CD8 + T cells. Thus, chitosan-based nanoparticle delivery of dsNKG2D-IL-15 gene vaccine can be potentially used for tumor therapy. - Highlights: • Generation of a nanoparticle for delivery of dsNKG2D-IL-15 gene. • Characterization of the gene nanoparticle. • Antitumor activity mediated by the gene nanoparticle

  17. Enhanced rifampicin delivery to alveolar macrophages by solid lipid nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Chuan Junlan [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China); Li Yanzhen [Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery Technology and Pharmacokinetics (China); Yang Likai; Sun Xun [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China); Zhang Qiang [Peking University, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences (China); Gong Tao, E-mail: gongtaoy@126.com; Zhang Zhirong, E-mail: zrzzl@vip.sina.com [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China)

    2013-05-15

    The present study aimed at developing a drug delivery system targeting the densest site of tuberculosis infection, the alveolar macrophages (AMs). Rifampicin (RFP)-loaded solid lipid nanoparticles (RFP-SLNs) with an average size of 829.6 {+-} 16.1 nm were prepared by a modified lipid film hydration method. The cytotoxicity of RFP-SLNs to AMs and alveolar epithelial type II cells (AECs) was examined using MTT assays. The viability of AMs and AECs was above 80 % after treatment with RFP-SLNs, which showed low toxicity to both AMs and AECs. Confocal Laser Scanning Microscopy was employed to observe the interaction between RFP-SLNs and both AMs and AECs. After incubating the cells with RFP-SLNs for 2 h, the fluorescent intensity in AMs was more and remained longer (from 0.5 to 12 h) when compared with that in AECs (from 0.5 to 8 h). In vitro uptake characteristics of RFP-SLNs in AMs and AECs were also investigated by detection of intracellular RFP by High performance liquid chromatography. Results showed that RFP-SLNs delivered markedly higher RFP into AMs (691.7 ng/mg in cultured AMs, 662.6 ng/mg in primary AMs) than that into AECs (319.2 ng/mg in cultured AECs, 287.2 ng/mg in primary AECs). Subsequently, in vivo delivery efficiency and the selectivity of RFP-SLNs were further verified in Sprague-Dawley rats. Under pulmonary administration of RFP-SLNs, the amount of RFP in AMs was significantly higher than that in AECs at each time point. Our results demonstrated that solid lipid nanoparticles are a promising strategy for the delivery of rifampicin to alveolar macrophages selectively.

  18. Fabrication and characterization of sol-gel based nanoparticles for drug delivery

    Science.gov (United States)

    Yadav, Reeta

    Nanogels are cross linked polymeric sol-gel based nanoparticles that offer an interior network for incorporation and protection of biomolecules, exhibiting unique advantages for polymer based delivery systems. We have successfully synthesized stable sol-gel nanoparticles by means of [a] silicification reactions using cationic peptides like polylysine as gelating agents, and [b] lyophilization of sol-gels. Macromolecules such as Hemoglobin and Glucose Oxidase and small molecules such as Sodium Nitroprusside (SNP) and antibiotics were encapsulated within the nanogels. We have used transmission electron microscopy, dynamic light scattering, zeta potential analysis, and spectroscopy to perform a physicochemical characterization of the nanogels resulting from the two approaches. Our studies have indicated that the nanogel encapsulated proteins and small molecules remain intact, stable and functional. A Hydrogen Peroxide (H2O2) and Nitric Oxide (NO) generating drug carrier was synthesized using these nanogels and the effect of generation of H2O2 from Glucose Oxidase encapsulated nanogels and NO from SNP encapsulated nanogels was tested on E.coli. The results show that the nanoparticles exert antimicrobial activity against E.Coli, in addition NO generating nanogels potentiated H2O2 generating nanogels induced killing. These data suggest that these NO and H2O2 releasing nanogels have the potential to serve as a novel class of antimicrobials for the treatment of multidrug resistant bacteria. The unique properties of these protein/drug incorporated nanogels raise the prospect of fine tailoring to specific applications such as drug delivery and bio imaging.

  19. Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations

    Science.gov (United States)

    Özcan, İpek; Azizoğlu, Erkan; Şenyiğit, Taner; Özyazıcı, Mine; Özer, Özgen

    2013-01-01

    The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders. PMID:23390364

  20. Cationic albumin-conjugated pegylated nanoparticles as novel drug carrier for brain delivery.

    Science.gov (United States)

    Lu, Wei; Zhang, Yan; Tan, Yu-Zhen; Hu, Kai-Li; Jiang, Xin-Guo; Fu, Shou-Kuan

    2005-10-20

    In this paper, a novel drug carrier for brain delivery, cationic bovine serum albumin (CBSA) conjugated with poly(ethyleneglycol)-poly(lactide) (PEG-PLA) nanoparticle (CBSA-NP), was developed and its effects were evaluated. The copolymers of methoxy-PEG-PLA and maleimide-PEG-PLA were synthesized by ring opening polymerization of D,L-lactide initiated by methoxy-PEG and maleimide-PEG, respectively, which were applied to prepare pegylated nanoparticles by means of double emulsion and solvent evaporation procedure. Native bovine serum albumin (BSA) was cationized and thiolated, followed by conjugation through the maleimide function located at the distal end of PEG surrounding the nanoparticle's surface. Transmission electron micrograph (TEM) and dynamic light scattering results showed that CBSA-NP had a round and regular shape with a mean diameter around 100 nm. Surface nitrogen was detected by X-ray photoelectron spectroscopy (XPS), and colloidal gold stained around the nanoparticle's surface was visualized in TEM, which proved that CBSA was covalently conjugated onto its surface. To evaluate the effects of brain delivery, BSA conjugated with pegylated nanoparticles (BSA-NP) was used as the control group and 6-coumarin was incorporated into the nanoparticles as the fluorescent probe. The qualitative and quantitative results of CBSA-NP uptake experiment compared with those of BSA-NP showed that rat brain capillary endothelial cells (BCECs) took in much more CBSA-NP than BSA-NP at 37 degrees C, at different concentrations and time incubations. After a dose of 60 mg/kg CBSA-NP or BSA-NP injection in mice caudal vein, fluorescent microscopy of brain coronal sections showed a higher accumulation of CBSA-NP in the lateral ventricle, third ventricle and periventricular region than that of BSA-NP. There was no difference on BCECs' viability between CBSA-conjugated and -unconjugated pegylated nanoparticles. The significant results in vitro and in vivo showed that CBSA-NP was

  1. Contrast ultrasound targeted treatment of gliomas in mice via drug-bearing nanoparticle delivery and microvascular ablation.

    Science.gov (United States)

    Burke, Caitlin W; Price, Richard J

    2010-12-15

    We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas.

  2. Construction of hydroxypropyl-{beta}-cyclodextrin copolymer nanoparticles and targeting delivery of paclitaxel

    Energy Technology Data Exchange (ETDEWEB)

    Miao Qinghua; Li Suping; Han Siyuan [National Center for Nanoscience and Technology of China, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety (China); Wang Zhi, E-mail: wangzhi@jlu.edu.cn [Jilin University, Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education (China); Wu Yan, E-mail: wuy@nanoctr.cn; Nie Guangjun, E-mail: niegj@nanoctr.cn [National Center for Nanoscience and Technology of China, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety (China)

    2012-08-15

    A novel amphiphilic copolymer with p-maleimidophenyl isocyanate-hydroxypropyl-{beta}-cyclodextrin-polylactide-1, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine to generate copolymer nanoparticles (NPs) has been designed. In order to develop an active targeting system, integrin {alpha}{sub v}{beta}{sub 3}-specific targeting peptide cyclo(Arg-Gly-Asp-D-Phe-Cys), cRGD, was conjugated to the surface of NPs (NPs-RGD). These NPs were used to encapsulate anti-tumor drug, paclitaxel. The resulting NPs exhibited high drug-loading capacity and controlled drug release in vitro at acidic pH. In vitro cytotoxicity assay demonstrates that paclitaxel-loaded NPs-RGD significantly inhibited B16 tumor cell (high {alpha}{sub v}{beta}{sub 3}) proliferation relative to free paclitaxel and paclitaxel-loaded NPs at high concentrations. Paclitaxel-loaded NPs-RGD localized mainly in lysosomes in B16 cells as revealed by confocal microscopy. These results suggest a novel strategy for fabrication-functionalizing hydroxypropyl-{beta}-cyclodextrin copolymer nanoparticles for targeting delivery of paclitaxel to integrin {alpha}{sub v}{beta}{sub 3}-rich tumor cells. These nanocarriers can be readily extended to couple other bioactive molecules for active targeting and delivery of various chemotherapeutic drugs.

  3. Charge-reversal nanoparticles: novel targeted drug delivery carriers.

    Science.gov (United States)

    Chen, Xinli; Liu, Lisha; Jiang, Chen

    2016-07-01

    Spurred by significant progress in materials chemistry and drug delivery, charge-reversal nanocarriers are being developed to deliver anticancer formulations in spatial-, temporal- and dosage-controlled approaches. Charge-reversal nanoparticles can release their drug payload in response to specific stimuli that alter the charge on their surface. They can elude clearance from the circulation and be activated by protonation, enzymatic cleavage, or a molecular conformational change. In this review, we discuss the physiological basis for, and recent advances in the design of charge-reversal nanoparticles that are able to control drug biodistribution in response to specific stimuli, endogenous factors (changes in pH, redox gradients, or enzyme concentration) or exogenous factors (light or thermos-stimulation).

  4. Preventative vaccine-loaded mannosylated chitosan nanoparticles intended for nasal mucosal delivery enhance immune responses and potent tumor immunity.

    Science.gov (United States)

    Yao, Wenjun; Peng, Yixing; Du, Mingzhu; Luo, Juan; Zong, Li

    2013-08-05

    Chitosan (CS) has been extensively used as a protein drug and gene delivery carrier, but its delivery efficiency is unsatisfactory. In this study, a mannose ligand was used to modify CS, which could enhance the delivery efficiency of CS via mannose receptor-mediated endocytosis. A preventative anti-GRP DNA vaccine (pCR3.1-VS-HSP65-TP-GRP6-M2, pGRP) was condensed with mannosylated chitosan (MCS) to form MCS/pGRP nanoparticles. Nanoparticles were intranasally administered in a subcutaneous mice prostate carcinoma model to evaluate the efficacy on inhibition of the growth of tumor cells. The titers of anti-GRP IgG that lasted for 11 weeks were significantly higher than that for administration of CS/pGRP nanoparticles (p intramuscular administration of a pGRP solution (p nanoparticles could suppress the growth of tumor cells. The average tumor weight (0.79 ± 0.30 g) was significantly lower than that in the CS/pGRP nanoparticle group (1.69 ± 0.15 g) (p nanoparticles bound with C-type lectin receptors on macrophages. MCS was an efficient targeting gene delivery carrier and could be used in antitumor immunotherapy.

  5. An Overview of Chitosan Nanoparticles and Its Application in Non-Parenteral Drug Delivery

    Directory of Open Access Journals (Sweden)

    Munawar A. Mohammed

    2017-11-01

    Full Text Available The focus of this review is to provide an overview of the chitosan based nanoparticles for various non-parenteral applications and also to put a spotlight on current research including sustained release and mucoadhesive chitosan dosage forms. Chitosan is a biodegradable, biocompatible polymer regarded as safe for human dietary use and approved for wound dressing applications. Chitosan has been used as a carrier in polymeric nanoparticles for drug delivery through various routes of administration. Chitosan has chemical functional groups that can be modified to achieve specific goals, making it a polymer with a tremendous range of potential applications. Nanoparticles (NP prepared with chitosan and chitosan derivatives typically possess a positive surface charge and mucoadhesive properties such that can adhere to mucus membranes and release the drug payload in a sustained release manner. Chitosan-based NP have various applications in non-parenteral drug delivery for the treatment of cancer, gastrointestinal diseases, pulmonary diseases, drug delivery to the brain and ocular infections which will be exemplified in this review. Chitosan shows low toxicity both in vitro and some in vivo models. This review explores recent research on chitosan based NP for non-parenteral drug delivery, chitosan properties, modification, toxicity, pharmacokinetics and preclinical studies.

  6. Mannan-Modified PLGA Nanoparticles for Targeted Gene Delivery

    Directory of Open Access Journals (Sweden)

    Fansheng Kong

    2012-01-01

    Full Text Available The studies of targeted gene delivery nanocarriers have gained increasing attention during the past decades. In this study, mannan modified DNA loaded bioadhesive PLGA nanoparticles (MAN-DNA-NPs were investigated for targeted gene delivery to the Kupffer cells (KCs. Bioadhesive PLGA nanoparticles were prepared and subsequently bound with pEGFP. Following the coupling of the mannan-based PE-grafted ligands (MAN-PE with the DNA-NPs, the MAN-DNA-NPs were delivered intravenously to rats. The transfection efficiency was determined from the isolated KCs and flow cytometry was applied for the quantitation of gene expression after 48 h post transfection. The size of the MAN-DNA-NPs was found to be around 190 nm and the Zeta potential was determined to be −15.46mV. The pEGFP binding capacity of MAN-DNA-NPs was (88.9±5.8% and the in vitro release profiles of the MAN-DNA-NPs follow the Higuchi model. When compared with non-modified DNA-NPs and Lipofectamine 2000-DNA, MAN-DNA-NPs produced the highest gene expressions, especially in vivo. The in vivo data from flow cytometry analysis showed that MAN-DNA-NPs displayed a remarkably higher transfection efficiency (39% than non-modified DNA-NPs (25% and Lipofectamine 2000-DNA (23% in KCs. The results illustrate that MAN-DNA-NPs have the ability to target liver KCs and could function as promising active targeting drug delivery vectors.

  7. Magnetic nanoparticles for local drug delivery using magnetic implants

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Pacheco, Rodrigo [Instituto Universitario de Investigacion en Nanociencia de Aragon (INA), Universidad de Zaragoza, Edif. Inter. II, 50009 Zaragoza (Spain); Marquina, Clara [Instituto de Ciencia de Materiales de Aragon (ICMA), CSIC-Universidad de Zaragoza, Facultad de Ciencias, 50009 Zaragoza (Spain); Gabriel Valdivia, J. [Instituto Universitario de Investigacion en Nanociencia de Aragon (INA), Universidad de Zaragoza, Edif. Inter. II, 50009 Zaragoza (Spain); Hospital Clinico Universitario ' Lozano Blesa' , Avda Gomez Laguna, 50009 Zaragoza (Spain)] (and others)

    2007-04-15

    Magnetic nanoparticles are good candidates used for the targeted delivery of anti-tumor agents. They can be concentrated on a desired region, reducing collateral effects and improving the efficiency of the chemotherapy. We propose a method in which permanent magnets are implanted by laparoscopic technique directly in the affected organ. This method proposes the use of FeC nanoparticles, which are loaded with doxorubicin and injected intravenously. The particles, once attracted to the magnet, release the drug at the tumor region. This method seems to be more promising and effective than that based on the application of external magnetic fields.

  8. Magnetic nanoparticles for local drug delivery using magnetic implants

    International Nuclear Information System (INIS)

    Fernandez-Pacheco, Rodrigo; Marquina, Clara; Gabriel Valdivia, J.

    2007-01-01

    Magnetic nanoparticles are good candidates used for the targeted delivery of anti-tumor agents. They can be concentrated on a desired region, reducing collateral effects and improving the efficiency of the chemotherapy. We propose a method in which permanent magnets are implanted by laparoscopic technique directly in the affected organ. This method proposes the use of FeC nanoparticles, which are loaded with doxorubicin and injected intravenously. The particles, once attracted to the magnet, release the drug at the tumor region. This method seems to be more promising and effective than that based on the application of external magnetic fields

  9. Red Blood Cell Membrane-Cloaked Nanoparticles For Drug Delivery

    Science.gov (United States)

    Carpenter, Cody Westcott

    Herein we describe the development of the Red Blood Cell coated nanoparticle, RBC-NP. Purified natural erythrocyte membrane is used to coat drug-loaded poly(lacticco-glycolic acid) (PLGA). Synthetic PLGA co-polymer is biocompatible and biodegradable and has already received US FDA approval for drug-delivery and diagnostics. This work looks specifically at the retention of immunosuppressive proteins on RBC-NPs, right-sidedness of natural RBC membranes interfacing with synthetic polymer nanoparticles, sustained and retarded drug release of RBC-NPs as well as further surface modification of RBC-NPs for increased targeting of model cancer cell lines.

  10. Differences in physicochemical properties to consider in the design, evaluation and choice between microparticles and nanoparticles for drug delivery.

    Science.gov (United States)

    Otto, Daniel P; Otto, Anja; de Villiers, Melgardt M

    2015-05-01

    The increase in the development of novel nanoparticle drug delivery systems makes the choice between micro- and nanoscale drug delivery systems ubiquitous. Changes in physical and chemical properties between micro- to nanosized particles give them different properties that influence their physiological, anatomical and clinical behavior and therefore potential application. This review focuses on the effect changes in the surface-to-volume ratio have on the thermal properties, solubility, dissolution and crystallization of micro- versus nanosized drug delivery systems. With these changes in the physicochemical properties in mind, the review covers computational and biophysical approaches to the design and evaluation of micro- and nanodelivery systems. The emphasis of the review is on the effect these properties have on clinical performance in terms of drug release, tissue retention, biodistribution, efficacy, toxicity and therefore choice of delivery system. Ultimately, the choice between micro- and nanometer-sized delivery systems is not straightforward. However, if the fundamental differences in physical and chemical properties are considered, it can be much easier to make a rational choice of the appropriate drug delivery system size.

  11. Preparation and characterization of vinculin-targeted polymer-lipid nanoparticle as intracellular delivery vehicle.

    Science.gov (United States)

    Wang, Junping; Ornek-Ballanco, Ceren; Xu, Jiahua; Yang, Weiguo; Yu, Xiaojun

    2013-01-01

    Intracellular delivery vehicles have been extensively investigated as these can serve as an effective tool in studying the cellular mechanism, by delivering functional protein to specific locations of the cells. In the current study, a polymer-lipid nanoparticle (PLN) system was developed as an intracellular delivery vehicle specifically targeting vinculin, a focal adhesion protein associated with cellular adhesive structures, such as focal adhesions and adherens junctions. The PLNs possessed an average size of 106 nm and had a positively charged surface. With a lower encapsulation efficiency 32% compared with poly(lactic-co-glycolic) acid (PLGA) nanoparticles (46%), the PLNs showed the sustained release profile of model drug BSA, while PLGA nanoparticles demonstrated an initial burst-release property. Cell-uptake experiments using mouse embryonic fibroblasts cultured in fibrin-fibronectin gels observed, under confocal microscope, that the anti-vinculin conjugated PLNs could successfully ship the cargo to the cytoplasm of fibroblasts, adhered to fibronectin-fibrin. With the use of cationic lipid, the unconjugated PLNs were shown to have high gene transfection efficiency. Furthermore, the unconjugated PLNs had nuclear-targeting capability in the absence of nuclear-localization signals. Therefore, the PLNs could be manipulated easily via different type of targeting ligands and could potentially be used as a powerful tool for cellular mechanism study, by delivering drugs to specific cellular organelles.

  12. Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

    Science.gov (United States)

    Etame, Arnold B.

    The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non

  13. Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles

    Science.gov (United States)

    A central challenge to the development of protein-based therapeutics is the inefficiency of delivery of protein cargo across the mammalian cell membrane, including escape from endosomes. Here we report that combining bioreducible lipid nanoparticles with negatively supercharged Cre recombinase or an...

  14. PEG-detachable lipid-polymer hybrid nanoparticle for delivery of chemotherapy drugs to cancer cells.

    Science.gov (United States)

    Du, Jiang-bo; Song, Yan-feng; Ye, Wei-liang; Cheng, Ying; Cui, Han; Liu, Dao-zhou; Liu, Miao; Zhang, Bang-le; Zhou, Si-yuan

    2014-08-01

    The experiment aimed to increase the drug-delivery efficiency of poly-lactic-co-glycolic acid (PLGA) nanoparticles. Lipid-polymer hybrid nanoparticles (LPNs-1) were prepared using PLGA as a hydrophobic core and FA-PEG-hyd-DSPE as an amphiphilic shell. Uniform and spherical nanoparticles with an average size of 185 nm were obtained using the emulsification solvent evaporation method. The results indicated that LPNs-1 showed higher drug loading compared with naked PLGA nanoparticles (NNPs). Drug release from LPNs-1 was faster in an acidic environment than in a neutral environment. LPNs-1 showed higher cytotoxicity on KB cells, A549 cells, MDA-MB-231 cells, and MDA-MB-231/ADR cells compared with free doxorubicin (DOX) and NNPs. The results also showed that, compared with free DOX and NNPs, LPNs-1 delivered more DOX to the nuclear of KB cells and MDA-MB-231/ADR cells. LPNs-1 induced apoptosis in KB cells and MDA-MB-231/ADR cells in a dose-dependent manner. The above data indicated that DOX-loaded LPNs-1 could kill not only normal tumor cells but also drug-resistant tumor cells. These results indicated that modification of PLGA nanoparticles with FA-PEG-hyd-DSPE could considerably increase the drug-delivery efficiency and LPNs-1 had potential in the delivery of chemotherapeutic agents in the treatment of cancer.

  15. Elastin-Like Recombinamers As Smart Drug Delivery Systems.

    Science.gov (United States)

    Arias, F Javier; Santos, Mercedes; Ibanez-Fonseca, Arturo; Pina, Maria Jesus; Serrano, Sofía

    2018-02-19

    Drug delivery systems that are able to control the release of bioactive molecules and designed to carry drugs to target sites are of particular interest for tissue therapy. Moreover, systems comprising materials that can respond to environmental stimuli and promote self-assembly and higher order supramolecular organization are especially useful in the biomedical field. Objetive: This review focuses on biomaterials suitable for this purpose and that include elastin-like recombinamers (ELRs), a class of proteinaceous polymers bioinspired by natural elastin, designed using recombinant technologies. The self-assembly and thermoresponsive behaviour of these systems, along with their biodegradability, biocompatibility and well-defined composition as a result of their tailormade design, make them particularly attractive for controlled drug delivery. ELR-based delivery systems that allow targeted delivery are reviewed, especially ELR-drug recombinant fusion constructs, ELR-drug systems chemically bioconjugated in their monomeric and soluble forms, and drug encapsulation by nanoparticle-forming ELRs. Subsequently, the review focuses on those drug carriers in which smart release is triggered by pH or temperature with a particular focus on cancer treatments. Systems for controlled drug release based on depots and hydrogels that act as both a support and reservoir in which drugs can be stored will be described, and their applications in drug delivery discussed. Finally, smart drug-delivery systems not based on ELRs, including those comprising proteins, synthetic polymers and non-polymeric systems, will also be briefly discussed. Several different constructions based on ELRs are potential candidates for controlled drug delivery to be applied in advanced biomedical treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Nanoparticles functionalized with supramolecular host-guest systems for nanomedicine and healthcare.

    Science.gov (United States)

    Wu, Zilong; Song, Nan; Menz, Ryan; Pingali, Bharadwaj; Yang, Ying-Wei; Zheng, Yuebing

    2015-05-01

    Synthetic macrocyclic host compounds can interact with suitable guest molecules via noncovalent interactions to form functional supramolecular systems. With the synergistic integration of the response of molecules and the unique properties at the nanoscale, nanoparticles functionalized with the host-guest supramolecular systems have shown great potentials for a broad range of applications in the fields of nanoscience and nanotechnology. In this review article, we focus on the applications of the nanoparticles functionalized with supramolecular host-guest systems in nanomedicine and healthcare, including therapeutic delivery, imaging, sensing and removal of harmful substances. A large number of examples are included to elucidate the working mechanisms, advantages, limitations and future developments of the nanoparticle-supramolecule systems in these applications.

  17. Membrane-Mimic Nanoparticles for Drug and Gene Delivery

    KAUST Repository

    Alamoudi, Kholod

    2017-12-01

    Nanoscale organic particles have gained a prominent role in drug and gene delivery field. As the nature of the nanoparticle’s (NPs) surface plays a major role in their targeting efficiency, bioavailability, and cytotoxicity, membrane-mimic nanoparticles are considered highly attractive materials for in vivo and in vitro applications. Synthetic membrane vesicles (liposomes) and nanoconstructs built with native cancer cellular membrane are excellent scaffolds to improve cellular delivery. Liposomes have been extensively used due to their high loading capacity, biocompatibility and biodegradability. However, modifications with stimuli responsive materials are highly needed to improve their stability and turn them active participants in controlled delivery. Towards a nature inspired approach, reconstructed bilayers from cell membrane are a good candidate to enhance NP’s targeting ability and biocompatibility. The primary focus of this research is to develop smart responsive (lipid) membrane coated NPs with surface modifications for controlled and targeted drug and/or gene delivery for application in cancer therapy. Three approaches have been developed, namely i) liposomes as thermoresponsive nanocarriers for the delivery of genetic material; ii) magnetically photosensitive liposome hybrids and iii) biomimetic periodic mesoporous organo silica engineered for better a biocompatibility and targeting capabilities. In the first project synthetic liposomes were loaded with ammonium bicarbonate salt (ABC) and siRNA. The combination of lipids chosen and the relative ratios allowed the rapid release of the genetic material to the multi drug resistant cancer cells studied, upon external heat trigger. This design has improved the gene silencing efficiency via successful endosomal escape. In the second project, SPIO@Au nanoparticles were imbedded in the lipid bilayer to produce a photo/thermal responsive carrier that could be also used in cell imaging besides gene transfection

  18. Multifunctional DNA-gold nanoparticles for targeted doxorubicin delivery.

    Science.gov (United States)

    Alexander, Colleen M; Hamner, Kristen L; Maye, Mathew M; Dabrowiak, James C

    2014-07-16

    In this report we describe the synthesis, characterization, and cytotoxic properties of DNA-capped gold nanoparticles having attached folic acid (FA), a thermoresponsive polymer (p), and/or poly(ethylene glycol) (PEG) oligomers that could be used to deliver the anticancer drug doxorubicin (DOX) in chemotherapy. The FA-DNA oligomer used in the construction of the delivery vehicle was synthesized through the reaction of the isolated folic acid N-hydroxysuccinimide ester with the amino-DNA and the conjugated DNA product was purified using high performance liquid chromatography (HPLC). This approach ultimately allowed control of the amount of FA attached to the surface of the delivery vehicle. Cytotoxicity studies using SK-N-SH neuroblastoma cells with drug loaded delivery vehicles were carried out using a variety of exposure times (1-48 h) and recovery times (1-72 h), and in order to access the effects of varying amounts of attached FA, in culture media deficient in FA. DOX loaded delivery vehicles having 50% of the DNA strands with attached FA were more cytotoxic than when all of the strands contained FA. Since FA stimulates cell growth, the reduced cytotoxicity of vehicles fully covered with FA suggests that the stimulatory effects of FA can more than compensate for the cytotoxic effects of the drug on the cell population. While attachment of hexa-ethylene glycol PEG(18) to the surface of the delivery vehicle had no effect on cytotoxicity, 100% FA plus the thermoresponsive polymer resulted in IC50 = 0.48 ± 0.01 for an exposure time of 24 h and a recovery time of 1 h, which is an order of magnitude more cytotoxic than free DOX. Confocal microscopic studies using fluorescence detection showed that SK-N-SH neuroblastoma cells exposed to DOX-loaded vehicles have drug accumulation inside the cell and, in the case of vehicles with attached FA and thermoresponsive polymer, the drug appears more concentrated. Since the biological target of DOX is DNA, the latter

  19. Bioactivity of Hybrid Polymeric Magnetic Nanoparticles and Their Applications in Drug Delivery.

    Science.gov (United States)

    Mohammed, Leena; Ragab, Doaa; Gomaa, Hassan

    2016-01-01

    Engineered magnetic nanoparticles (MNPs) possess unique properties and hold great potential in biomedicine and clinical applications. With their magnetic properties and their ability to work at cellular and molecular level, MNP have been applied both in-vitro and in-vivo in targeted drug delivery and imaging. Focusing on Iron Oxide Superparamagnetic nanoparticles (SPIONs), this paper elaborates on the recent advances in development of hybrid polymeric-magnetic nanoparticles. Their main applications in drug delivery include Chemotherapeutics, Hyperthermia treatment, Radio-therapeutics, Gene delivary, and Biotheraputics. Physiochemical properties such as size, shape, surface and magnetic properties are key factors in determining their behavior. Additionally tailoring SPIONs surface is often vital for desired cell targetting and improved efficiency. Polymer coating is specifically reviewed with brief discussion of SPIONs administration routes. Commonly used drug release models for describing release mechanisms and the nanotoxicity aspects are also discussed. This review focus on superparamagnetic nanoparticles coated with different types of polymers starting with the key physiochemical features that dominate their behavior. The importance of surface modification is addressed. Subsequently, the major classes of polymer modified iron oxide nanoparticles is demonstrated according to their clinical use and application. Clinically approved nanoparticles are then addressed and the different routes of administration are mentioned. Lastly, mathematical models of drug release profile of the common used nanoparticles are addressed. MNPs emerging in recent medicine are remarkable for both imaging and therapeutics, particularly, as drug carriers for their great potential in targeted delivery and cancer treatment. Targeting ability and biocompatibility can be improved though surface coating which provides a mean to alter the surface features including physical characteristics and

  20. A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system.

    Science.gov (United States)

    Wang, Shaowei; Wei, Xiaochun; Sun, Xiaojuan; Chen, Chongwei; Zhou, Jingming; Zhang, Ge; Wu, Heng; Guo, Baosheng; Wei, Lei

    2018-01-01

    Cartilage degeneration affects millions of people but preventing its degeneration is a big challenge. Although RNA interference (RNAi) has been used in human trials via silencing specific genes, the cartilage RNAi has not been possible to date because the cartilage is an avascular and very dense tissue with very low permeability. The objective of this study was to develop and validate a novel lipid nanoparticle (LNP)-siRNA delivery system that can prevent cartilage degeneration by knocking down specific genes. LNP transfection efficiency was evaluated in vitro and ex vivo. Indian Hedgehog ( Ihh ) has been correlated with cartilage degeneration. The in vivo effects of LNP-Ihh siRNA complexes on cartilage degeneration were evaluated in a rat model of surgery-induced osteoarthritis (OA). In vitro, 100% of chondrocytes were transfected with siRNA in the LNP-siRNA group. In accordance with the cell culture results, red positive signals could be detected even in the deep layer of cartilage tissue cultures treated by LNP-beacon. In vivo data showed that LNP is specific for cartilage, since positive signals were detected by fluorescence molecular tomography and confocal microscopy in joint cartilage injected with LNP-beacon, but not on the surface of the synovium. In the rat model of OA, intraarticular injection of LNP-Ihh siRNA attenuated OA progression, and PCR results showed LNP-Ihh siRNA exerted a positive impact on anabolic metabolism and negative impact on catabolic metabolism. This study demonstrates that our LNP-RNAi delivery system has a significantly chondroprotective effect that attenuates cartilage degeneration and holds great promise as a powerful tool for treatment of cartilage diseases by knocking down specific genes.

  1. Design, development and characterization of multi-functionalized gold nanoparticles for biodetection and targeted boron delivery in BNCT applications

    Energy Technology Data Exchange (ETDEWEB)

    Mandal, Subhra [Department of Tumor Immunology, Radboud University Nijmegen Medical Centre (Netherlands); Bakeine, Gerald J., E-mail: Jamesbakeine1@yahoo.com [Department of Internal Medicine and Therapeutics-Section of Clinical Toxicology, University of Pavia, Piazza Botta 10, 27100 Pavia (Italy); Krol, Silke [Institute of Neurology, Fondazione IRCCS Carlo Besta, Milan (Italy); Ferrari, Cinzia; Clerici, Anna M.; Zonta, Cecilia; Cansolino, Laura [Department of Surgery, Laboratory of Experimental Surgery, University of Pavia (Italy); Ballarini, Francesca [Department of Nuclear and Theoretical Physics, University of Pavia (Italy); Bortolussi, Silva [Department of Nuclear and Theoretical Physics, University of Pavia (Italy)] [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy); Stella, Subrina; Protti, Nicoletta [Department of Nuclear and Theoretical Physics, University of Pavia (Italy); Bruschi, Piero [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy); Altieri, Saverio [Department of Nuclear and Theoretical Physics, University of Pavia (Italy)] [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy)

    2011-12-15

    The aim of this study is to optimize targeted boron delivery to cancer cells and its tracking down to the cellular level. To this end, we describe the design and synthesis of novel nanovectors that double as targeted boron delivery agents and fluorescent imaging probes. Gold nanoparticles were coated with multilayers of polyelectrolytes functionalized with the fluorescent dye (FITC), boronophenylalanine and folic acid. In vitro confocal fluorescence microscopy demonstrated significant uptake of the nanoparticles in cancer cells that are known to overexpress folate receptors. - Highlights: Black-Right-Pointing-Pointer Synthesis of multi-labeled gold nanoparticles for selective boron delivery to tumor cells. Black-Right-Pointing-Pointer Tumor selectivity is achieved through folic acid receptor targeting. Black-Right-Pointing-Pointer Optical fluorescent microscopy allows tracking of cellular uptake of the gold nanoparticle. Black-Right-Pointing-Pointer In vitro tests demonstrate selective nanoparticle up in folate receptor positive tumor cells.

  2. Development and evaluation of Desvenlafaxine loaded PLGA-chitosan nanoparticles for brain delivery

    Directory of Open Access Journals (Sweden)

    Gui-Feng Tong

    2017-09-01

    Full Text Available Depression is a debilitating psychiatric condition that remains the second most common cause of disability worldwide. Currently, depression affects more than 4 per cent of the world’s population. Most of the drugs intended for clinical management of depression augment the availability of neurotransmitters at the synapse by inhibiting their neuronal reuptake. However, the therapeutic efficacy of antidepressants is often compromised as they are unable to reach brain by the conventional routes of administration. The purpose of the present study was to reconnoiter the potential of mucoadhesive PLGA-chitosan nanoparticles for the delivery of encapsulated Desvenlafaxine to the brain by nose to brain delivery route for superior pharmacokinetic and pharmacodynamic profile of Desvenlafaxine. Desvenlafaxine loaded PLGA-chitosan nanoparticles were prepared by solvent emulsion evaporation technique and optimized for various physiochemical characteristics. The antidepressant efficacy of optimized Desvenlafaxine was evaluated in various rodent depression models together with the biochemical estimation of monoamines in their brain. Further, the levels of Desvenlafaxine in brain and blood plasma were determined at various time intervals for calculation of different pharmacokinetic parameters. The optimized Desvenlafaxine loaded PLGA-chitosan nanoparticles (∼172 nm/+35 mV on intranasal administration significantly reduced the symptoms of depression and enhanced the level of monoamines in the brain in comparison with orally administered Desvenlafaxine. Nose to brain delivery of Desvenlafaxine PLGA-chitosan nanoparticles also enhanced the pharmacokinetic profile of Desvenlafaxine in brain together with their brain/blood ratio at different time points. Thus, intranasal mucoadhesive Desvenlafaxine PLGA-chitosan nanoparticles could be potentially used for the treatment of depression.

  3. Targeted Delivery of Glucan Particle Encapsulated Gallium Nanoparticles Inhibits HIV Growth in Human Macrophages

    Directory of Open Access Journals (Sweden)

    Ernesto R. Soto

    2016-01-01

    Full Text Available Glucan particles (GPs are hollow, porous 3–5 μm microspheres derived from the cell walls of Baker’s yeast (Saccharomyces cerevisiae. The 1,3-β-glucan outer shell provides for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors. GPs have been used for macrophage-targeted delivery of a wide range of payloads (DNA, siRNA, protein, small molecules, and nanoparticles encapsulated inside the hollow GPs or bound to the surface of chemically derivatized GPs. Gallium nanoparticles have been proposed as an inhibitory agent against HIV infection. Here, macrophage targeting of gallium using GPs provides for more efficient delivery of gallium and inhibition of HIV infection in macrophages compared to free gallium nanoparticles.

  4. Intracellular antioxidants dissolve man-made antioxidant nanoparticles: using redox vulnerability of nanoceria to develop a responsive drug delivery system.

    Science.gov (United States)

    Muhammad, Faheem; Wang, Aifei; Qi, Wenxiu; Zhang, Shixing; Zhu, Guangshan

    2014-01-01

    Regeneratable antioxidant property of nanoceria has widely been explored to minimize the deleterious influences of reactive oxygen species. Limited information is, however, available regarding the biological interactions and subsequent fate of nanoceria in body fluids. This study demonstrates a surprising dissolution of stable and ultrasmall (4 nm) cerium oxide nanoparticles (CeO2 NPs) in response to biologically prevalent antioxidant molecules (glutathione, vitamin C). Such a redox sensitive behavior of CeO2 NPs is subsequently exploited to design a redox responsive drug delivery system for transporting anticancer drug (camptothecin). Upon exposing the CeO2 capped and drug loaded nanoconstruct to vitamin c or glutathione, dissolution-accompanied aggregation of CeO2 nanolids unleashes the drug molecules from porous silica to achieve a significant anticancer activity. Besides stimuli responsive drug delivery, immobilization of nanoceria onto the surface of mesoporous silica also facilitates us to gain a basic insight into the biotransformation of CeO2 in physiological mediums.

  5. Standardization of Nanoparticle Characterization: Methods for Testing Properties, Stability, and Functionality of Edible Nanoparticles.

    Science.gov (United States)

    McClements, Jake; McClements, David Julian

    2016-06-10

    There has been a rapid increase in the fabrication of various kinds of edible nanoparticles for oral delivery of bioactive agents, such as those constructed from proteins, carbohydrates, lipids, and/or minerals. It is currently difficult to compare the relative advantages and disadvantages of different kinds of nanoparticle-based delivery systems because researchers use different analytical instruments and protocols to characterize them. In this paper, we briefly review the various analytical methods available for characterizing the properties of edible nanoparticles, such as composition, morphology, size, charge, physical state, and stability. This information is then used to propose a number of standardized protocols for characterizing nanoparticle properties, for evaluating their stability to environmental stresses, and for predicting their biological fate. Implementation of these protocols would facilitate comparison of the performance of nanoparticles under standardized conditions, which would facilitate the rational selection of nanoparticle-based delivery systems for different applications in the food, health care, and pharmaceutical industries.

  6. Biomanufacturing and self-propulsion dynamics of nanoscale bacteria-enabled autonomous delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Traore, Mahama A.; Behkam, Bahareh, E-mail: behkam@vt.edu [Mechanical Engineering Department, Virginia Tech, Blacksburg, Virginia 24061 (United States); School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia 24061 (United States); Damico, Carmen M. [Mechanical Engineering Department, Virginia Tech, Blacksburg, Virginia 24061 (United States)

    2014-10-27

    Flagellated bacteria have superb self-propulsion capabilities and are able to effectively move through highly viscous fluid and semi-solid (porous) environments. This innate aptitude has been harvested for whole-cell actuation of bio-hybrid microrobotic systems with applications in directed transport and microassembly. In this work, we present the biomanufacturing of Nanoscale Bacteria-Enabled Autonomous Delivery Systems (NanoBEADS) by controlled self-assembly and investigate the role of nanoparticle load on the dynamics of their self-propulsion in aqueous environments. Each NanoBEADS agent is comprised of spherical polystyrene nanoparticles assembled onto the body of a flagellated Escherichia coli bacterium. We demonstrate that the NanoBEADS assembly configuration is strongly dependent upon the nanoparticles to bacteria ratio. Furthermore, we characterized the stochastic motion of the NanoBEADS as a function of the quantity and size of the nanoparticle load and computationally analyzed the effect of the nanoparticle load on the experienced drag force. We report that the average NanoBEADS swimming speed is reduced to 65% of the free-swimming bacteria speed (31 μm/s) at the highest possible load. NanoBEADS can be utilized as single agents or in a collaborative swarm in order to carry out specific tasks in a wide range of applications ranging from drug delivery to whole cell biosensing.

  7. Fabrication of Reductive-Responsive Prodrug Nanoparticles with Superior Structural Stability by Polymerization-Induced Self-Assembly and Functional Nanoscopic Platform for Drug Delivery.

    Science.gov (United States)

    Zhang, Wen-Jian; Hong, Chun-Yan; Pan, Cai-Yuan

    2016-09-12

    A highly efficient strategy, polymerization-induced self-assembly (PISA) for fabrication of the polymeric drug delivery systems in cancer chemotherapy is reported. Diblock prodrug copolymer, PEG-b-P(MEO2MA-co-CPTM) was used as the macro-RAFT agent to fabricate prodrug nanoparticles through PISA. The advantages of fabricating intelligent drug delivery system via this approach are as following: (1) Simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation in one-pot at relatively high concentration (100 mg/mL); (2) Almost complete monomer conversion allows direct application of the resultant prodrug nanoparticles without further purification; (3) Robust structures of the resultant prodrug nanoparticles, because the cross-linker was used as the comonomer, resulted in core-cross-linking simultaneously with the formation of the prodrug nanoparticles; (4) The drug content in the resultant prodrug nanoparticles can be accurately modulated just via adjusting the feed molar ratio of MEO2MA/CPTM in the synthesis of PEG-b-P(MEO2MA-co-CPTM). The prodrug nanoparticles with similar diameters but various drug contents were obtained using different prodrug macro-CTA. In consideration of the long-term biological toxicity, the prodrug nanoparticles with higher drug content exhibit more excellent anticancer efficiency due to that lower dosage of them are enough for effectively killing HeLa cells.

  8. Distribution and Biological Effects of Nanoparticles in the Reproductive System.

    Science.gov (United States)

    Liu, Ying; Li, Hongxia; Xiao, Kai

    2016-01-01

    Nanoparticles have shown great potential in biomedical applications such as imaging probes and drug delivery. However, the increasing use of nanoparticles has raised concerns about their adverse effects on human health and environment. Reproductive tissues and gametes represent highly delicate biological systems with the essential function of transmitting genetic information to the offspring, which is highly sensitive to environmental toxicants. This review aims to summarzie the penetration of physiological barriers (blood-testis barrier and placental barrier), distribution and biological effects of nanoparticles in the reproductive system, which is essential to control the beneficial effects of nanoparticles applications and to avoid their adverse effects on the reproductive system. We referred to a large number of relevant peer-reviewed research articles about the reproductive toxicity of nanoparticles. The comprehensive information was summarized into two parts: physiological barrier penetration and biological effects of nanoparticles in male or female reproductive system; distribution and metabolism of nanoparticles in the reproductive system. The representative examples were also presented in four tables. The in vitro and in vivo studies imply that some nanoparticles are able to cross the blood-testis barrier or placental barrier, and their penetration depends on the physicochemical characteristics of nanoparticles (e.g., composition, shape, particle size and surface coating). The toxicity assays indicate that nanoparticles might induce adverse physiological effects and impede fertility or embryogenesis. The barrier penetration, adverse physiological effects, distribution and metabolism are closely related to physicochemical characteristics of nanoparticles. Further systematic and mechanistic studies using well-characterized nanoparticles, relevant administration routes, and doses relevant to the expected exposure level are required to improve our

  9. Sonochemically synthesized biocompatible zirconium phosphate nanoparticles for pH sensitive drug delivery application.

    Science.gov (United States)

    Kalita, Himani; Prashanth Kumar, B N; Konar, Suraj; Tantubay, Sangeeta; Kr Mahto, Madhusudan; Mandal, Mahitosh; Pathak, Amita

    2016-03-01

    The present work reports the synthesis of biocompatible zirconium phosphate (ZP) nanoparticles as nanocarrier for drug delivery application. The ZP nanoparticles were synthesized via a simple sonochemical method in the presence of cetyltrimethylammonium bromide and their efficacy for the delivery of drugs has been tested through various in-vitro experiments. The particle size and BET surface area of the nanoparticles were found to be ~48 nm and 206.51 m(2)/g respectively. The conventional MTT assay and cellular localization studies of the particles, performed on MDA-MB-231 cell lines, demonstrate their excellent biocompatibility and cellular internalization behavior. The loading of curcumin, an antitumor drug, onto the ZP nanoparticles shows the rapid drug uptake ability of the particles, while the drug release study, performed at two different pH values (at 7.4 and 5) depicts pH sensitive release-profile. The MTT assay and cellular localization studies revealed higher cellular inhibition and better bioavailability of the nanoformulated curcumin compared to free curcumin. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Improvement of different vaccine delivery systems for cancer therapy

    Directory of Open Access Journals (Sweden)

    Safaiyan Shima

    2011-01-01

    Full Text Available Abstract Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.

  11. Surface engineering of macrophages with nanoparticles to generate a cell-nanoparticle hybrid vehicle for hypoxia-targeted drug delivery.

    Science.gov (United States)

    Holden, Christopher A; Yuan, Quan; Yeudall, W Andrew; Lebman, Deborah A; Yang, Hu

    2010-02-02

    Tumors frequently contain hypoxic regions that result from a shortage of oxygen due to poorly organized tumor vasculature. Cancer cells in these areas are resistant to radiation- and chemotherapy, limiting the treatment efficacy. Macrophages have inherent hypoxia-targeting ability and hold great advantages for targeted delivery of anticancer therapeutics to cancer cells in hypoxic areas. However, most anticancer drugs cannot be directly loaded into macrophages because of their toxicity. In this work, we designed a novel drug delivery vehicle by hybridizing macrophages with nanoparticles through cell surface modification. Nanoparticles immobilized on the cell surface provide numerous new sites for anticancer drug loading, hence potentially minimizing the toxic effect of anticancer drugs on the viability and hypoxia-targeting ability of the macrophage vehicles. In particular, quantum dots and 5-(aminoacetamido) fluorescein-labeled polyamidoamine dendrimer G4.5, both of which were coated with amine-derivatized polyethylene glycol, were immobilized to the sodium periodate-treated surface of RAW264.7 macrophages through a transient Schiff base linkage. Further, a reducing agent, sodium cyanoborohydride, was applied to reduce Schiff bases to stable secondary amine linkages. The distribution of nanoparticles on the cell surface was confirmed by fluorescence imaging, and it was found to be dependent on the stability of the linkages coupling nanoparticles to the cell surface.

  12. Use of fractional laser microablation and ultrasound to facilitate the delivery of gold nanoparticles into skin in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Terentyuk, G S; Genina, Elina A; Bashkatov, A N; Ryzhova, M V; Tsyganova, N A; Chumakov, D S; Khlebtsov, B N; Sazonov, A A; Dolotov, L E; Tuchin, Valerii V; Khlebtsov, Nikolai G; Inozemtseva, O A

    2012-06-30

    The delivery of gold nanoparticles (nanocages coated with a layer of silicon dioxide (40/20 nm)) dispersed in the solution (glycerol + polyethylene glycol-400, 1 : 1) into the skin tissue is studied experimentally in vivo. From the data of optical coherence tomography and histochemical analysis it follows that simple application of suspension of nanoparticles is not efficient enough for delivery of the particles into the skin as a result of passive diffusion. It is shown that fractional laser microablation of skin before the application of the suspension, followed by the topical treatment by ultrasound allows penetration through the epidermis layer and delivery of nanoparticles into dermis and hypodermis.

  13. Use of fractional laser microablation and ultrasound to facilitate the delivery of gold nanoparticles into skin in vivo

    International Nuclear Information System (INIS)

    Terentyuk, G S; Genina, Elina A; Bashkatov, A N; Ryzhova, M V; Tsyganova, N A; Chumakov, D S; Khlebtsov, B N; Sazonov, A A; Dolotov, L E; Tuchin, Valerii V; Khlebtsov, Nikolai G; Inozemtseva, O A

    2012-01-01

    The delivery of gold nanoparticles (nanocages coated with a layer of silicon dioxide (40/20 nm)) dispersed in the solution (glycerol + polyethylene glycol-400, 1 : 1) into the skin tissue is studied experimentally in vivo. From the data of optical coherence tomography and histochemical analysis it follows that simple application of suspension of nanoparticles is not efficient enough for delivery of the particles into the skin as a result of passive diffusion. It is shown that fractional laser microablation of skin before the application of the suspension, followed by the topical treatment by ultrasound allows penetration through the epidermis layer and delivery of nanoparticles into dermis and hypodermis.

  14. Use of fractional laser microablation and ultrasound to facilitate the delivery of gold nanoparticles into skin in vivo

    Science.gov (United States)

    Terentyuk, G. S.; Genina, Elina A.; Bashkatov, A. N.; Ryzhova, M. V.; Tsyganova, N. A.; Chumakov, D. S.; Khlebtsov, B. N.; Sazonov, A. A.; Dolotov, L. E.; Tuchin, Valerii V.; Khlebtsov, Nikolai G.; Inozemtseva, O. A.

    2012-06-01

    The delivery of gold nanoparticles (nanocages coated with a layer of silicon dioxide (40/20 nm)) dispersed in the solution (glycerol + polyethylene glycol-400, 1 : 1) into the skin tissue is studied experimentally in vivo. From the data of optical coherence tomography and histochemical analysis it follows that simple application of suspension of nanoparticles is not efficient enough for delivery of the particles into the skin as a result of passive diffusion. It is shown that fractional laser microablation of skin before the application of the suspension, followed by the topical treatment by ultrasound allows penetration through the epidermis layer and delivery of nanoparticles into dermis and hypodermis

  15. Nanostructured lipid carriers system: recent advances in drug delivery.

    Science.gov (United States)

    Iqbal, Md Asif; Md, Shadab; Sahni, Jasjeet Kaur; Baboota, Sanjula; Dang, Shweta; Ali, Javed

    2012-12-01

    Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.

  16. Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems.

    Science.gov (United States)

    Dalmoro, Annalisa; Bochicchio, Sabrina; Nasibullin, Shamil F; Bertoncin, Paolo; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I

    2018-05-17

    Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity. Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods. The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin. Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable

  17. Screening of siRNA nanoparticles for delivery to airway epithelial cells using high-content analysis

    LENUS (Irish Health Repository)

    Hibbitts, Alan

    2011-08-01

    Aims: Delivery of siRNA to the lungs via inhalation offers a unique opportunity to develop a new treatment paradigm for a range of respiratory conditions. However, progress has been greatly hindered by safety and delivery issues. This study developed a high-throughput method for screening novel nanotechnologies for pulmonary siRNA delivery. Methodology: Following physicochemical analysis, the ability of PEI–PEG–siRNA nanoparticles to facilitate siRNA delivery was determined using high-content analysis (HCA) in Calu-3 cells. Results obtained from HCA were validated using confocal microscopy. Finally, cytotoxicity of the PEI–PEG–siRNA particles was analyzed by HCA using the Cellomics® multiparameter cytotoxicity assay. Conclusion: PEI–PEG–siRNA nanoparticles facilitated increased siRNA uptake and luciferase knockdown in Calu-3 cells compared with PEI–siRNA.

  18. Sonochemically synthesized biocompatible zirconium phosphate nanoparticles for pH sensitive drug delivery application

    Energy Technology Data Exchange (ETDEWEB)

    Kalita, Himani, E-mail: hkalita74@gmail.com [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Prashanth Kumar, B.N., E-mail: prasanthkumar999@gmail.com [School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Konar, Suraj, E-mail: suraj.konar@gmail.com [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Tantubay, Sangeeta, E-mail: sang.chem2@gmail.com [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Mahto, Madhusudan Kr., E-mail: mahtomk0@gmail.com [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Mandal, Mahitosh, E-mail: mahitosh@smst.iitkgp.ernet.in [School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Pathak, Amita, E-mail: ami@chem.iitkgp.ernet.in [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India)

    2016-03-01

    The present work reports the synthesis of biocompatible zirconium phosphate (ZP) nanoparticles as nanocarrier for drug delivery application. The ZP nanoparticles were synthesized via a simple sonochemical method in the presence of cetyltrimethylammonium bromide and their efficacy for the delivery of drugs has been tested through various in-vitro experiments. The particle size and BET surface area of the nanoparticles were found to be ~ 48 nm and 206.51 m{sup 2}/g respectively. The conventional MTT assay and cellular localization studies of the particles, performed on MDA-MB-231 cell lines, demonstrate their excellent biocompatibility and cellular internalization behavior. The loading of curcumin, an antitumor drug, onto the ZP nanoparticles shows the rapid drug uptake ability of the particles, while the drug release study, performed at two different pH values (at 7.4 and 5) depicts pH sensitive release-profile. The MTT assay and cellular localization studies revealed higher cellular inhibition and better bioavailability of the nanoformulated curcumin compared to free curcumin. - Highlights: • Biocompatible zirconium phosphate nanoparticles were synthesized by a simple sonochemical approach. • Curcumin was rapidly loaded onto the particles by the aid by hydrogen bond formation. • The curcumin loaded zirconium phosphate nanoparticles depict pH triggered drug release phenomenon. • The nanoformulated curcumin showed enhanced anti-tumor activity as compared to the native curcumin.

  19. Sonochemically synthesized biocompatible zirconium phosphate nanoparticles for pH sensitive drug delivery application

    International Nuclear Information System (INIS)

    Kalita, Himani; Prashanth Kumar, B.N.; Konar, Suraj; Tantubay, Sangeeta; Mahto, Madhusudan Kr.; Mandal, Mahitosh; Pathak, Amita

    2016-01-01

    The present work reports the synthesis of biocompatible zirconium phosphate (ZP) nanoparticles as nanocarrier for drug delivery application. The ZP nanoparticles were synthesized via a simple sonochemical method in the presence of cetyltrimethylammonium bromide and their efficacy for the delivery of drugs has been tested through various in-vitro experiments. The particle size and BET surface area of the nanoparticles were found to be ~ 48 nm and 206.51 m"2/g respectively. The conventional MTT assay and cellular localization studies of the particles, performed on MDA-MB-231 cell lines, demonstrate their excellent biocompatibility and cellular internalization behavior. The loading of curcumin, an antitumor drug, onto the ZP nanoparticles shows the rapid drug uptake ability of the particles, while the drug release study, performed at two different pH values (at 7.4 and 5) depicts pH sensitive release-profile. The MTT assay and cellular localization studies revealed higher cellular inhibition and better bioavailability of the nanoformulated curcumin compared to free curcumin. - Highlights: • Biocompatible zirconium phosphate nanoparticles were synthesized by a simple sonochemical approach. • Curcumin was rapidly loaded onto the particles by the aid by hydrogen bond formation. • The curcumin loaded zirconium phosphate nanoparticles depict pH triggered drug release phenomenon. • The nanoformulated curcumin showed enhanced anti-tumor activity as compared to the native curcumin.

  20. A novel nanoparticulate system for sustained delivery of acid-labile lansoprazole.

    Science.gov (United States)

    Alai, Milind Sadashiv; Lin, Wen Jen

    2013-11-01

    In the present study, an effort was made to develop the Eudragit RS100 based nanoparticulate system for sustained delivery of an acid-labile drug, lansoprazole (LPZ). LPZ-loaded Eudragit RS100 nanoparticles (ERSNPs) were prepared by oil-in-water emulsion-solvent evaporation method. The effects of various formulation variables such as polymer concentration, drug amount and solvent composition on physicochemical performance of nanoparticles and in vitro drug release were investigated. All nanoparticles were spherical with particle size 198.9 ± 8.6-376.9 ± 5.6 nm and zeta potential +35.1 ± 1.7 to +40.2 ± 0.8 mV. The yield of nanoparticles was unaffected by change of these three variables. However, the drug loading and encapsulation efficiency were affected by polymer concentration and drug amount. On the other hand, the particle size of nanoparticles was significantly affected by polymer concentration and internal phase composition due to influence of droplet size during emulsification process. All nanoparticles prolonged drug release for 24h which was dominated by a combination of drug diffusion and polymer chain relaxation. The fastest and the slowest release rates were observed in C2-1002-10/0 and C8-4001-10/0, respectively, based on the release rate constant (k). Thus, the developed nanoparticles possessed a potential as a nano-carrier to sustain drug delivery for treatment of acid related disorders. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Hyaluronic acid/Chitosan nanoparticles as delivery vehicles for VEGF and PDGF-BB.

    Science.gov (United States)

    Parajó, Yolanda; D'Angelo, Ivana; Welle, Alexander; Garcia-Fuentes, Marcos; Alonso, María José

    2010-11-01

    The development of a vascular network in tissue-engineered constructs is a fundamental bottleneck of bioregenerative medicine, particularly when the size of the implant exceeds a certain limit given by diffusion lengths and/or if the host tissue shows a very active metabolism. One of the approaches to achieve the vascularization of tissue constructs is generating a sustained release of proangiogenic factors from the ischemic site. This work describes the formation and characterization of hyaluronic acid-chitosan (HA/CS) nanoparticles for the delivery of two pro-angiogenic growth factors: vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF-BB). These nanoparticles were prepared by an ionic gelification technique, and different formulations were developed by encapsulating the growth factors in association with two stabilizing agents: bovine serum albumin or heparin sodium salt. These carriers were characterized with regard to their physicochemical properties, their stability in biological media, and their cytotoxicity in the C3a hepatoma cell line. The results show that nanoparticles around 200 nm can be prepared by this method. HA/CS nanoparticles were stable when incubated in EMEM cell culture medium or in water at 37°C for 24 h. Cell culture tests confirmed that HA/CS nanoparticles are not cytotoxic within the concentration range used for growth factor delivery. Moreover, HA/CS nanoparticles were able to entrap efficiently both growth factors, reaching association values of 94% and 54% for VEGF and PDGF, respectively. In vitro release studies confirm that PDGF-BB is released from HA/CS nanoparticles in a sustained manner over approximately 1 week. On the other hand, VEGF is completely released within the first 24 h.

  2. Carrier-Based Drug Delivery System for Treatment of Acne

    Science.gov (United States)

    Vyas, Amber; Kumar Sonker, Avinesh

    2014-01-01

    Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system. PMID:24688376

  3. Synthesis and characterization of modified starch/polybutadiene as novel transdermal drug delivery system.

    Science.gov (United States)

    Saboktakin, Mohammad Reza; Akhyari, Shahab; Nasirov, Fizuli A

    2014-08-01

    Transdermal drug delivery systems are topically administered medicaments in the form of patches that deliver drugs for systemic effects at a predetermined and controlled rate. It works very simply in which drug is applied inside the patch and it is worn on skin for long period of time. Polymer matrix, drug, permeation enhancers are the main components of transdermal drug delivery systems. The objective of the present study was to develop the modified starch and 1,4-cis polybutadiene nanoparticles as novel polymer matrix system. We have been studied the properties of a novel transdermal drug delivery system with clonidine as drug model. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Bioreducible Lipid-like Nanoparticles for Intracellular Protein Delivery

    Science.gov (United States)

    Arellano, Carlos Luis

    Protein-based therapy is one of the most direct ways to manipulate cell function and treat human disease. Although protein therapeutics has made its way to clinical practice, with five of the top fifteen global pharmaceuticals being peptide or protein-based drugs, one common limitation is that the effects of protein therapy are only achieved through the targeting of cell surface receptors and intracellular domains. Due to the impermeability of the cell membrane to most foreign materials, entire classes of potentially therapeutic proteins cannot thoroughly be studied without a safe and efficient method of transporting proteins into the cytosol. We report the use of a combinatorially-designed bioreducible lipid-like material (termed "lipidoid") - based protein delivery platform for the transfection of human cancer cell lines. Lipidoid nanoparticles are synthesized through a thin film dispersion method. The degradation of the bioreducible nanoparticles was observed when exposed to glutathione, a highly reductive compound present in the cytosol. We demonstrate that the nanoparticles are capable of transfecting a dose-dependent concentration of our model protein, beta-galactosidase into HeLa cells. Furthermore, formulations of the lipidoid containing the cytotoxic proteins saporin and RNase-A are both capable of inhibiting tumor cell proliferation as observed in in vitro treatment of different human cancer cell lines. There was no observed loss in protein activity after lyophilization and long--term storage, indicating the potential of pre-clinical applications. Overall, we demonstrate an effective approach to protein formulation and intracellular delivery. We believe that our formulations will lead to the study of a whole class of previously untapped therapeutics that may generate new solutions for previously untreatable diseases.

  5. The effect of particle shape on cellular interaction and drug delivery applications of micro- and nanoparticles.

    Science.gov (United States)

    Jindal, Anil B

    2017-10-30

    Encapsulation of therapeutic agents in nanoparticles offers several benefits including improved bioavailability, site specific delivery, reduced toxicity and in vivo stability of proteins and nucleotides over conventional delivery options. These benefits are consequence of distinct in vivo pharmacokinetic and biodistribution profile of nanoparticles, which is dictated by the complex interplay of size, surface charge and surface hydrophobicity. Recently, particle shape has been identified as a new physical parameter which has exerted tremendous impact on cellular uptake and biodistribution, thereby in vivo performance of nanoparticles. Improved therapeutic efficacy of anticancer agents using non-spherical particles is the recent development in the field. Additionally, immunological response of nanoparticles was also altered when antigens were loaded in non-spherical nanovehicles. The apparent impact of particle shape inspired the new research in the field of drug delivery. The present review therefore details the research in this field. The review focuses on methods of fabrication of particles of non-spherical geometries and impact of particle shape on cellular uptake, biodistribution, tumor targeting and production of immunological responses. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Inhibition of Xenograft tumor growth by gold nanoparticle-DNA oligonucleotide conjugates-assisted delivery of BAX mRNA.

    Directory of Open Access Journals (Sweden)

    Ji-Hyun Yeom

    Full Text Available Use of non-biological agents for mRNA delivery into living systems in order to induce heterologous expression of functional proteins may provide more advantages than the use of DNA and/or biological vectors for delivery. However, the low efficiency of mRNA delivery into live animals, using non-biological systems, has hampered the use of mRNA as a therapeutic molecule. Here, we show that gold nanoparticle-DNA oligonucleotide (AuNP-DNA conjugates can serve as universal vehicles for more efficient delivery of mRNA into human cells, as well as into xenograft tumors generated in mice. Injections of BAX mRNA loaded on AuNP-DNA conjugates into xenograft tumors resulted in highly efficient mRNA delivery. The delivered mRNA directed the efficient production of biologically functional BAX protein, a pro-apoptotic factor, consequently inhibiting tumor growth. These results demonstrate that mRNA delivery by AuNP-DNA conjugates can serve as a new platform for the development of safe and efficient gene therapy.

  7. An amphiphilic graft copolymer-based nanoparticle platform for reduction-responsive anticancer and antimalarial drug delivery

    Science.gov (United States)

    Najer, Adrian; Wu, Dalin; Nussbaumer, Martin G.; Schwertz, Geoffrey; Schwab, Anatol; Witschel, Matthias C.; Schäfer, Anja; Diederich, François; Rottmann, Matthias; Palivan, Cornelia G.; Beck, Hans-Peter; Meier, Wolfgang

    2016-08-01

    Medical applications of anticancer and antimalarial drugs often suffer from low aqueous solubility, high systemic toxicity, and metabolic instability. Smart nanocarrier-based drug delivery systems provide means of solving these problems at once. Herein, we present such a smart nanoparticle platform based on self-assembled, reduction-responsive amphiphilic graft copolymers, which were successfully synthesized through thiol-disulfide exchange reaction between thiolated hydrophilic block and pyridyl disulfide functionalized hydrophobic block. These amphiphilic graft copolymers self-assembled into nanoparticles with mean diameters of about 30-50 nm and readily incorporated hydrophobic guest molecules. Fluorescence correlation spectroscopy (FCS) was used to study nanoparticle stability and triggered release of a model compound in detail. Long-term colloidal stability and model compound retention within the nanoparticles was found when analyzed in cell media at body temperature. In contrast, rapid, complete reduction-triggered disassembly and model compound release was achieved within a physiological reducing environment. The synthesized copolymers revealed no intrinsic cellular toxicity up to 1 mg mL-1. Drug-loaded reduction-sensitive nanoparticles delivered a hydrophobic model anticancer drug (doxorubicin, DOX) to cancer cells (HeLa cells) and an experimental, metabolically unstable antimalarial drug (the serine hydroxymethyltransferase (SHMT) inhibitor (+/-)-1) to Plasmodium falciparum-infected red blood cells (iRBCs), with higher efficacy compared to similar, non-sensitive drug-loaded nanoparticles. These responsive copolymer-based nanoparticles represent a promising candidate as smart nanocarrier platform for various drugs to be applied to different diseases, due to the biocompatibility and biodegradability of the hydrophobic block, and the protein-repellent hydrophilic block.Medical applications of anticancer and antimalarial drugs often suffer from low aqueous

  8. A novel delivery vector for targeted delivery of the antiangiogenic drug paclitaxel to angiogenic blood vessels: TLTYTWS-conjugated PEG–PLA nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Fei, E-mail: tanfeivip@126.com; Mo, Xiao-hui, E-mail: 675382206@qq.com [Shanghai Skin Disease Hospital (China); Zhao, Jian, E-mail: 22459402@qq.com [Karolinska University Hospital Solna, Department of Oncology-Pathology, Karolinska Institutet, CCK (Sweden); Liang, Hui, E-mail: nanotan@126.com [People' s Hospital of Longhua New District Shenzhen, Department of urology (China); Chen, Zhong-jian, E-mail: pfjk927627702@126.com; Wang, Xiu-li, E-mail: tanfeit@126.com [Shanghai Skin Disease Hospital (China)

    2017-02-15

    Antiangiogenesis has been widely accepted as an attractive strategy to combat tumor growth, invasion, and metastasis. An actively targeting nanoparticle-based drug delivery system (nano-DDS) would provide an alternative method to achieve antiangiogenic antitumor therapy. In the present study, our group fabricated novel nano-DDS, TLTYTWS (TS) peptide-modified poly(ethylene glycol)–poly(lactic acid) (PEG–PLA) nanoparticles (TS-NPs) encapsulating a drug with antiangiogenic potential, paclitaxel (Ptx) (TS-Ptx-NPs). The nanoparticles were uniformly spherical and had a unimodal particle size distribution and slightly negative zeta potential. TS-NPs accumulated significantly in human umbilical vein endothelial cells (HUVECs) via energy-dependent and caveolae- and lipid raft-mediated endocytosis and improved the antiproliferative, antimigratory, and antitube-forming abilities of paclitaxel in vitro. Following intravenous administration, TS-Ptx-NPs presented favorable pharmacokinetic profiles. Melanoma distribution assays confirmed that TS-NPs achieved higher accumulation and penetration at melanoma sites. These results collectively indicated that TLTYTWS-decorated nanoparticles can be considered to be a promising nano-DDS for chemotherapies targeting tumor angiogenesis and have great potential to improve the efficacy of antiangiogenic therapy in melanoma tumor-bearing nude mice.

  9. A novel delivery vector for targeted delivery of the antiangiogenic drug paclitaxel to angiogenic blood vessels: TLTYTWS-conjugated PEG–PLA nanoparticles

    International Nuclear Information System (INIS)

    Tan, Fei; Mo, Xiao-hui; Zhao, Jian; Liang, Hui; Chen, Zhong-jian; Wang, Xiu-li

    2017-01-01

    Antiangiogenesis has been widely accepted as an attractive strategy to combat tumor growth, invasion, and metastasis. An actively targeting nanoparticle-based drug delivery system (nano-DDS) would provide an alternative method to achieve antiangiogenic antitumor therapy. In the present study, our group fabricated novel nano-DDS, TLTYTWS (TS) peptide-modified poly(ethylene glycol)–poly(lactic acid) (PEG–PLA) nanoparticles (TS-NPs) encapsulating a drug with antiangiogenic potential, paclitaxel (Ptx) (TS-Ptx-NPs). The nanoparticles were uniformly spherical and had a unimodal particle size distribution and slightly negative zeta potential. TS-NPs accumulated significantly in human umbilical vein endothelial cells (HUVECs) via energy-dependent and caveolae- and lipid raft-mediated endocytosis and improved the antiproliferative, antimigratory, and antitube-forming abilities of paclitaxel in vitro. Following intravenous administration, TS-Ptx-NPs presented favorable pharmacokinetic profiles. Melanoma distribution assays confirmed that TS-NPs achieved higher accumulation and penetration at melanoma sites. These results collectively indicated that TLTYTWS-decorated nanoparticles can be considered to be a promising nano-DDS for chemotherapies targeting tumor angiogenesis and have great potential to improve the efficacy of antiangiogenic therapy in melanoma tumor-bearing nude mice.

  10. A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system

    Science.gov (United States)

    Wang, Shaowei; Wei, Xiaochun; Sun, Xiaojuan; Chen, Chongwei; Zhou, Jingming; Zhang, Ge; Wu, Heng; Guo, Baosheng

    2018-01-01

    Background Cartilage degeneration affects millions of people but preventing its degeneration is a big challenge. Although RNA interference (RNAi) has been used in human trials via silencing specific genes, the cartilage RNAi has not been possible to date because the cartilage is an avascular and very dense tissue with very low permeability. Purpose The objective of this study was to develop and validate a novel lipid nanoparticle (LNP)-siRNA delivery system that can prevent cartilage degeneration by knocking down specific genes. Methods LNP transfection efficiency was evaluated in vitro and ex vivo. Indian Hedgehog (Ihh) has been correlated with cartilage degeneration. The in vivo effects of LNP-Ihh siRNA complexes on cartilage degeneration were evaluated in a rat model of surgery-induced osteoarthritis (OA). Results In vitro, 100% of chondrocytes were transfected with siRNA in the LNP-siRNA group. In accordance with the cell culture results, red positive signals could be detected even in the deep layer of cartilage tissue cultures treated by LNP-beacon. In vivo data showed that LNP is specific for cartilage, since positive signals were detected by fluorescence molecular tomography and confocal microscopy in joint cartilage injected with LNP-beacon, but not on the surface of the synovium. In the rat model of OA, intraarticular injection of LNP-Ihh siRNA attenuated OA progression, and PCR results showed LNP-Ihh siRNA exerted a positive impact on anabolic metabolism and negative impact on catabolic metabolism. Conclusion This study demonstrates that our LNP-RNAi delivery system has a significantly chondroprotective effect that attenuates cartilage degeneration and holds great promise as a powerful tool for treatment of cartilage diseases by knocking down specific genes. PMID:29440889

  11. Chitosan-based nanoparticles for survivin targeted siRNA delivery in breast tumor therapy and preventing its metastasis.

    Science.gov (United States)

    Sun, Ping; Huang, Wei; Jin, Mingji; Wang, Qiming; Fan, Bo; Kang, Lin; Gao, Zhonggao

    Nanoparticle-mediated small interfering RNA (siRNA) delivery is a promising therapeutic strategy in various cancers. However, it is difficult to deliver degradative siRNA to tumor tissue, and thus a safe and efficient vector for siRNA delivery is essential for cancer therapy. In this study, poly(ethylene glycol)-modified chitosan (PEG-CS) was synthesized successfully for delivering nucleic acid drug. We deemed that PEGylated CS could improve its solubility by forming a stable siRNA loaded in nanoparticles, and enhancing transfection efficiency of siRNA-loaded CS nanoparticles in cancer cell line. The research results showed that siRNA loaded in PEGylated CS (PEG-CS/siRNA) nanoparticles with smaller particle size had superior structural stability in the physical environment compared to CS nanoparticles. The data of in vitro antitumor activity revealed that 4T1 tumor cell growth was significantly inhibited and cellular uptake of PEG-CS/siRNA nanoparticles in 4T1 cells was dramatically enhanced compared to naked siRNA groups. The results from flow cytometry and confocal laser scanning microscopy showed that PEG-CS/siRNA nanoparticles were more easily taken up than naked siRNA. Importantly, PEG-CS/siRNA nanoparticles significantly reduced the growth of xenograft tumors of 4T1 cells in vivo. It has been demonstrated that the PEG-CS is a safe and efficient vector for siRNA delivery, and it can effectively reduce tumor growth and prevent metastasis.

  12. Intranasal Delivery of pGDNF Nanoparticles for Parkinson's Disease

    Science.gov (United States)

    Harmon, Brendan Trevor

    Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects the dopaminergic A9 nigrostriatal tract. For dopamine neurons specifically, glial cell-derived neurotrophic factor (GDNF) has been shown to promote their survival and proliferation both in culture and in vivo. GDNF has also proven to be neuroprotective and restorative in various animal models of PD and some human clinical trials. However, its delivery to the brain has required invasive surgical routes which are not clinically practical for many patients. The main objective of this project was to test intranasal delivery to the brain of a nanoparticle vector incorporating an expression plasmid for GDNF (pGDNF). The intranasal route circumvents the blood-brain barrier, allowing larger sized vectors into the central nervous system while avoiding peripheral distribution. This approach would provide a renewable source of GDNF within the target areas of the brain, the striatum and the substantia nigra (SN) without the need for surgical injections or frequent re-dosing. A PEGylated polylysine compacted plasmid nanoparticle vector (PEG-CK30), developed by Copernicus Therapeutics, Inc., has been shown to transfect neurons and glial cells in vivo while lacking the safety issues present with other vectors. The first goal of this work was to determine if these PEG-CK30 compacted plasmid nanoparticles can successfully transfect cells and express the reporter protein, enhanced green fluorescent protein (eGFP) in the rat brain after intranasal administration. Initial in vivo experiments utilized the expression plasmid pCG, expressing eGFP under the fast-acting cytomegalovirus (CMV) promoter. Intranasal administration of pCG nanoparticles resulted in evidence of transfection of brain cells, as shown both qualitatively, by GFP-immunohistochemistry, and quantitatively, by GFP-ELISA. Expression was detected throughout the rat brain two days post-administration. Following the proof

  13. Microemulsions based transdermal drug delivery systems.

    Science.gov (United States)

    Vadlamudi, Harini C; Narendran, Hyndavi; Nagaswaram, Tejeswari; Yaga, Gowri; Thanniru, Jyotsna; Yalavarthi, Prasanna R

    2014-01-01

    Since the discovery of microemulsions by Jack H Schulman, there has been huge progress made in applying microemulsion systems in plethora of research and industrial process. Microemulsions are optically isotropic systems consisting of water, oil and amphiphile. These systems are beneficial due to their thermodynamic stability, optical clarity, ease of preparation, higher diffusion and absorption rates. Moreover, it has been reported that the ingredients of microemulsion can effectively overcome the diffusion barrier and penetrate through the stratum corneum of the skin. Hence it becomes promising for both transdermal and dermal drug delivery. However, low viscosity of microemulsion restrains its applicability in pharmaceutical industry. To overcome the above drawback, the low viscous microemulsions were added to viscous gel bases to potentiate its applications as topical drug delivery systems so that various drug related toxic effects and erratic drug absorption can be avoided. The present review deals with the microemulsions, various techniques involved in the development of organic nanoparticles. The review emphasized on microemulsion based systems such as hydrogels and organogels. The physicochemical characteristics, mechanical properties, rheological and stability principles involved in microemulsion based viscous gels were also explored.

  14. The impact of nanobiotechnology on the development of new drug delivery systems

    NARCIS (Netherlands)

    Kayser, Oliver; Lemke, A.; Hernandez-Trejo, N.

    2005-01-01

    Nanotechnology, or systems/devices manufactured at the molecular level, is a multidisciplinary scientific field undergoing explosive development. A part of this field is the development of nanoscaled drug delivery devices. Nanoparticles have been developed as an important strategy to deliver

  15. Contact-facilitated drug delivery with Sn2 lipase labile prodrugs optimize targeted lipid nanoparticle drug delivery.

    Science.gov (United States)

    Pan, Dipanjan; Pham, Christine T N; Weilbaecher, Katherine N; Tomasson, Michael H; Wickline, Samuel A; Lanza, Gregory M

    2016-01-01

    Sn2 lipase labile phospholipid prodrugs in conjunction with contact-facilitated drug delivery offer an important advancement in Nanomedicine. Many drugs incorporated into nanosystems, targeted or not, are substantially lost during circulation to the target. However, favorably altering the pharmacokinetics and volume of distribution of systemic drug delivery can offer greater efficacy with lower toxicity, leading to new prolonged-release nanoexcipients. However, the concept of achieving Paul Erhlich's inspired vision of a 'magic bullet' to treat disease has been largely unrealized due to unstable nanomedicines, nanosystems achieving low drug delivery to target cells, poor intracellular bioavailability of endocytosed nanoparticle payloads, and the substantial biological barriers of extravascular particle penetration into pathological sites. As shown here, Sn2 phospholipid prodrugs in conjunction with contact-facilitated drug delivery prevent premature drug diffusional loss during circulation and increase target cell bioavailability. The Sn2 phospholipid prodrug approach applies equally well for vascular constrained lipid-encapsulated particles and micelles the size of proteins that penetrate through naturally fenestrated endothelium in the bone marrow or thin-walled venules of an inflamed microcirculation. At one time Nanomedicine was considered a 'Grail Quest' by its loyal opposition and even many in the field adsorbing the pains of a long-learning curve about human biology and particles. However, Nanomedicine with innovations like Sn2 phospholipid prodrugs has finally made 'made the turn' toward meaningful translational success. © 2015 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals, Inc.

  16. Zein nanoparticles as delivery systems for covalently linked and physically entrapped folic acid

    Energy Technology Data Exchange (ETDEWEB)

    Chuacharoen, Thanida [Suan Sunandha Rajabhat University, Faculty of Science and Technology (Thailand); Sabliov, Cristina M., E-mail: CSabliov@agcenter.lsu.edu [Louisiana State University and LSU AgCenter, Department of Biological and Agricultural Engineering (United States)

    2017-02-15

    Zein nanoparticles covalently linked to folic acid were hypothesized to sustain the release of the folic acid in addition to targeting cancer cells overexpressing folate-binding receptors, whereas zein nanoparticles with physically entrapped folic acid would only be able to control the release of the bioactive without targeting of cancer cells. The two types of particles, folic acid covalently linked zein nanoparticles (ZN-FA nps) and zein nanoparticles with entrapped folic acid (ZN(FA) nps), were synthesized and the covalent link between folic acid and zein was assessed by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ({sup 1}H NMR). Their size, polydispersity index, zeta potential, morphology, and loading capacity were evaluated by dynamic light scattering (DLS), transmission electron microscopy (TEM), and spectrophotometric technique. The release studies of the folic acid preformed in phosphate-buffered saline (PBS) at 37 °C for 7 days concluded that the release of the loaded folic acid was sustained over 7 days for both systems. The cytotoxicity was investigated using a methyl thiazolyl tetrazolium (MTT) assay, and the results showed that zein nanoparticles were biocompatible to HeLa (an overexpressing folate receptor cells) and A549 (a deficient folate receptor cells) cells, which have different levels of folate receptors on surface and both folic acid nanoparticle systems were able to diminish the adverse toxic effect of folic acid to cells. The increased uptake of ZN-FA nps relative to ZN(FA) nps supported the use of ZN-FA nps as targeting nanoagents to cells overexpressing folate receptors.

  17. Zein nanoparticles as delivery systems for covalently linked and physically entrapped folic acid

    Science.gov (United States)

    Chuacharoen, Thanida; Sabliov, Cristina M.

    2017-02-01

    Zein nanoparticles covalently linked to folic acid were hypothesized to sustain the release of the folic acid in addition to targeting cancer cells overexpressing folate-binding receptors, whereas zein nanoparticles with physically entrapped folic acid would only be able to control the release of the bioactive without targeting of cancer cells. The two types of particles, folic acid covalently linked zein nanoparticles (ZN-FA nps) and zein nanoparticles with entrapped folic acid (ZN(FA) nps), were synthesized and the covalent link between folic acid and zein was assessed by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (1H NMR). Their size, polydispersity index, zeta potential, morphology, and loading capacity were evaluated by dynamic light scattering (DLS), transmission electron microscopy (TEM), and spectrophotometric technique. The release studies of the folic acid preformed in phosphate-buffered saline (PBS) at 37 °C for 7 days concluded that the release of the loaded folic acid was sustained over 7 days for both systems. The cytotoxicity was investigated using a methyl thiazolyl tetrazolium (MTT) assay, and the results showed that zein nanoparticles were biocompatible to HeLa (an overexpressing folate receptor cells) and A549 (a deficient folate receptor cells) cells, which have different levels of folate receptors on surface and both folic acid nanoparticle systems were able to diminish the adverse toxic effect of folic acid to cells. The increased uptake of ZN-FA nps relative to ZN(FA) nps supported the use of ZN-FA nps as targeting nanoagents to cells overexpressing folate receptors.

  18. Zein nanoparticles as delivery systems for covalently linked and physically entrapped folic acid

    International Nuclear Information System (INIS)

    Chuacharoen, Thanida; Sabliov, Cristina M.

    2017-01-01

    Zein nanoparticles covalently linked to folic acid were hypothesized to sustain the release of the folic acid in addition to targeting cancer cells overexpressing folate-binding receptors, whereas zein nanoparticles with physically entrapped folic acid would only be able to control the release of the bioactive without targeting of cancer cells. The two types of particles, folic acid covalently linked zein nanoparticles (ZN-FA nps) and zein nanoparticles with entrapped folic acid (ZN(FA) nps), were synthesized and the covalent link between folic acid and zein was assessed by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ("1H NMR). Their size, polydispersity index, zeta potential, morphology, and loading capacity were evaluated by dynamic light scattering (DLS), transmission electron microscopy (TEM), and spectrophotometric technique. The release studies of the folic acid preformed in phosphate-buffered saline (PBS) at 37 °C for 7 days concluded that the release of the loaded folic acid was sustained over 7 days for both systems. The cytotoxicity was investigated using a methyl thiazolyl tetrazolium (MTT) assay, and the results showed that zein nanoparticles were biocompatible to HeLa (an overexpressing folate receptor cells) and A549 (a deficient folate receptor cells) cells, which have different levels of folate receptors on surface and both folic acid nanoparticle systems were able to diminish the adverse toxic effect of folic acid to cells. The increased uptake of ZN-FA nps relative to ZN(FA) nps supported the use of ZN-FA nps as targeting nanoagents to cells overexpressing folate receptors.

  19. Molecular design and nanoparticle-mediated intracellular delivery of functional proteins to target cellular pathways

    Science.gov (United States)

    Shah, Dhiral Ashwin

    functional proteins can be delivered intracellularly in vitro using nanoparticles and used to target key signaling proteins and regulate cell signaling pathways. The same concept of naturally occurring protein-protein interactions can also be implemented to selectively bring intracellular protein targets in close proximity to proteasomal degradation machinery in cells and effect their depletion from the cellular compartments. This approach will be able to not only target entire pool of proteins to ubiquitination-mediated degradation, but also to specific sub-pools of posttranslationally modified proteins in the cell, provided peptides having distinct binding affinities are identified for posttranslational modifications. This system can then be tested for intracellular protein delivery using nanoparticle carriers to identify roles of different posttranslational modifications on the protein's activity. In future work, we propose to develop a cellular detection system, based on GFP complementation, which can be used to evaluate the efficiency of different protein delivery carriers to internalize proteins into the cell cytosol. We envision the application of nanoscale materials as intracellular protein delivery vehicles to target diverse cell signaling pathways at the posttranslational level, and subsequent metabolic manipulation, which may have interesting therapeutic properties and can potentially target stem cell fate.

  20. Nanoparticles and direct immunosuppression

    Science.gov (United States)

    Ngobili, Terrika A

    2016-01-01

    Targeting the immune system with nanomaterials is an intensely active area of research. Specifically, the capability to induce immunosuppression is a promising complement for drug delivery and regenerative medicine therapies. Many novel strategies for immunosuppression rely on nanoparticles as delivery vehicles for small-molecule immunosuppressive compounds. As a consequence, efforts in understanding the mechanisms in which nanoparticles directly interact with the immune system have been overshadowed. The immunological activity of nanoparticles is dependent on the physiochemical properties of the nanoparticles and its subsequent cellular internalization. As the underlying factors for these reactions are elucidated, more nanoparticles may be engineered and evaluated for inducing immunosuppression and complementing immunosuppressive drugs. This review will briefly summarize the state-of-the-art and developments in understanding how nanoparticles induce immunosuppressive responses, compare the inherent properties of nanomaterials which induce these immunological reactions, and comment on the potential for using nanomaterials to modulate and control the immune system. PMID:27229901

  1. pH-Switch Nanoprecipitation of Polymeric Nanoparticles for Multimodal Cancer Targeting and Intracellular Triggered Delivery of Doxorubicin.

    Science.gov (United States)

    Herranz-Blanco, Bárbara; Shahbazi, Mohammad-Ali; Correia, Alexandra R; Balasubramanian, Vimalkumar; Kohout, Tomáš; Hirvonen, Jouni; Santos, Hélder A

    2016-08-01

    Theranostic nanoparticles are emerging as potent tools for noninvasive diagnosis, treatment, and monitoring of solid tumors. Herein, an advanced targeted and multistimuli responsive theranostic platform is presented for the intracellular triggered delivery of doxorubicin. The system consists of a polymeric-drug conjugate solid nanoparticle containing encapsulated superparamagnetic iron oxide nanoparticles (IO@PNP) and decorated with a tumor homing peptide, iRGD. The production of this nanosystem is based on a pH-switch nanoprecipitation method in organic-free solvents, making it ideal for biomedical applications. The nanosystem shows sufficient magnetization saturation for magnetically guided therapy along with reduced cytotoxicity and hemolytic effects. IO@PNP are largely internalized by endothelial and metastatic cancer cells and iRGD decorated IO@PNP moderately enhance their internalization into endothelial cells, while no enhancement is found for the metastatic cancer cells. Poly(ethylene glycol)-block-poly(histidine) with pH-responsive and proton-sponge properties promotes prompt lysosomal escape once the nanoparticles are endocyted. In addition, the polymer-doxorubicin conjugate solid nanoparticles show both intracellular lysosomal escape and efficient translocation of doxorubicin to the nuclei of the cells via cleavage of the amide bond. Overall, IO@PNP-doxorubicin and the iRGD decorated counterpart demonstrate to enhance the toxicity of doxorubicin in cancer cells by improving the intracellular delivery of the drug carried in the IO@PNP. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Preparation of Emulsifying Wax/GMO Nanoparticles and Evaluation as a Delivery System for Repurposing Simvastatin in Bone Regeneration.

    Science.gov (United States)

    Eskinazi-Budge, Aaron; Manickavasagam, Dharani; Czech, Tori; Novak, Kimberly; Kunzler, James; Oyewumi, Moses O

    2018-05-30

    Simvastatin (Sim) is a widely known drug in the treatment of hyperlipidemia that has attracted so much attention in bone regeneration based on its potential osteoanabolic effect. However, repurposing of Sim in bone regeneration will require suitable delivery systems that can negate undesirable off-target/side effects. In this study, we have investigated a new lipid nanoparticle (NP) platform that was fabricated using a binary blend of emulsifying wax (Ewax) and glyceryl monooleate (GMO). Using the binary matrix materials, NPs loaded with Sim (0-500 µg/mL) were prepared and showed an average particle size of about 150 nm. NP size stability was dependent on Sim concentration loaded in NPs. The suitability of NPs prepared with the binary matrix materials in Sim delivery for potential application in bone regeneration was supported by biocompatibility in pre-osteoclastic and pre-osteoblastic cells. Additional data demonstrated that biofunctional Sim was released from NPs that facilitated differentiation of osteoblasts (cells that form bones) while inhibiting differentiation of osteoclasts (cells that resorb bones). The overall work demonstrated the preparation of NPs from Ewax/GMO blends and characterization to ascertain potential suitability in Sim delivery for bone regeneration. Additional studies on osteoblast and osteoclast functions are warranted to fully evaluate the efficacy simvastatin-loaded Ewax/GMO NPs using in-vitro and in-vivo approaches.

  3. Solubility enhancement and delivery systems of curcumin a herbal medicine: a review.

    Science.gov (United States)

    Hani, Umme; Shivakumar, H G

    2014-01-01

    Curcumin diferuloylmethane is a main yellow bioactive component of turmeric, possess wide spectrum of biological actions. It was found to have anti-inflammatory, antioxidant, anticarcinogenic, antimutagenic, anticoagulant, antifertility, antidiabetic, antibacterial, antifungal, antiprotozoal, antiviral, antifibrotic, antivenom, antiulcer, hypotensive and hypocholesteremic activities. However, the benefits are curtailed by its extremely poor aqueous solubility, which subsequently limits the bioavailability and therapeutic effects of curcumin. Nanotechnology is the available approach in solving these issues. Therapeutic efficacy of curcumin can be utilized effectively by doing improvement in formulation properties or delivery systems. Numerous attempts have been made to design a delivery system of curcumin. Currently, nanosuspensions, micelles, nanoparticles, nano-emulsions, etc. are used to improve the in vitro dissolution velocity and in vivo efficiency of curcumin. This review focuses on the methods to increase solubility of curcumin and various nanotechnologies based delivery systems and other delivery systems of curcumin.

  4. Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations

    Directory of Open Access Journals (Sweden)

    Özcan İ

    2013-01-01

    Full Text Available İpek Özcan, Erkan Azizoğlu, Taner Şenyiğit, Mine Özyazıcı, Özgen ÖzerEge University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Bornova, Izmir, TurkeyAbstract: The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%, were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01% was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders.Keywords: skin permeation, anti-inflammatory activity, skin blanching, TEWL

  5. Thiolated Eudragit nanoparticles for oral insulin delivery: preparation, characterization and in vivo evaluation.

    Science.gov (United States)

    Zhang, Yan; Wu, Xiaorong; Meng, Lingkuo; Zhang, Yu; Ai, Ruiting; Qi, Na; He, Haibing; Xu, Hui; Tang, Xing

    2012-10-15

    In the present study thiolated Eudragit L100 (Eul) based polymeric nanoparticles (NPs) were employed to develop an oral insulin delivery system. Sulfydryl modification was achieved by grafting cysteine to the carboxylic acid group of Eudragit L100, which displayed maximum conjugate level of 390.3±13.4 μmol thiol groups per gram. Eudragit L100-cysteine (Eul-cys) and Eul nanoparticles were prepared by the precipitation method, in which reversible swelling of pH-sensitive material was used for insulin loading and release. Nanoparticles were characterized in terms of their particle size, morphology, loading efficiency (LE%) and in vitro insulin release behavior. The NPs had an average size of 324.2±39.0 nm and 308.8±35.7 nm, maximal LE% of 92.2±1.7% and 96.4±0.5% for Eul-cys and Eul, respectively. The release profile of NPs in vitro showed pH-dependent behavior. Circular dichroism (CD) spectroscopy analysis proved that the secondary structure of the insulin released from NPs was unchanged compared with native insulin. The mucoadhesion study in vitro showed that Eul-cys NPs produced a 3-fold and 2.8-fold increase in rat jejunum and ileum compared with unmodified polymer NPs, respectively, which was due to the immobilization of thiol groups on Eudragit L100. Oral administration of insulin-loaded Eul-cys NPs produced a higher and prolonged hypoglycemic action, and the corresponding relative bioavailability of insulin was found to be 7.33±0.33%, an increase of 2.8-fold compared with Eul NPs (2.65±0.63%). This delivery system is a promising novel tool to improve the absorption of protein and peptide drugs in the intestinal tract. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Self-assembled liquid crystalline nanoparticles as a novel ophthalmic delivery system for dexamethasone: Improving preocular retention and ocular bioavailability.

    Science.gov (United States)

    Gan, Li; Han, Shun; Shen, Jinqiu; Zhu, Jiabi; Zhu, Chunliu; Zhang, Xinxin; Gan, Yong

    2010-08-30

    The object of this study was to design novel self-assembled liquid crystalline nanoparticles (cubosomes) as an ophthalmic delivery system for dexamethasone (DEX) to improve its preocular retention and ocular bioavailability. DEX cubosome particles were produced by fragmenting a cubic crystalline phase of monoolein and water in the presence of stabilizer Poloxamer 407. Small angle X-ray diffraction (SAXR) profiles revealed its internal structure as Pn3m space group, indicating the diamond cubic phase. In vitro, the apparent permeability coefficient of DEX administered in cubosomes exhibited a 4.5-fold (F1) and 3.5-fold (F2) increase compared to that of Dex-Na phosphate eye drops. Preocular retention studies revealed that the retention of cubosomes was significantly longer than that of solution and carbopol gel, with AUC(0-->180min) of Rh B cubosomes being 2-3-fold higher than that of the other two formulations. In vivo pharmacokinetics in aqueous humor was evaluated by microdialysis, which indicated a 1.8-fold (F1) increase in AUC(0-->240min) of DEX administered in cubosomes relative to that of Dex-Na phosphate eye drops, with about an 8-fold increase compared to that of DEX suspension. Corneal cross-sections after incubation with DEX cubosomes demonstrated an unaffected corneal structure and tissue integrity, which indicated the good biocompatibility of DEX cubosomes. In conclusion, self-assembled liquid crystalline nanoparticles might represent a promising vehicle for effective ocular drug delivery. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

  7. Controlled delivery of acyclovir from porous silicon micro- and nanoparticles

    Science.gov (United States)

    Maniya, Nalin H.; Patel, Sanjaykumar R.; Murthy, Z. V. P.

    2015-03-01

    In this work, micro- and nanoparticles of porous silicon (PSi) are demonstrated to act as effective carrier for the controlled delivery of acyclovir (ACV). PSi films prepared by electrochemical etching were fractured by ultrasonication to prepare micro- and nanoparticles. PSi native particles were thermally oxidized (TOPSi) and thermally hydrosilylated using undecylenic acid (UnPSi). PSi particles with three different surface chemistries were then loaded with ACV by physical adsorption and covalent attachment. Such particles were characterized by scanning electron microscopy, dynamic light scattering, and Fourier transform infrared spectroscopy. In vitro ACV release experiments in phosphate buffered saline showed sustained release behaviour from both micro- and nanoparticles and order of release was found to be native PSi > TOPSi > UnPSi. Drug release kinetics study using Korsmeyer-Peppas model suggested a combination of both drug diffusion and Si scaffold erosion based drug release mechanisms.

  8. Neutrophil targeted nano-drug delivery system for chronic obstructive lung diseases.

    Science.gov (United States)

    Vij, Neeraj; Min, Taehong; Bodas, Manish; Gorde, Aakruti; Roy, Indrajit

    2016-11-01

    The success of drug delivery to target airway cell(s) remains a significant challenge due to the limited ability of nanoparticle (NP) systems to circumvent protective airway-defense mechanisms. The size, density, surface and physical-chemical properties of nanoparticles are the key features that determine their ability to navigate across the airway-barrier. We evaluated here the efficacy of a PEGylated immuno-conjugated PLGA-nanoparticle (PINP) to overcome this challenge and selectively deliver drug to specific inflammatory cells (neutrophils). We first characterized the size, shape, surface-properties and neutrophil targeting using dynamic laser scattering, transmission electron microscopy and flow cytometry. Next, we assessed the efficacy of neutrophil-targeted PINPs in transporting through the airway followed by specific binding and release of drug to neutrophils. Finally, our results demonstrate the efficacy of PINP mediated non-steroidal anti-inflammatory drug-(ibuprofen) delivery to neutrophils in murine models of obstructive lung diseases, based on its ability to control neutrophilic-inflammation and resulting lung disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. AND logic-like pH- and light-dual controlled drug delivery by surface modified mesoporous silica nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Junwei; He, Zhaoshuai; Li, Biao; Cheng, Tanyu, E-mail: tycheng@shnu.edu.cn; Liu, Guohua

    2017-04-01

    Recently, the controlled drug delivery system has become a potential platform for biomedical application. Herein, we developed a pH and light-dual controlled cargo release system exhibiting AND logic based on MCM-41 mesoporous silica nanoparticles, which was surface modified using β-cyclodextrin (β-CD) with imine bond and azobenzene derivative. The complex of β-CD and azobenzene derivative effectively blocked the cargo delivery in pH = 7.0 phosphate buffered saline (PBS) solution without 365 nm UV light irradiation. The cargo was fully released when both factors of acidic environment (pH = 5.0 PBS) and 365 nm UV light irradiation were satisfied, meanwhile only very little cargo was delivered if one factor was satisfied. The result also demonstrates that the opening/closing of the gate and the release of the cargo in small portions can be controlled. - Highlights: • A pH and light-dual controlled cargo release system exhibiting AND logic is developed. • The delivery system can release the cargo in small potions by controlling the opening/closing of the gate. • The delivery system realizes the controlled release in zebrafish.

  10. The effect of nanoparticle size on theranostic systems: the optimal particle size for imaging is not necessarily optimal for drug delivery

    Science.gov (United States)

    Dreifuss, Tamar; Betzer, Oshra; Barnoy, Eran; Motiei, Menachem; Popovtzer, Rachela

    2018-02-01

    Theranostics is an emerging field, defined as combination of therapeutic and diagnostic capabilities in the same material. Nanoparticles are considered as an efficient platform for theranostics, particularly in cancer treatment, as they offer substantial advantages over both common imaging contrast agents and chemotherapeutic drugs. However, the development of theranostic nanoplatforms raises an important question: Is the optimal particle for imaging also optimal for therapy? Are the specific parameters required for maximal drug delivery, similar to those required for imaging applications? Herein, we examined this issue by investigating the effect of nanoparticle size on tumor uptake and imaging. Anti-epidermal growth factor receptor (EGFR)-conjugated gold nanoparticles (GNPs) in different sizes (diameter range: 20-120 nm) were injected to tumor bearing mice and their uptake by tumors was measured, as well as their tumor visualization capabilities as tumor-targeted CT contrast agent. Interestingly, the results showed that different particles led to highest tumor uptake or highest contrast enhancement, meaning that the optimal particle size for drug delivery is not necessarily optimal for tumor imaging. These results have important implications on the design of theranostic nanoplatforms.

  11. pH-Sensitive nanoparticles as smart carriers for selective intracellular drug delivery to tumor.

    Science.gov (United States)

    Li, Xin-Xin; Chen, Jing; Shen, Jian-Min; Zhuang, Ran; Zhang, Shi-Qi; Zhu, Zi-Yun; Ma, Jing-Bo

    2018-05-05

    Herein, a smart pH-sensitive nanoparticle (DGL-PEG-Tat-KK-DMA-DOX) was prepared to achieve the selective intracellular drug delivery. In this nanoparticle, a PEG-grafted cell penetrating peptide (PEG-Tat-KK) was designed and acted as the cell penetrating segment. By introducing the pH-sensitive amide bonds between the peptide and blocking agent (2,3-dimethylmaleic anhydride, DMA), the controllable moiety (PEG-Tat-KK-DMA) endowed the nanoparticle with a charge-switchable shell and temporarily blocked penetrating function, thus improving the specific internalization. Besides, dendrigraft poly-L-lysine (DGL) used as the skeleton can greatly improve the drug loading because of the highly dendritic framework. Under the stimuli of acidic pH, this nanoparticle exhibited a remarkable charge-switchable property. The drug release showed an expected behavior with little release in the neutral pH media but relatively fast release in the acidic media. The in vitro experiments revealed that the cellular uptake and cytotoxicity were significantly enhanced after the pH was decreased. In vivo biodistribution and antitumor research indicated that the nanoparticle had noteworthy specificity and antitumor efficacy with a tumor inhibition rate of 79.7%. These results verified this nanoparticle could efficiently improve the selective intracellular delivery and possessed a great potential in tumor treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Methotrexate nanoparticle delivery system for treatment of ...

    African Journals Online (AJOL)

    Results: Nanoparticle size, zeta potential and encapsulation efficacy were 164.4 ± 6.9 nm, .... blood count, hemoglobin, C-reactive protein ... was attributable to a decrease in electrostatic ... interactions between the polymer and drug in this.

  13. Solid lipid nanoparticles mediate non-viral delivery of plasmid DNA to dendritic cells

    Science.gov (United States)

    Penumarthi, Alekhya; Parashar, Deepti; Abraham, Amanda N.; Dekiwadia, Chaitali; Macreadie, Ian; Shukla, Ravi; Smooker, Peter M.

    2017-06-01

    There is an increasing demand for novel DNA vaccine delivery systems, mainly for the non-viral type as they are considered relatively safe. Therefore, solid lipid nanoparticles (SLNs) were investigated for their suitability as a non-viral DNA vaccine delivery system. SLNs were synthesised by a modified solvent-emulsification method in order to study their potential to conjugate with plasmid DNA and deliver them in vitro to dendritic cells using eGFP as the reporter plasmid. The DNA-SLN complexes were characterised by electron microscopy, gel retardation assays and dynamic light scattering. The cytotoxicity assay data supported their biocompatibility and was used to estimate safe threshold concentration resulting in high transfection rate. The transfection efficiency of these complexes in a dendritic cell line was shown to increase significantly compared to plasmid alone, and was comparable to that mediated by lipofectamine. Transmission electron microscopy studies delineated the pathway of cellular uptake. Endosomal escape was observed supporting the mechanism of transfection.

  14. An Overview of Clinical and Commercial Impact of Drug Delivery Systems

    Science.gov (United States)

    Anselmo, Aaron C.; Mitragotri, Samir

    2014-01-01

    Drug delivery systems are widely researched and developed to improve the delivery of pharmaceutical compounds and molecules. The last few decades have seen a marked growth of the field fueled by increased number of researchers, research funding, venture capital and the number of start-ups. Collectively, the growth has led to novel systems that make use of micro/nano-particles, transdermal patches, inhalers, drug reservoir implants and antibody-drug conjugates. While the increased research activity is clearly an indication of proliferation of the field, clinical and commercial translation of early-stage research ideas is critically important for future growth and interest in the field. Here, we will highlight some of the examples of novel drug delivery systems that have undergone such translation. Specifically, we will discuss the developments, advantages, limitations and lessons learned from: (i) microparticle-based depot formulations, (ii) nanoparticle-based cancer drugs, (iii) transdermal systems, (iv) oral drug delivery systems, (v) pulmonary drug delivery, (vi) implants and (vii) antibody-drug conjugates. These systems have impacted treatment of many prevalent diseases including diabetes, cancer and cardiovascular diseases, among others. At the same time, these systems are integral and enabling components of products that collectively generate annual revenues exceeding US $100 billion. These examples provide strong evidence of the clinical and commercial impact of drug delivery systems. PMID:24747160

  15. One-step formation of lipid-polyacrylic acid-calcium carbonate nanoparticles for co-delivery of doxorubicin and curcumin.

    Science.gov (United States)

    Peng, Jianqing; Fumoto, Shintaro; Miyamoto, Hirotaka; Chen, Yi; Kuroda, Naotaka; Nishida, Koyo

    2017-09-01

    A doxorubicin (Dox) and curcumin (Cur) combination treatment regimen has been widely studied in pre-clinical research. However, the nanoparticles developed for this combination therapy require a consecutive drug loading process because of the different water-solubility of these drugs. This study provides a strategy for the "one-step" formation of nanoparticles encapsulating both Dox and Cur. We took advantage of polyacrylic acid (PAA) and calcium carbonate (CaCO 3 ) to realise a high drug entrapment efficiency (EE) and pH-sensitive drug release using a simplified preparation method. Optimisation of lipid ratios and concentrations of CaCO 3 was conducted. Under optimal conditions, the mean diameter of PEGylated lipid/PAA/CaCO 3 nanoparticles with encapsulated Cur and Dox (LPCCD) was less than 100 nm. An obvious pH-sensitive release of both drugs was observed, with different Dox and Cur release rates. Successful co-delivery of Cur and Dox was achieved via LPCCD on HepG2 cells. LPCCD altered the bio-distribution of Dox and Cur in vivo and decreased Dox-induced cardiotoxicity. The current investigation has developed an efficient ternary system for co-delivery of Dox and Cur to tumours, using a "one-step" formation resulting in nanoparticles possessing remarkable pH-sensitive drug release behaviour, which may be valuable for further clinical studies and eventual clinical application.

  16. Enhancing the transdermal delivery of rigid nanoparticles using the simultaneous application of ultrasound and sodium lauryl sulfate.

    Science.gov (United States)

    Lopez, Renata F V; Seto, Jennifer E; Blankschtein, Daniel; Langer, Robert

    2011-01-01

    The potential of rigid nanoparticles to serve as transdermal drug carriers can be greatly enhanced by improving their skin penetration. Therefore, the simultaneous application of ultrasound and sodium lauryl sulfate (referred to as US/SLS) was evaluated as a skin pre-treatment method for enhancing the passive transdermal delivery of nanoparticles. We utilized inductively coupled plasma mass spectrometry and an improved application of confocal microscopy to compare the delivery of 10- and 20-nm cationic, neutral, and anionic quantum dots (QDs) into US/SLS-treated and untreated pig split-thickness skin. Our findings include: (a) ∼0.01% of the QDs penetrate the dermis of untreated skin (which we quantify for the first time), (b) the QDs fully permeate US/SLS-treated skin, (c) the two cationic QDs studied exhibit different extents of skin penetration and dermal clearance, and (d) the QD skin penetration is heterogeneous. We discuss routes of nanoparticle skin penetration and the application of the methods described herein to address conflicting literature reports on nanoparticle skin penetration. We conclude that US/SLS treatment significantly enhances QD transdermal penetration by 500-1300%. Our findings suggest that an optimum surface charge exists for nanoparticle skin penetration, and motivate the application of nanoparticle carriers to US/SLS-treated skin for enhanced transdermal drug delivery. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Current directions in core-shell nanoparticle design

    Science.gov (United States)

    Schärtl, Wolfgang

    2010-06-01

    Ten years ago I wrote a review about the important field of core-shell nanoparticles, focussing mainly on our own work about tracer systems, and briefly addressing polymer-coated nanoparticles as fillers for homogeneous polymer-colloid composites. Since then, the potential use of core-shell nanoparticles as multifunctional sensors or potential smart drug-delivery vehicles in biology and medicine has gained more and more importance, affording special types of multi-functionalized and bio-compatible nanoparticles. In this new review article, I try to address the most important developments during the last ten years. This overview is mainly based on frequently cited and more specialized recent review articles from leaders in their respective field. We will consider a variety of nanoscopic core-shell architectures from highly fluorescent nanoparticles (NPs), protected magnetic NPs, multifunctional NPs, thermoresponsive NPs and biocompatible systems to, finally, smart drug-delivery systems.Ten years ago I wrote a review about the important field of core-shell nanoparticles, focussing mainly on our own work about tracer systems, and briefly addressing polymer-coated nanoparticles as fillers for homogeneous polymer-colloid composites. Since then, the potential use of core-shell nanoparticles as multifunctional sensors or potential smart drug-delivery vehicles in biology and medicine has gained more and more importance, affording special types of multi-functionalized and bio-compatible nanoparticles. In this new review article, I try to address the most important developments during the last ten years. This overview is mainly based on frequently cited and more specialized recent review articles from leaders in their respective field. We will consider a variety of nanoscopic core-shell architectures from highly fluorescent nanoparticles (NPs), protected magnetic NPs, multifunctional NPs, thermoresponsive NPs and biocompatible systems to, finally, smart drug-delivery systems

  18. Thermo-responsive human α-elastin self-assembled nanoparticles for protein delivery.

    Science.gov (United States)

    Kim, Jae Dong; Jung, Youn Jae; Woo, Chang Hee; Choi, Young Chan; Choi, Ji Suk; Cho, Yong Woo

    2017-01-01

    Self-assembled nanoparticles based on PEGylated human α-elastin were prepared as a potential vehicle for sustained protein delivery. The α-elastin was extracted from human adipose tissue and modified with methoxypolyethyleneglycol (mPEG) to control particle size and enhance the colloidal stability. The PEGylated human α-elastin showed sol-to-particle transition with a lower critical solution temperature (LCST) of 25°C-40°C in aqueous media. The PEGylated human α-elastin nanoparticles (PhENPs) showed a narrow size distribution with an average diameter of 330±33nm and were able to encapsulate significant amounts of insulin and bovine serum albumin (BSA) upon simple mixing at low temperature in water and subsequent heating to physiological temperature. The release profiles of insulin and BSA showed sustained release for 72h. Overall, the thermo-responsive self-assembled PhENPs provide a useful tool for a range of protein delivery and tissue engineering applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. PEGylated versus non-PEGylated magnetic nanoparticles as camptothecin delivery system

    Directory of Open Access Journals (Sweden)

    Paula M. Castillo

    2014-08-01

    Full Text Available Camptothecin (CPT; (S-(+-4-ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-(4H,12H-dione is a highly cytotoxic natural alkaloid that has not yet found use as chemotherapeutic agent due to its poor water-solubility and chemical instability and, as a consequence, no effective administration means have been designed. In this work, camptothecin has been successfully loaded into iron oxide superparamagnetic nanoparticles with an average size of 14 nm. It was found that surface modification of the nanoparticles by polyethylene glycol enables loading a large amount of camptothecin. While the unloaded nanoparticles do not induce apoptosis in the H460 lung cancer cell line, the camptothecin-loaded nanoparticle formulations exhibit remarkable pro-apoptotic activity. These results indicate that camptothecin retains its biological activity after loading onto the magnetic nanoparticles. The proposed materials represent novel materials based on naturally occurring bioactive molecules loaded onto nanoparticles to be used as chemotherapeutic formulations. The procedure seems apt to be extended to other active molecules extracted from natural products. In addition, these materials offer the potential of being further implemented for combined imaging and therapeutics, as magnetic nanoparticles are known to be multifunctional tools for biomedicine.

  20. pH-sensitive chitosan/alginate core-shell nanoparticles for efficient and safe oral insulin delivery.

    Science.gov (United States)

    Mukhopadhyay, Piyasi; Chakraborty, Souma; Bhattacharya, Sourav; Mishra, Roshnara; Kundu, P P

    2015-01-01

    Chitosan-alginate (CS/ALG) nanoparticles were prepared by formation of an ionotropic pre-gelation of an alginate (ALG) core entrapping insulin, followed by chitosan (CS) polyelectrolyte complexation, for successful oral insulin administration. Mild preparation process without harsh chemicals is aimed at improving insulin bio-efficiency in in vivo model. The nanoparticles showed an average particle size of 100-200 nm in dynamic light scattering (DLS), with almost spherical or sub-spherical shape and ∼ 85% of insulin encapsulation. Again, retention of almost entire amount of encapsulated insulin in simulated gastric buffer followed by its sustained release in simulated intestinal condition proved its pH sensitivity in in vitro release studies. Significant hypoglycemic effects with improved insulin-relative bioavailability (∼ 8.11%) in in vivo model revealed the efficacy of these core-shell nanoparticles of CS/ALG as an oral insulin carrier. No systemic toxicity was found after its peroral treatment, suggesting these core-shell nanoparticles as a promising device for potential oral insulin delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Ingenious pH-sensitive dextran/mesoporous silica nanoparticles based drug delivery systems for controlled intracellular drug release.

    Science.gov (United States)

    Zhang, Min; Liu, Jia; Kuang, Ying; Li, Qilin; Zheng, Di-Wei; Song, Qiongfang; Chen, Hui; Chen, Xueqin; Xu, Yanglin; Li, Cao; Jiang, Bingbing

    2017-05-01

    In this work, dextran, a polysaccharide with excellent biocompatibility, is applied as the "gatekeeper" to fabricate the pH-sensitive dextran/mesoporous silica nanoparticles (MSNs) based drug delivery systems for controlled intracellular drug release. Dextran encapsulating on the surface of MSNs is oxidized by NaIO 4 to obtain three kinds of dextran dialdehydes (PADs), which are then coupled with MSNs via pH-sensitive hydrazone bond to fabricate three kinds of drug carriers. At pH 7.4, PADs block the pores to prevent premature release of anti-cancer drug doxorubicin hydrochloride (DOX). However, in the weakly acidic intracellular environment (pH∼5.5) the hydrazone can be ruptured; and the drug can be released from the carriers. The drug loading capacity, entrapment efficiency and release rates of the drug carriers can be adjusted by the amount of NaIO 4 applied in the oxidation reaction. And from which DOX@MSN-NH-N=C-PAD 10 is chosen as the most satisfactory one for the further in vitro cytotoxicity studies and cellular uptake studies. The results demonstrate that DOX@MSN-NH-N=C-PAD 10 with an excellent pH-sensitivity can enter HeLa cells to release DOX intracellular due to the weakly acidic pH intracellular and kill the cells. In our opinion, the ingenious pH-sensitive drug delivery systems have application potentials for cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Development of amphiphilic gamma-PGA-nanoparticle based tumor vaccine: potential of the nanoparticulate cytosolic protein delivery carrier.

    Science.gov (United States)

    Yoshikawa, Tomoaki; Okada, Naoki; Oda, Atsushi; Matsuo, Kazuhiko; Matsuo, Keisuke; Mukai, Yohei; Yoshioka, Yasuo; Akagi, Takami; Akashi, Mitsuru; Nakagawa, Shinsaku

    2008-02-08

    Nanoscopic therapeutic systems that incorporate biomacromolecules, such as protein and peptides, are emerging as the next generation of nanomedicine aimed at improving the therapeutic efficacy of biomacromolecular drugs. In this study, we report that poly(gamma-glutamic acid)-based nanoparticles (gamma-PGA NPs) are excellent protein delivery carriers for tumor vaccines that delivered antigenic proteins to antigen-presenting cells and elicited potent immune responses. Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic proteins through cytosolic translocation from the endosomes, which is a key process of gamma-PGA NP-mediated anti-tumor immune responses. Our findings suggest that the gamma-PGA NP system is suitable for the intracellular delivery of protein-based drugs as well as tumor vaccines.

  3. Nanoparticles and the blood coagulation system. Part I: benefits of nanotechnology.

    Science.gov (United States)

    Ilinskaya, Anna N; Dobrovolskaia, Marina A

    2013-05-01

    Nanotechnology is proven to provide certain benefits in drug delivery by improving solubility, increasing uptake to target sites and changing pharmacokinetics profiles of traditional drugs. Since properties of many materials change tremendously at the nanoscale levels, nanotechnology is also being explored in various industrial applications. As such, nanoparticles are rapidly entering various areas of industry, biology and medicine. The benefits of using nanotechnology for industrial and biomedical applications are often tempered by concerns about the safety of these new materials. One such area of concern includes their effect on the immune system. While nanoparticle interactions with various constituents of the immune system have been reviewed before, little attention was given to nanoparticle effects on the blood coagulation system. Nanoparticle interface with the blood coagulation system may lead to either benefits to the host or adverse reactions. This article reviews recent advances in our understanding of nanoparticle interactions with plasma coagulation factors, platelets, endothelial cells and leukocytes. Part I is focused on desirable interactions between nanoparticles and the coagulation system, and discusses benefits of using nanotechnology to intervene in coagulation disorders. Undesirable interactions posing safety concerns are covered in part II, which will be published in the June issue of Nanomedicine.

  4. Brain-targeted delivery of trans-activating transcriptor-conjugated magnetic PLGA/lipid nanoparticles.

    Directory of Open Access Journals (Sweden)

    Xiangru Wen

    Full Text Available Magnetic poly (D,L-lactide-co-glycolide (PLGA/lipid nanoparticles (MPLs were fabricated from PLGA, L-α-phosphatidylethanolamine (DOPE, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-amino (polyethylene glycol (DSPE-PEG-NH2, and magnetic nanoparticles (NPs, and then conjugated to trans-activating transcriptor (TAT peptide. The TAT-MPLs were designed to target the brain by magnetic guidance and TAT conjugation. The drugs hesperidin (HES, naringin (NAR, and glutathione (GSH were encapsulated in MPLs with drug loading capacity (>10% and drug encapsulation efficiency (>90%. The therapeutic efficacy of the drug-loaded TAT-MPLs in bEnd.3 cells was compared with that of drug-loaded MPLs. The cells accumulated higher levels of TAT-MPLs than MPLs. In addition, the accumulation of QD-loaded fluorescein isothiocyanate (FITC-labeled TAT-MPLs in bEnd.3 cells was dose and time dependent. Our results show that TAT-conjugated MPLs may function as an effective drug delivery system that crosses the blood brain barrier to the brain.

  5. An effective intracellular delivery system of monoclonal antibody for treatment of tumors: erythrocyte membrane-coated self-associated antibody nanoparticles

    Science.gov (United States)

    Gao, Lipeng; Han, Lin; Ding, Xiaoling; Xu, Jiaojiao; Wang, Jing; Zhu, Jianzhong; Lu, Weiyue; Sun, Jihong; Yu, Lei; Yan, Zhiqiang; Wang, Yiting

    2017-08-01

    Antibody-based drugs have attracted much attention for their targeting ability, high efficacy and low toxicity. But it is difficult for those intrabodies, a kind of antibody whose targets are intracellular biomarkers, to become effective drugs due to the lack of intracellular delivery strategy and their short circulation time in blood. Human telomerase reverse transcriptase (hTERT), an important biomarker for tumors, is expressed only in cytoplasm instead of on cell membrane. In this study, the anti-hTERT blocking monoclonal antibody (mAb), as the model intrabody, was used to prepare nanoparticles (NPs), followed by the encapsulation of erythrocyte membrane (EM), to obtain the EM-coated anti-hTERT mAb NPs delivery system. The final NPs showed a z-average hydrodynamic diameter of about 197.3 nm. The in vitro cellular uptake by HeLa cells confirmed that compared with free anti-hTERT mAb, the EM-coated anti-hTERT mAb NPs exhibited a significantly increased uptake by tumor cells. Besides, the pharmacokinetic study confirmed that the EM encapsulation can remarkably prolong the circulation time and increase the area under curve (AUC) of NPs in blood. The EM-coated anti-hTERT mAb NPs exhibited a remarkably decreased uptake by macrophages than uncoated NPs, which may be responsible for the prolonged circulation time and increased AUC. Furthermore, the frozen section of tumor tissue was performed and proved that the EM-coated anti-hTERT mAb NPs can be more effectively accumulated in tumor tissues than the free mAb and uncoated NPs. In summary, this study indicated that EM-coated anti-hTERT mAb NPs are an effective delivery system for the long circulation and intracellular delivery of an intrabody, and make it possible for the intracellular biomarkers to become the potential targets of drugs.

  6. The magnetic graphene-based nanocomposite: An efficient anticancer delivery system

    Science.gov (United States)

    Jafarizad, Abbas; Jaymand, Mehdi; Taghizadehghalehjougi, Ali; Mohammadi-Nasr, Saeed; Jabbari, Amir Mohammad

    2018-01-01

    The aim of this study is the development of an efficient anticancer drug delivery nanosystem using PEGylated graphene oxide/magnetite nanoparticles (PEG-GO/Fe3O4). The nanosystem was loaded with mitoxantrone (MTX) as a universal anticancer drug. The cytotoxicity effect of the MTX-loaded GO-PEG/Fe3O4 nanocomposite was studied against U87 MG cell line using MTT cell viablity assay. The mechanism of action, the genes contributed in apoptosis (Casp 9, and Casp 3) and survival (BcL-2, BAX) have been investigated using quantitative real time-PCR. As the results of biological assays, controlled drug release behavior of the developed nanosystem as well as the inherent physicochemical and biological characteristics of both magnetit nanoparticles and graphene nanomaterials, we envision that the GO-PEG/Fe3O4 nanocomposite may be applied as enhanced drug delivery system for various cancer therapies (e.g., brain cancer) using both chemo- and photothermal therapy methods.

  7. Magnetic lipid nanoparticles loading doxorubicin for intracellular delivery: Preparation and characteristics

    International Nuclear Information System (INIS)

    Ying Xiaoying; Du Yongzhong; Hong Linghong; Yuan Hong; Hu Fuqiang

    2011-01-01

    Tumor intracellular delivery is an effective route for targeting chemotherapy to enhance the curative effect and minimize the side effect of a drug. In this study, the magnetic lipid nanoparticles with an uptake ability by tumor cells were prepared dispersing ferroso-ferric oxide nanoparticles in aqueous phase using oleic acid (OA) as a dispersant, and following the solvent dispersion of lipid organic solution. The obtained nanoparticles with 200 nm volume average diameter and -30 mV surface zeta potential could be completely removed by external magnetic field from aqueous solution. Using doxorubicin (DOX) as a model drug, the drug-loaded magnetic lipid nanoparticles were investigated in detail, such as the effects of OA, drug and lipid content on volume average diameter, zeta potential, drug encapsulation efficiency, drug loading, and in vitro drug release. The drug loading capacity and encapsulation efficiency were enhanced with increasing drug or lipid content, reduced with increasing OA content. The in vitro drug release could be controlled by changing drug or lipid content. Cellular uptake by MCF-7 cells experiment presented the excellent internalization ability of the prepared magnetic lipid nanoparticles. These results evidenced that the present magnetic lipid nanoparticles have potential for targeting therapy of antitumor drugs. - Research highlights: → A simple solvent diffusion method was developed to prepare magnetic lipid nanoparticles. → The doxorubicin-loaded magnetic lipid nanoparticles could be controlled by preparation recipe. → Magnetic lipid nanoparticles had internalization ability into tumor cells.

  8. Controlled delivery of acyclovir from porous silicon micro- and nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Maniya, Nalin H.; Patel, Sanjaykumar R.; Murthy, Z.V.P., E-mail: zvpm2000@yahoo.com

    2015-03-01

    Graphical abstract: - Highlights: • Porous silicon (PSi) was fabricated by electrochemical etching process. • Micro- and nanoparticles were prepared by ultrasonic fracture of PSi films. • Acyclovir was loaded into native, oxidized, and hydrosilylated PSi particles. • Micro- and nanoparticles displays controlled release behaviour for several days. • Drug release behaviour and release kinetics from PSi particles were studied. - Abstract: In this work, micro- and nanoparticles of porous silicon (PSi) are demonstrated to act as effective carrier for the controlled delivery of acyclovir (ACV). PSi films prepared by electrochemical etching were fractured by ultrasonication to prepare micro- and nanoparticles. PSi native particles were thermally oxidized (TOPSi) and thermally hydrosilylated using undecylenic acid (UnPSi). PSi particles with three different surface chemistries were then loaded with ACV by physical adsorption and covalent attachment. Such particles were characterized by scanning electron microscopy, dynamic light scattering, and Fourier transform infrared spectroscopy. In vitro ACV release experiments in phosphate buffered saline showed sustained release behaviour from both micro- and nanoparticles and order of release was found to be native PSi > TOPSi > UnPSi. Drug release kinetics study using Korsmeyer-Peppas model suggested a combination of both drug diffusion and Si scaffold erosion based drug release mechanisms.

  9. Controlled delivery of acyclovir from porous silicon micro- and nanoparticles

    International Nuclear Information System (INIS)

    Maniya, Nalin H.; Patel, Sanjaykumar R.; Murthy, Z.V.P.

    2015-01-01

    Graphical abstract: - Highlights: • Porous silicon (PSi) was fabricated by electrochemical etching process. • Micro- and nanoparticles were prepared by ultrasonic fracture of PSi films. • Acyclovir was loaded into native, oxidized, and hydrosilylated PSi particles. • Micro- and nanoparticles displays controlled release behaviour for several days. • Drug release behaviour and release kinetics from PSi particles were studied. - Abstract: In this work, micro- and nanoparticles of porous silicon (PSi) are demonstrated to act as effective carrier for the controlled delivery of acyclovir (ACV). PSi films prepared by electrochemical etching were fractured by ultrasonication to prepare micro- and nanoparticles. PSi native particles were thermally oxidized (TOPSi) and thermally hydrosilylated using undecylenic acid (UnPSi). PSi particles with three different surface chemistries were then loaded with ACV by physical adsorption and covalent attachment. Such particles were characterized by scanning electron microscopy, dynamic light scattering, and Fourier transform infrared spectroscopy. In vitro ACV release experiments in phosphate buffered saline showed sustained release behaviour from both micro- and nanoparticles and order of release was found to be native PSi > TOPSi > UnPSi. Drug release kinetics study using Korsmeyer-Peppas model suggested a combination of both drug diffusion and Si scaffold erosion based drug release mechanisms

  10. [Study on liver targeted drug delivery system of the effective anticancer component from Bolbstemma paniculatum].

    Science.gov (United States)

    Sun, Yi-Yi; Ll, Tong-Hui; Tang, Chen-Kang; Zhu, Zi-Ping; Chi, Qun; Hou, Shi-Xiang

    2005-06-01

    To study the liver targeted drug delivery system of TBMS--the effective anticancer component from Bolbstemma paniculatum, and to discuss the system's function of decreasing toxicity. BCA was used as carrier material. The preparation through overall feedback dynamic techniques. The properties of preparation and toxicology were also technology of nanoparticles was optimized studied. Thenanoparticles' targeting in mice vivo was observed with transmission electron microscopy. The function of decreasing toxicity was researched by the XXTX-2000 automatic quantitative analysis management system. D50 was 0.68 microm. Drug-loading rate and entrapment rate were 37.3% and 88.6% respectively. The release in vitro accorded with Weibull equation. The reaching release balance time and the t 1/2 extended 26 times and 19 times respectively comparing with injection. Nanoparticles mainly distributed in liver tissue. Their toxicity to lung and liver was evidently lower than injection. Nanoparticles' LD50 exceeded injection's by 13.5% and their stimulus was much lower than injection. The TBMS can be targeted to liver by liver targeted drug delivery system. At the same time, the problem about the toxicity hindering clinical application could be solved, which lays the foundation for the further studies on TBMS.

  11. New mechanisms for non-porative ultrasound stimulation of cargo delivery to cell cytosol with targeted perfluorocarbon nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Soman, N R; Marsh, J N; Lanza, G M; Wickline, S A [Washington University School of Medicine, Consortium for Translational Research in Advanced Imaging and Nanomedicine, CTRAIN, Campus Box 8215, St Louis, MO 63110 (United States)], E-mail: saw@wuphys.wustl.edu

    2008-05-07

    The cell membrane constitutes a major barrier for non-endocytotic intracellular delivery of therapeutic molecules from drug delivery vehicles. Existing approaches to breaching the cell membrane include cavitational ultrasound (with microbubbles), electroporation and cell-penetrating peptides. We report the use of diagnostic ultrasound for intracellular delivery of therapeutic bulky cargo with the use of molecularly targeted liquid perfluorocarbon (PFC) nanoparticles. To demonstrate the concept, we used a lipid with a surrogate polar head group, nanogold-DPPE, incorporated into the nanoparticle lipid monolayer. Melanoma cells were incubated with nanogold particles and this was followed by insonication with continuous wave ultrasound (2.25 MHz, 5 min, 0.6 MPa). Cells not exposed to ultrasound showed gold particles partitioned only in the outer bilayer of the cell membrane with no evidence of the intracellular transit of nanogold. However, the cells exposed to ultrasound exhibited numerous nanogold-DPPE components inside the cell that appeared polarized inside intracellular vesicles demonstrating cellular uptake and trafficking. Further, ultrasound-exposed cells manifested no incorporation of calcein or the release of lactate dehydrogenase. These observations are consistent with a mechanism that suggests that ultrasound is capable of stimulating the intracellular delivery of therapeutic molecules via non-porative mechanisms. Therefore, non-cavitational adjunctive ultrasound offers a novel paradigm in intracellular cargo delivery from PFC nanoparticles.

  12. New mechanisms for non-porative ultrasound stimulation of cargo delivery to cell cytosol with targeted perfluorocarbon nanoparticles

    International Nuclear Information System (INIS)

    Soman, N R; Marsh, J N; Lanza, G M; Wickline, S A

    2008-01-01

    The cell membrane constitutes a major barrier for non-endocytotic intracellular delivery of therapeutic molecules from drug delivery vehicles. Existing approaches to breaching the cell membrane include cavitational ultrasound (with microbubbles), electroporation and cell-penetrating peptides. We report the use of diagnostic ultrasound for intracellular delivery of therapeutic bulky cargo with the use of molecularly targeted liquid perfluorocarbon (PFC) nanoparticles. To demonstrate the concept, we used a lipid with a surrogate polar head group, nanogold-DPPE, incorporated into the nanoparticle lipid monolayer. Melanoma cells were incubated with nanogold particles and this was followed by insonication with continuous wave ultrasound (2.25 MHz, 5 min, 0.6 MPa). Cells not exposed to ultrasound showed gold particles partitioned only in the outer bilayer of the cell membrane with no evidence of the intracellular transit of nanogold. However, the cells exposed to ultrasound exhibited numerous nanogold-DPPE components inside the cell that appeared polarized inside intracellular vesicles demonstrating cellular uptake and trafficking. Further, ultrasound-exposed cells manifested no incorporation of calcein or the release of lactate dehydrogenase. These observations are consistent with a mechanism that suggests that ultrasound is capable of stimulating the intracellular delivery of therapeutic molecules via non-porative mechanisms. Therefore, non-cavitational adjunctive ultrasound offers a novel paradigm in intracellular cargo delivery from PFC nanoparticles

  13. New mechanisms for non-porative ultrasound stimulation of cargo delivery to cell cytosol with targeted perfluorocarbon nanoparticles

    Science.gov (United States)

    Soman, N. R.; Marsh, J. N.; Lanza, G. M.; Wickline, S. A.

    2008-05-01

    The cell membrane constitutes a major barrier for non-endocytotic intracellular delivery of therapeutic molecules from drug delivery vehicles. Existing approaches to breaching the cell membrane include cavitational ultrasound (with microbubbles), electroporation and cell-penetrating peptides. We report the use of diagnostic ultrasound for intracellular delivery of therapeutic bulky cargo with the use of molecularly targeted liquid perfluorocarbon (PFC) nanoparticles. To demonstrate the concept, we used a lipid with a surrogate polar head group, nanogold-DPPE, incorporated into the nanoparticle lipid monolayer. Melanoma cells were incubated with nanogold particles and this was followed by insonication with continuous wave ultrasound (2.25 MHz, 5 min, 0.6 MPa). Cells not exposed to ultrasound showed gold particles partitioned only in the outer bilayer of the cell membrane with no evidence of the intracellular transit of nanogold. However, the cells exposed to ultrasound exhibited numerous nanogold-DPPE components inside the cell that appeared polarized inside intracellular vesicles demonstrating cellular uptake and trafficking. Further, ultrasound-exposed cells manifested no incorporation of calcein or the release of lactate dehydrogenase. These observations are consistent with a mechanism that suggests that ultrasound is capable of stimulating the intracellular delivery of therapeutic molecules via non-porative mechanisms. Therefore, non-cavitational adjunctive ultrasound offers a novel paradigm in intracellular cargo delivery from PFC nanoparticles.

  14. BDNF gene delivery mediated by neuron-targeted nanoparticles is neuroprotective in peripheral nerve injury.

    Science.gov (United States)

    Lopes, Cátia D F; Gonçalves, Nádia P; Gomes, Carla P; Saraiva, Maria J; Pêgo, Ana P

    2017-03-01

    Neuron-targeted gene delivery is a promising strategy to treat peripheral neuropathies. Here we propose the use of polymeric nanoparticles based on thiolated trimethyl chitosan (TMCSH) to mediate targeted gene delivery to peripheral neurons upon a peripheral and minimally invasive intramuscular administration. Nanoparticles were grafted with the non-toxic carboxylic fragment of the tetanus neurotoxin (HC) to allow neuron targeting and were explored to deliver a plasmid DNA encoding for the brain-derived neurotrophic factor (BDNF) in a peripheral nerve injury model. The TMCSH-HC/BDNF nanoparticle treatment promoted the release and significant expression of BDNF in neural tissues, which resulted in an enhanced functional recovery after injury as compared to control treatments (vehicle and non-targeted nanoparticles), associated with an improvement in key pro-regenerative events, namely, the increased expression of neurofilament and growth-associated protein GAP-43 in the injured nerves. Moreover, the targeted nanoparticle treatment was correlated with a significantly higher density of myelinated axons in the distal stump of injured nerves, as well as with preservation of unmyelinated axon density as compared with controls and a protective role in injury-denervated muscles, preventing them from denervation. These results highlight the potential of TMCSH-HC nanoparticles as non-viral gene carriers to deliver therapeutic genes into the peripheral neurons and thus, pave the way for their use as an effective therapeutic intervention for peripheral neuropathies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. NIR fluorescent chitosan-based nanoparticles for tracking and delivery of cancer therapeutic molecule in living systems

    Science.gov (United States)

    Suarato, Giulia; Chin, Amanda; Meng, Yizhi

    2013-03-01

    Tumor metastasis is associated with the epithelial-to-mesenchymal transition (EMT), in which cells lose their polarized phenotype to acquire the asymmetry and motility of mesenchymal cells. Among the many molecular determinants for EMT is bone morphogenetic protein-7 (BMP-7), a critical regulator of skeletal tissue formation and kidney development. Current treatments for metastatic cancer primarily involve surgery and chemotherapy, both with considerable side effects. Therefore the goal of our research is to evaluate the ability of BMP-7 to reverse EMT using a delivery system based on glycol chitosan nanoparticles (GCNP), naturally biodegradable. The GCNP are labeled with Cy5.5, a near infrared (NIR) excitable dye that enables non-invasive imaging in living systems. The chitosan shell provides affinity for the cell surface and protection from intracellular enzymes during transport. Preliminary data show that Cy5.5-GCNP vehicles were successfully delivered to murine preosteoblast (MC3T3-E1), rat osteosarcoma (ROS) 17/2.8 and human embryonic kidney (HEK293) cells. Release kinetics using a model protein (BSA) and BMP-7, and the stability of the protein nano-cargo are currently being evaluated. Cell morphology will be examined with immunofluorescence microscopy.

  16. Facts and evidences on the lyophilization of polymeric nanoparticles for drug delivery.

    Science.gov (United States)

    Fonte, Pedro; Reis, Salette; Sarmento, Bruno

    2016-03-10

    Lyophilization has been used to improve the long-term stability of polymeric nanoparticles for drug delivery applications, avoiding their instability in suspension. However, this dehydration process may induce stresses to nanoparticles, mitigated by the use of some excipients such as cryo- and lyoprotectants. Still, the lyophilization of polymeric nanoparticles is frequently based in empirical principles, without considering the physical-chemical properties of formulations and the engineering principles of lyophilization. Therefore, the optimization of formulations and the lyophilization cycle is crucial to obtain a good lyophilizate, and guarantee the preservation of nanoparticle stability. The proper characterization of the lyophilizate and nanoparticles has a great importance in achieving these purposes. This review updates the fundaments involved in the optimization procedures for lyophilization of polymeric nanoparticles, with the aim of obtaining the maximum stability of formulations. Different characterization methods to obtain and guarantee a good lyophilized product are also discussed. A special focus is given to encapsulated therapeutic proteins. Overall, this review is a contribution for the understanding of the parameters involved in the lyophilization of polymeric nanoparticles. This may definitely help future works to obtain lyophilized nanoparticles with good quality and with improved therapeutic benefits. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Promotion of the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles combined with polypropylene electret.

    Science.gov (United States)

    Tu, Ye; Wang, Xinxia; Lu, Ying; Zhang, He; Yu, Yuan; Chen, Yan; Liu, Junjie; Sun, Zhiguo; Cui, Lili; Gao, Jing; Zhong, Yanqiang

    We recently reported that electret, which was prepared by a corona charging system with polypropylene film, could enhance the transdermal delivery of several drugs of low molecular weight. The aim of this study was to investigate whether electret could enhance the transdermal delivery of protein drugs by N -trimethyl chitosan nanoparticles (TMC NPs) prepared by an ionic gelation method. A series of experiments were performed, including in vitro skin permeation assays and anti-inflammatory effects, to evaluate the transdermal delivery of protein drugs by TMC NPs in the presence of electret. The results showed that in the presence of electret, the transdermal delivery of protein drugs in TMC NPs was significantly enhanced, as demonstrated by in vitro permeation studies and confocal laser scanning microscopy. Notably, superoxide dismutase-loaded TMC NPs combined with electret exhibited the best inhibitory effect on the edema of the mouse ear. TMC NPs combined with electret represent a novel platform for the transdermal delivery of protein drugs.

  18. Development of nanoantibiotic delivery system using cockle shell-derived aragonite nanoparticles for treatment of osteomyelitis

    Directory of Open Access Journals (Sweden)

    Saidykhan L

    2016-02-01

    Full Text Available Lamin Saidykhan,1 Md Zuki Bin Abu Bakar,2 Yaya Rukayadi,1,3 Aminu Umar Kura,4 Saiful Yazan Latifah5 1Microbiology Unit, Laboratory of Natural Products, Institute of Bioscience, 2Laboratory of Anatomy and Histology, Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, 3Department of Food Science, Faculty of Food Science and Technology, 4Vaccine and Immunotherapeutics Laboratory Unit, Institute of Bioscience, 5Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia Abstract: A local antibiotic delivery system (LADS with biodegradable drug vehicles is recognized as the most effective therapeutic approach for the treatment of osteomyelitis. However, the design of a biodegradable LADS with high therapeutic efficacy is too costly and demanding. In this research, a low-cost, facile method was used to design vancomycin-loaded aragonite nanoparticles (VANPs with the aim of understanding its potency in developing a nanoantibiotic bone implant for the treatment of osteomyelitis. The aragonite nanoparticles (ANPs were synthesized from cockle shells by a hydrothermal approach using a zwitterionic surfactant. VANPs were prepared using antibiotic ratios of several nanoparticles, and the formulation (1:4 with the highest drug-loading efficiency (54.05% was used for physicochemical, in vitro drug release, and biological evaluation. Physiochemical characterization of VANP was performed by using transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray powder diffraction, and Zetasizer. No significant differences were observed between VANP and ANP in terms of size and morphology as both samples were cubic shaped with sizes of approximately 35 nm. The Fourier transform infrared spectroscopy of VANP indicated a weak noncovalent interaction between ANP and vancomycin, while the zeta potential values were slightly increased from -19

  19. Arginine-Glycine-Aspartic Acid-Modified Lipid-Polymer Hybrid Nanoparticles for Docetaxel Delivery in Glioblastoma Multiforme.

    Science.gov (United States)

    Shi, Kairong; Zhou, Jin; Zhang, Qianyu; Gao, Huile; Liu, Yayuan; Zong, Taili; He, Qin

    2015-03-01

    Hybrid nanoparticles consisting of lipids and the biodegradable polymer, poly (D,L-lactide-co-glycolide) (PLGA), were developed for the targeted delivery of the anticancer drug, docetaxel. Transmission electron microscopic observations confirmed the presence of a lipid coating over the polymeric core. Using coumarin-6 as a fluorescent probe, the uptake efficacy of RGD conjugated lipid coated nanoparticles (RGD-L-P) by C6 cells was increased significantly, compared with that of lipid-polymer hybrid nanoparticles (L-P; 2.5-fold higher) or PLGA-nanoparticles (PLGA-P; 1.76-fold higher). The superior tumor spheroid penetration of RGD-L-P indicated that RGD-L-P could target effectively and specifically to C6 cells overexpressing integrin α(v)β3. The anti-proliferative activity of docetaxel-loaded RGD-L-P against C6 cells was increased 2.69- and 4.13-fold compared with L-P and PLGA-P, respectively. Regarding biodistribution, the strongest brain-localized fluorescence signals were detected in glioblastoma multiforme (GBM)-bearing rats treated with 1,10-Dioctadecyl-3,3,30,30-tetramethylindotricarb-ocyanine iodide (DiR)-loaded RGD-L-P, compared to rats treated with DiR-loaded L-P or PLGA-P. The median survival time of GBM-bearing rats treated with docetaxel-loaded RGD-L-P was 57 days, a fold increase of 1.43, 1.78, 3.35, and 3.56 compared with animals given L-P (P PLGA-P (P < 0.05), Taxotere (P < 0.01) and saline (P < 0.01), respectively. Collectively, these results support RGD-L-P as a promising drug delivery system for the specific targeting and the treatment of GBM.

  20. Multifunctional pH-Responsive Folate Receptor Mediated Polymer Nanoparticles for Drug Delivery.

    Science.gov (United States)

    Cai, Xiaoqing; Yang, Xiaoye; Wang, Fang; Zhang, Chen; Sun, Deqing; Zhai, Guangxi

    2016-07-01

    Multifunctional pH-responsive folate receptor mediated targeted polymer nanoparticles (TPNps) were developed for docetaxel (DTX) delivery based on poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)poly (β-amino ester) (P123-PAE) and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)-folate (P123-FA) copolymers. The DTX was loaded into the TPNps with a decent drug loading content of 15.02 ± 0.14 wt%. In vitro drug release results showed that the DTX was released from the TPNps at a pH-dependent manner. Tetrazolium dye (MTT) assay revealed that the bland polymer nanoparticles displayed almost nontoxicity at 200 μg/mL concentration. However, the DTX-loaded TPNps showed high anti-tumor activity at low IC50 (0.72 μg/mL) for MCF-7 cells following 48 h incubation. Cellular uptake experiments revealed that the TPNps had higher degree of cellular uptake than nontargeted polymer nanoparticles, indicating that the nanoparticles were internalized into the cells via FA receptor-mediated endocytosis. Moreover, the cellular uptake pathways for the FA grafted polymer were involved in energy-dependent, clathrin-mediated and caveolae-mediated endocytosis. The cell killing effect and cellular uptake of the DTX-TPNps by the MCF-7 cells were all enhanced by about two folds at pH 5.5 when compared with pH 7.4. The TPNps also significantly prolonged the in vivo retention time for the DTX. These results suggest that the biocompatible pH responsive folate-modified polymer nanoparticles present a promising safe nanosystem for intracellular targeted delivery of DTX.

  1. Micro- and Nano-Carrier Mediated Intra-Articular Drug Delivery Systems for the Treatment of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Zhiyue Zhang

    2012-01-01

    Full Text Available The objective of this paper is to provide readers with current developments of intra-articular drug delivery systems. In recent years, although the search for a clinically successful ideal carrier is ongoing, sustained-release systems, such as polymeric micro- and nanoparticles, liposomes, and hydrogels, are being extensively studied for intra-articular drug delivery purposes. The advantages associated with long-acting preparations include a longer effect of the drug in the action site and a reduced risk of infection due to numerous injections consequently. This paper discusses the recent developments in the field of intra-articular sustained-release delivery systems for the treatment of osteoarthritis.

  2. Micro- and Nano-Carrier Mediated Intra-Articular Drug Delivery Systems for the Treatment of Osteoarthritis

    International Nuclear Information System (INIS)

    Zhang, Z.; Huang, G.

    2012-01-01

    The objective of this paper is to provide readers with current developments of intra-articular drug delivery systems. In recent years, although the search for a clinically successful ideal carrier is ongoing, sustained-release systems, such as polymeric micro- and nanoparticles, liposomes, and hydrogels, are being extensively studied for intra-articular drug delivery purposes. The advantages associated with long-acting preparations include a longer effect of the drug in the action site and a reduced risk of infection due to numerous injections consequently. This paper discusses the recent developments in the field of intra-articular sustained-release delivery systems for the treatment of osteoarthritis

  3. Efficient intracellular delivery and improved biocompatibility of colloidal silver nanoparticles towards intracellular SERS immuno-sensing.

    Science.gov (United States)

    Bhardwaj, Vinay; Srinivasan, Supriya; McGoron, Anthony J

    2015-06-21

    High throughput intracellular delivery strategies, electroporation, passive and TATHA2 facilitated diffusion of colloidal silver nanoparticles (AgNPs) are investigated for cellular toxicity and uptake using state-of-art analytical techniques. The TATHA2 facilitated approach efficiently delivered high payload with no toxicity, pre-requisites for intracellular applications of plasmonic metal nanoparticles (PMNPs) in sensing and therapeutics.

  4. Nanoparticle-enabled delivery of surfactants in porous media.

    Science.gov (United States)

    Nourafkan, Ehsan; Hu, Zhongliang; Wen, Dongsheng

    2018-06-01

    The adsorption of surfactants on the reservoir rocks surface is a serious issue in many energy and environment related areas. Learning from the concept of drug delivery in the nano-medicine field, this work proposes and validates the concept of using nanoparticles to deliver a mixture of surfactants into a porous medium. TiO 2 nanoparticles (NPs) are used as carriers for a blend of surfactants mixtures including anionic alkyl aryl sulfonic acid (AAS) and nonionic alcohol ethoxylated (EA) at the optimum salinity and composition conditions. The transport of NPs through a core sample of crushed sandstone grains and the adsorption of surfactants are evaluated. By using TiO 2 NPs, the adsorption of surfactant molecules can be significantly reduced, i.e. half of the initial adsorption value. The level of surfactant adsorption reduction is related to the NPs transport capability through the porous medium. An application study shows that comparing to surfactant flooding alone, the total oil recovery can be increased by 7.81% of original oil in place (OOIP) by using nanoparticle bonded surfactants. Such work shows the promise of NP as an effective surfactant carrier for sandstone reservoirs, which could have many potential applications in enhanced oil recovery (EOR) and environmental remediation. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Advances in RNAi therapeutic delivery to leukocytes using lipid nanoparticles.

    Science.gov (United States)

    Ramishetti, Srinivas; Landesman-Milo, Dalit; Peer, Dan

    2016-11-01

    Small interfering RNAs (siRNAs) therapeutics has advanced into clinical trials for liver diseases and solid tumors, but remain a challenge for manipulating leukocytes fate due to lack of specificity and safety issues. Leukocytes ingest pathogens and defend the body through a complex network. They are also involved in the pathogeneses of inflammation, viral infection, autoimmunity and cancers. Modulating gene expression in leukocytes using siRNAs holds great promise to treat leukocyte-mediated diseases. Leukocytes are notoriously hard to transduce with siRNAs and are spread throughout the body often located deep in tissues, therefore developing an efficient systemic delivery strategy is still a challenge. Here, we discuss recent advances in siRNA delivery to leukocyte subsets such as macrophages, monocytes, dendritic cells and lymphocytes. We focus mainly on lipid-based nanoparticles (LNPs) comprised of new generation of ionizable lipids and their ability to deliver siRNA to primary or malignant leukocytes in a targeted manner. Special emphasis is made on LNPs targeted to subsets of leukocytes and we detail a novel microfluidic mixing technology that could aid in changing the landscape of process development of LNPs from a lab tool to a potential novel therapeutic modality.

  6. Using DNA nanotechnology to produce a drug delivery system

    International Nuclear Information System (INIS)

    La, Thi Huyen; Nguyen, Thi Thu Thuy; Pham, Van Phuc; Nguyen, Thi Minh Huyen; Le, Quang Huan

    2013-01-01

    Drug delivery to cancer cells in chemotherapy is one of the most advanced research topics. The effectiveness of the current cancer treatment drugs is limited because they are not capable of distinguishing between cancer cells and normal cells so that they kill not only cancer cells but also normal ones. To overcome this disadvantage by profiting from the differences in physical and chemical properties between cancer and normal cells, nanoparticles (NPs) delivering a drug are designed in a specific manner such that they can distinguish the cancer cells from the normal ones and are targeted only to the cancer cells. Currently, there are various drug delivery systems with many advantages, but sharing some common disadvantages such as difficulty with controlling the size, low encapsulation capacity and low stability. With the development and success of DNA nanotechnology, DNA strands are used to create effective drug delivery NPs with precisely controlled size and structure, safety and high stability. This article presents our study on drug encapsulation in DNA nanostructure which loaded docetaxel and curcumin in a desire to create a new and effective drug delivery system with high biological compatibility. (paper)

  7. Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a potential Anticancer Drug Delivery System

    Science.gov (United States)

    Patel, Meghavi

    with a well-defined shell and the particle size was in agreement with the particle size analysis data obtained by DLS. DSC thermograms of the lyophilized SLNs indicate a reduction in the crystallinity order of GMS particles. The drug encapsulation efficiency was found to be approximately 30%. In vitro drug release studies from redispersed lyophilized SLNs showed that 17 % of the encapsulated drug was released within 2 h. The SLNs prepared in our lab demonstrated characteristics that can potentially be utilized in an anticancer drug delivery system. Future in vitro cell culture and in vivo animal model studies will delineate compatibility and utility of these formulations in biological systems.

  8. Chitosan-Poly (I:C-PADRE Based Nanoparticles as Delivery Vehicles for Synthetic Peptide Vaccines

    Directory of Open Access Journals (Sweden)

    Jorge F. Correia-Pinto

    2015-09-01

    Full Text Available The safety and precision of peptide antigens has prompted the search for adjuvants capable of increasing the immune response against these intrinsically poorly immunogenic antigens. The integration of both immunostimulants and peptide antigens within nanometric delivery systems for their co-delivery to immune cells is a promising vaccination strategy. With this in mind, the potential synergistic effect of the immunostimulant poly (I:C (pIC and a T-Helper peptide (PADRE, integrated into a chitosan (CS based nanostructure, was explored. The value of this nanostructured combination of materials was assessed for a peptide antigen (1338aa derived from the HPV-16 L2 protein. These nanoparticles, produced by ionic gelation technique, exhibited a nanometric size (<300 nm, a high positive surface charge (>40 mV and high pIC association efficiency (>96%. They also showed capacity for the association of both the 1338aa and PADRE peptides. The influence of the presence of pIC and PADRE in the nanocomposition, as well as that of the peptide presentation form (encapsulated versus surface adsorbed on the antibody induction was evaluated in a preliminary in vivo study. The data obtained highlights the possibility to engineer nanoparticles through the rational combination of a number of adjuvant molecules together with the antigen.

  9. Improvement of interaction between PVA and chitosan via magnetite nanoparticles for drug delivery application.

    Science.gov (United States)

    Shagholani, Hamidreza; Ghoreishi, Sayed Mehdi; Mousazadeh, Mohammad

    2015-01-01

    Magnetite nanoparticles were synthesized by coprecipitation under ultrasonication followed by coating with chitosan. Polyvinyl alcohol (PVA) is then combined with the chitosan that coated the magnetite nanoparticles. The combination occurs by hydrogen binding and ionic cross-linking of the amino and hydroxyl groups of chitosan and PVA respectively. The magnetite nanoparticles have an average size of 10.62 nm that was confirmed by TEM. The VSM measurements showed that nanoparticles were superparamagnetic. The coatings on the core nanoparticles were estimated by AAS and the attachments of coating to the nanoparticles were confirmed by FT-IR analysis. Physicochemical properties of nanoparticles were measured by DLS and zeta potential. Naked magnetite, chitosan and PVA coating have zeta potential of +36.4, +48.1 and -12.5 mV respectively. The unspecific adsorption and interaction between nanoparticles and bovine serum albumin (BSA) were investigated systematically by UV-vis spectroscopy method. The nanoparticles that were modified by PVA present low protein adsorption, which makes them a practical choice for preventing opsonization in clinical application and drug delivery. Copyright © 2015. Published by Elsevier B.V.

  10. Comparison of chitosan nanoparticles and chitosan hydrogels for vaccine delivery

    DEFF Research Database (Denmark)

    Gordon, Sarah; Saupe, Anne; McBurney, Warren

    2008-01-01

    In this work the potential of chitosan nanoparticles (CNP) and thermosensitive chitosan hydrogels as particulate and sustained release vaccine delivery systems was investigated. CNP and chitosan hydrogels were prepared, loaded with the model protein antigen ovalbumin (OVA) and characterised...... of the release of fluorescently-labelled OVA (FITC-OVA) from CNP and chitosan hydrogels in-vitro showed that approximately 50% of the total protein was released from CNP within a period of ten days; release of antigen from chitosan gel occurred in a more sustained manner, with ... released after 10 days. The slow release from gel formulations may be explained by the strong interactions of the protein with chitosan. While OVA-loaded CNP showed no significant immunogenicity, formulations of OVA in chitosan gel were able to stimulate both cell-mediated and humoral immunity in-vivo....

  11. A high-density lipoprotein-mediated drug delivery system.

    Science.gov (United States)

    Mo, Zhong-Cheng; Ren, Kun; Liu, Xing; Tang, Zhen-Li; Yi, Guang-Hui

    2016-11-15

    High-density lipoprotein (HDL) is a comparatively dense and small lipoprotein that can carry lipids as a multifunctional aggregate in plasma. Several studies have shown that increasing the levels or improving the functionality of HDL is a promising target for treating a wide variety of diseases. Among lipoproteins, HDL particles possess unique physicochemical properties, including naturally synthesized physiological components, amphipathic apolipoproteins, lipid-loading and hydrophobic agent-incorporating characteristics, specific protein-protein interactions, heterogeneity, nanoparticles, and smaller size. Recently, the feasibility and superiority of using HDL particles as drug delivery vehicles have been of great interest. In this review, we summarize the structure, constituents, biogenesis, remodeling, and reconstitution of HDL drug delivery systems, focusing on their delivery capability, characteristics, applications, manufacturing, and drug-loading and drug-targeting characteristics. Finally, the future prospects are presented regarding the clinical application and challenges of using HDL as a pharmacodelivery carrier. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Drug delivery system and breast cancer cells

    Science.gov (United States)

    Colone, Marisa; Kaliappan, Subramanian; Calcabrini, Annarica; Tortora, Mariarosaria; Cavalieri, Francesca; Stringaro, Annarita

    2016-06-01

    Recently, nanomedicine has received increasing attention for its ability to improve the efficacy of cancer therapeutics. Nanosized polymer therapeutic agents offer the advantage of prolonged circulation in the blood stream, targeting to specific sites, improved efficacy and reduced side effects. In this way, local, controlled delivery of the drug will be achieved with the advantage of a high concentration of drug release at the target site while keeping the systemic concentration of the drug low, thus reducing side effects due to bioaccumulation. Various drug delivery systems such as nanoparticles, liposomes, microparticles and implants have been demonstrated to significantly enhance the preventive/therapeutic efficacy of many drugs by increasing their bioavailability and targetability. As these carriers significantly increase the therapeutic effect of drugs, their administration would become less cost effective in the near future. The purpose of our research work is to develop a delivery system for breast cancer cells using a microvector of drugs. These results highlight the potential uses of these responsive platforms suited for biomedical and pharmaceutical applications. At the request of all authors of the paper an updated version was published on 12 July 2016. The manuscript was prepared and submitted without Dr. Francesca Cavalieri's contribution and her name was added without her consent. Her name has been removed in the updated and re-published article.

  13. Substrate-mediated delivery of gene complex nanoparticles via polydopamine coating for enhancing competitiveness of endothelial cells.

    Science.gov (United States)

    Li, Bo-Chao; Chang, Hao; Ren, Ke-Feng; Ji, Jian

    2016-11-01

    Substrate-mediated delivery of functional plasmid DNA (pDNA) has been proven to be a promising strategy to promote competitiveness of endothelial cells (ECs) over smooth muscle cells (SMCs), which is beneficial to inducing fast endothelialization of implanted vascular devices. Thus, it is of great importance to develop universal approaches with simplicity and easiness to immobilize DNA complex nanoparticles on substrates. In this study, the bioinspired polydopamine (PDA) coating was employed in immobilization of DNA complex nanoparticles, which were composed of protamine (PrS) and plasmid DNA encoding with hepatocyte growth factor (HGF-pDNA) gene. We demonstrated that the DNA complex nanoparticles can be successfully immobilized onto the PDA surface. Consequently, the HGF expression of both ECs and SMCs were significantly improved when they cultured on the DNA complex nanoparticles-immobilized substrates. Furthermore, EC proliferation was specifically promoted due to bioactivity of HGF, leading to an enhancement of EC competitiveness over SMCs. Our findings demonstrated the substrate-mediated functional gene nanoparticle delivery through PDA coating as a simple and efficient approach. It may hold great potential in the field of interventional cardiovascular implants. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Nanoengineered mesoporous silica nanoparticles for smart delivery of doxorubicin

    Science.gov (United States)

    Mishra, Akhilesh Kumar; Pandey, Himanshu; Agarwal, Vishnu; Ramteke, Pramod W.; Pandey, Avinash C.

    2014-08-01

    The motive of the at hand exploration was to contrive a proficient innovative pH-responsive nanocarrier designed for an anti-neoplastic agent that not only owns competent loading capacity but also talented to liberate the drug at the specific site. pH sensitive hollow mesoporous silica nanoparticles ( MSN) have been synthesized by sequence of chemical reconstruction with an average particle size of 120 nm. MSN reveal noteworthy biocompatibility and efficient drug loading magnitude. Active molecules such as Doxorubicin (DOX) can be stocked and set free from the pore vacuities of MSN by tuning the pH of the medium. The loading extent of MSN was found up to 81.4 wt% at pH 7.8. At mild acidic pH, DOX is steadily released from the pores of MSN. Both, the nitrogen adsorption-desorption isotherms and X-ray diffraction patterns reflects that this system holds remarkable stable mesostructure. Additionally, the outcomes of cytotoxicity assessment further establish the potential of MSN as a relevant drug transporter which can be thought over an appealing choice to a polymeric delivery system.

  15. The Inclusion of Chitosan in Poly-ε-caprolactone Nanoparticles: Impact on the Delivery System Characteristics and on the Adsorbed Ovalbumin Secondary Structure.

    Science.gov (United States)

    Jesus, Sandra; Fragal, Elizangela H; Rubira, Adley F; Muniz, Edvani C; Valente, Artur J M; Borges, Olga

    2018-01-01

    This report extensively explores the benefits of including chitosan into poly-ε-caprolactone (PCL) nanoparticles (NPs) to obtain an improved protein/antigen delivery system. Blend NPs (PCL/chitosan NPs) showed improved protein adsorption efficacy (84%) in low shear stress and aqueous environment, suggesting that a synergistic effect between PCL hydrophobic nature and the positive charges of chitosan present at the particle surface was responsible for protein interaction. Additionally, thermal analysis suggested the blend NPs were more stable than the isolated polymers and cytotoxicity assays in a primary cell culture revealed chitosan inclusion in PCL NPs reduced the toxicity of the delivery system. A quantitative 6-month stability study showed that the inclusion of chitosan in PCL NPs did not induce a change in adsorbed ovalbumin (OVA) secondary structure characterized by the increase in the unordered conformation (random coil), as it was observed for OVA adsorbed to chitosan NPs. Additionally, the slight conformational changes occurred, are not expected to compromise ovalbumin secondary structure and activity, during a 6-month storage even at high temperatures (45°C). In simulated biological fluids, PCL/chitosan NPs showed an advantageous release profile for oral delivery. Overall, the combination of PCL and chitosan characteristics provide PCL/chitosan NPs valuable features particularly important to the development of vaccines for developing countries, where it is difficult to ensure cold chain transportation and non-parenteral formulations would be preferred.

  16. Mesoporous Silica and Organosilica Nanoparticles: Physical Chemistry, Biosafety, Delivery Strategies, and Biomedical Applications

    KAUST Repository

    Croissant, Jonas G.

    2017-11-30

    Predetermining the physico-chemical properties, biosafety, and stimuli-responsiveness of nanomaterials in biological environments is essential for safe and effective biomedical applications. At the forefront of biomedical research, mesoporous silica nanoparticles and mesoporous organosilica nanoparticles are increasingly investigated to predict their biological outcome by materials design. In this review, it is first chronicled that how the nanomaterial design of pure silica, partially hybridized organosilica, and fully hybridized organosilica (periodic mesoporous organosilicas) governs not only the physico-chemical properties but also the biosafety of the nanoparticles. The impact of the hybridization on the biocompatibility, protein corona, biodistribution, biodegradability, and clearance of the silica-based particles is described. Then, the influence of the surface engineering, the framework hybridization, as well as the morphology of the particles, on the ability to load and controllably deliver drugs under internal biological stimuli (e.g., pH, redox, enzymes) and external noninvasive stimuli (e.g., light, magnetic, ultrasound) are presented. To conclude, trends in the biomedical applications of silica and organosilica nanovectors are delineated, such as unconventional bioimaging techniques, large cargo delivery, combination therapy, gaseous molecule delivery, antimicrobial protection, and Alzheimer\\'s disease therapy.

  17. Biopolymer mediated nanoparticles synthesized from Adenia hondala for enhanced tamoxifen drug delivery in breast cancer cell line

    Science.gov (United States)

    Varadharajaperumal, Pradeepa; Subramanian, Balakumar; Santhanam, Amutha

    2017-09-01

    Silver nanoparticles (AgNPs) are an important class of nanomaterials, which have used as antimicrobial and disinfectant agents due to their detrimental effect on target cells. In the present study it was explored to deliver a novel tamoxifen drug system that can be used in breast cancer treatment, based on chitosan coated silver nanoparticles on MCF-7 human breast cancer cells. AgNPs synthesized from Adenia hondala tuber extract were used to make the chitosan coated AgNPs (Ch-AgNPs), in which the drug tamoxifen was loaded on chitosan coated silver nanoparticles (Tam-Ch-AgNPs) to construct drug loaded nanoparticles as drug delivery system. The morphology and characteristics of the Ch-AgNPs were investigated by UV, FTIR, zeta potential and FESEM. Furthermore, the toxicity of AgNPs, Ch-AgNPs, Tam-Ch-AgNPs was evaluated through cell viability, lactate dehydrogenase leakage, reactive oxygen species generation, caspase-3, DNA laddering, and TUNEL assay in human breast cancer cells (MCF-7) and HBL-100 continuous cell line as a control. Treatment of cancer cells with various concentrations of AgNPs, Ch-AgNPs, Tam-Ch-AgNPs for 24 h revealed that Tam-Ch-AgNPs could inhibit cell viability and induce significant membrane leakage in a dose-dependent manner. Cells exposed to Tam-Ch-AgNPs showed increased reactive oxygen species and hydroxyl radical production when compared to AgNPs, Ch-AgNPs. Furthermore, the apoptotic effects of AgNPs, Ch-AgNPs, Tam-Ch-AgNPs were confirmed by activation of caspase-3 and DNA nuclear fragmentation. The present findings suggest that Tam-Ch-AgNPs could contribute to the development of a suitable anticancer drug delivery.

  18. Multifunctional organic–inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery

    Directory of Open Access Journals (Sweden)

    Chi H

    2017-02-01

    Full Text Available Huibo Chi,1,2,* Yan Gu,1,* Tingting Xu,1 Feng Cao1 1Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 2State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research Co., Ltd., Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: To study the cellular uptake mechanism of multifunctional organic–inorganic hybrid nanoparticles and nanosheets, new chitosan–glutathione–valine–valine-layered double hydroxide (CG-VV-LDH nanosheets with active targeting to peptide transporter-1 (PepT-1 were prepared, characterized and further compared with CG-VV-LDH nanoparticles. Both organic–inorganic hybrid nanoparticles and nanosheets showed a sustained release in vitro and prolonged precorneal retention time in vivo, but CG-VV-LDH nanoparticles showed superior permeability in the isolated cornea of rabbits than CG-VV-LDH nanosheets. Furthermore, results of cellular uptake on human corneal epithelial primary cells (HCEpiC and retinal pigment epithelial (ARPE-19 cells indicated that both clathrin-mediated endocytosis and active transport of PepT-1 are involved in the internalization of CG-VV-LDH nanoparticles and CG-VV-LDH nanosheets. In summary, the CG-VV-LDH nanoparticle may be a promising carrier as a topical ocular drug delivery system for the treatment of ocular diseases of mid-posterior segments, while the CG-VV-LDH nanosheet may be suitable for the treatment of ocular surface diseases. Keywords: LDH nanoparticles, LDH nanosheets, ocular drug delivery, human corneal epithelial primary cell, retinal pigment cell, ARPE-19, active targeting

  19. Micelles As Delivery System for Cancer Treatment.

    Science.gov (United States)

    Keskin, Dilek; Tezcaner, Aysen

    2017-01-01

    Micelles are nanoparticles formed by the self-assembly of amphiphilic block copolymers in certain solvents above concentrations called critical micelle concentration (CMC). Micelles are used in different fields like food, cosmetics, medicine, etc. These nanosized delivery systems are under spotlight in the recent years with new achievements in terms of their in vivo stability, ability to protect entrapped drug, release kinetics, ease of cellular penetration and thereby increased therapeutic efficacy. Drug loaded micelles can be prepared by dialysis, oil-in-water method, solid dispersion, freezing, spray drying, etc. The aim of this review is to give an overview of the research on micelles (in vitro, in vivo and clinical) as delivery system for cancer treatment. Passive targeting is one route for accumulation of nanosized micellar drug formulations. Many research groups from both academia and industry focus on developing new strategies for improving the therapeutic efficacy of micellar systems (active targeting to the tumor site, designing multidrug delivery systems for overcoming multidrug resistance or micelles formed by prodrug conjugates, etc). There is only one micellar drug formulation in South Korea that has reached clinical practice. However, there are many untargeted anticancer drug loaded micellar formulations in clinical trials, which have potential for use in clinics. Many more products are expected to be on the market in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Incorporation of liquid lipid in lipid nanoparticles for ocular drug delivery enhancement

    International Nuclear Information System (INIS)

    Shen Jie; Sun Minjie; Ping Qineng; Ying Zhi; Liu Wen

    2010-01-01

    The present work investigates the effect of liquid lipid incorporation on the physicochemical properties and ocular drug delivery enhancement of nanostructured lipid carriers (NLCs) and attempts to elucidate in vitro and in vivo the potential of NLCs for ocular drug delivery. The CyA-loaded or fluorescein-marked nanocarriers composed of Precifac ATO 5 and Miglyol 840 (as liquid lipid) were prepared by melting-emulsion technology, and the physicochemical properties of nanocarriers were determined. The uptake of nanocarriers by human corneal epithelia cell lines (SDHCEC) and rabbit cornea was examined. Ex vivo fluorescence imaging was used to investigate the ocular distribution of nanocarriers. The in vitro cytotoxicity and in vivo acute tolerance were evaluated. The higher drug loading capacity and improved in vitro sustained drug release behavior of lipid nanoparticles was found with the incorporation of liquid lipid in lipid nanoparticles. The uptake of nanocarriers by the SDHCEC was increased with the increase in liquid lipid loading. The ex vivo fluorescence imaging of the ocular tissues indicated that the liquid lipid incorporation could improve the ocular retention and penetration of ocular therapeutics. No alternation was macroscopically observed in vivo after ocular surface exposure to nanocarriers. These results indicated that NLC was a biocompatible and potential nanocarrier for ocular drug delivery enhancement.

  1. Incorporation of liquid lipid in lipid nanoparticles for ocular drug delivery enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Shen Jie; Sun Minjie; Ping Qineng; Ying Zhi; Liu Wen, E-mail: Pingqn2004@yahoo.com.cn [School of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing (China)

    2010-01-15

    The present work investigates the effect of liquid lipid incorporation on the physicochemical properties and ocular drug delivery enhancement of nanostructured lipid carriers (NLCs) and attempts to elucidate in vitro and in vivo the potential of NLCs for ocular drug delivery. The CyA-loaded or fluorescein-marked nanocarriers composed of Precifac ATO 5 and Miglyol 840 (as liquid lipid) were prepared by melting-emulsion technology, and the physicochemical properties of nanocarriers were determined. The uptake of nanocarriers by human corneal epithelia cell lines (SDHCEC) and rabbit cornea was examined. Ex vivo fluorescence imaging was used to investigate the ocular distribution of nanocarriers. The in vitro cytotoxicity and in vivo acute tolerance were evaluated. The higher drug loading capacity and improved in vitro sustained drug release behavior of lipid nanoparticles was found with the incorporation of liquid lipid in lipid nanoparticles. The uptake of nanocarriers by the SDHCEC was increased with the increase in liquid lipid loading. The ex vivo fluorescence imaging of the ocular tissues indicated that the liquid lipid incorporation could improve the ocular retention and penetration of ocular therapeutics. No alternation was macroscopically observed in vivo after ocular surface exposure to nanocarriers. These results indicated that NLC was a biocompatible and potential nanocarrier for ocular drug delivery enhancement.

  2. Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye - Part II - Ocular drug-loaded lipid nanoparticles.

    Science.gov (United States)

    Sánchez-López, E; Espina, M; Doktorovova, S; Souto, E B; García, M L

    2017-01-01

    In the recent decades, various controlled delivery systems have been introduced with the aim to improve solubility, stability and bioavailability of poorly absorbed drugs. Among all, lipid nanoparticles gather interesting properties as drug or gene delivery carriers. These systems, composed either of solid lipids (SLN) or of solid and liquid lipids (NLC) stabilized with surfactants, combine the advantages of other colloidal particles such as polymeric nanoparticles, fat emulsions and liposomes avoiding their main disadvantages. Lipid nanoparticles represent an interesting approach for eye drug delivery as they can improve the corneal absorption of drugs enhancing their bioavailability. The Generally Recognized as Safe status of formulation excipients, the scaling-up facilities and the possibility of sterilization, make them suitable for industrial production. In this review, the latest findings, potential applications, and challenges related to the use of lipid nanoparticles for ocular drug delivery are comprehensively discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Intraspinal Delivery of Polyethylene Glycol-coated Gold Nanoparticles Promotes Functional Recovery After Spinal Cord Injury.

    Science.gov (United States)

    Papastefanaki, Florentia; Jakovcevski, Igor; Poulia, Nafsika; Djogo, Nevena; Schulz, Florian; Martinovic, Tamara; Ciric, Darko; Loers, Gabrielle; Vossmeyer, Tobias; Weller, Horst; Schachner, Melitta; Matsas, Rebecca

    2015-06-01

    Failure of the mammalian central nervous system (CNS) to regenerate effectively after injury leads to mostly irreversible functional impairment. Gold nanoparticles (AuNPs) are promising candidates for drug delivery in combination with tissue-compatible reagents, such as polyethylene glycol (PEG). PEG administration in CNS injury models has received interest for potential therapy, but toxicity and low bioavailability prevents clinical application. Here we show that intraspinal delivery of PEG-functionalized 40-nm-AuNPs at early stages after mouse spinal cord injury is beneficial for recovery. Positive outcome of hind limb motor function was accompanied by attenuated inflammatory response, enhanced motor neuron survival, and increased myelination of spared or regrown/sprouted axons. No adverse effects, such as body weight loss, ill health, or increased mortality were observed. We propose that PEG-AuNPs represent a favorable drug-delivery platform with therapeutic potential that could be further enhanced if PEG-AuNPs are used as carriers of regeneration-promoting molecules.

  4. Nanosized Minicells Generated by Lactic Acid Bacteria for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Huu Ngoc Nguyen

    2017-01-01

    Full Text Available Nanotechnology has the ability to target specific areas of the body, controlling the drug release and significantly increasing the bioavailability of active compounds. Organic and inorganic nanoparticles have been developed for drug delivery systems. Many delivery systems are through clinical stages for development and market. Minicell, a nanosized cell generated by bacteria, is a potential particle for drug delivery because of its size, safety, and biodegradability. Minicells produced by bacteria could drive therapeutic agents against cancer, microbial infection, and other diseases by targeting. In addition, minicells generated by lactic acid bacteria being probiotics are more interesting than others because of their benefits like safety, immunological improvement, and biodegradation. This review aims to highlight the stages of development of nanoparticle for drug delivery and discuss their advantages and limitations to clarify minicells as a new opportunity for the development of potential nanoparticle for drug delivery.

  5. Polyelectrolyte Multilayer Film Coated Silver Nanorods: An Effective Carrier System for Externally Activated Drug Delivery

    Science.gov (United States)

    Paramasivam, Gokul; Sharma, Varsha; Sundaramurthy, Anandhakumar

    2017-08-01

    Nanoparticle anisotropy offers unique functions and features in comparison with spherical nanoparticles (NPs) and makes anisotropic nanoparticles (ANPs) promising candidates in applications like drug delivery, imaging, biosensing and theranostics. Presence of surface active groups (e.g. amine, and carboxylate groups) on their surface provides binding sites for ligands or other biomolecules, and hence, this could be targeted for specific part or cells in our body. In the quest of such surface modification, functionalization of ANPs along Layer-by-Layer (LbL) coating of oppositely charged polyelectrolytes (PE) reduces cellular toxicity and promotes easy encapsulation of drugs. In this work, we report the silver nanorods (AgNRs) synthesis by adsorbate directed synthetic approach using cetyltrimethyl ammonium bromide (CTAB). The formed ANPs is investigated by scanning electron microscopy (SEM) and UV-Visible (UV-Vis) spectroscopy revealing the shaping of AgNRs of 3-16 nm aspect ratio with some presence of triangles. These NRs were further coated with bio polymers of chitosan (CH) and dextran sulphate (DS) through LbL approach and used for encapsulation of water soluble anti-bacterial drugs like ciprofloxacin hydrochloride (CFH). The encapsulation of drugs and profiles of drug release were investigated and compared to that of spherical silver nanoparticles (AgNPs). The added advantages of the proposed drug delivery system (DDS) can be externally activated to release the loaded drug and used as contrast agents for biological imaging under exposure to NIR light. Such system shows unique and attractive characteristics required for drug delivery and bioimaging thus offering the scope for further development as theranostic material.

  6. Chitosan nanoparticles for targeting and sustaining minoxidil sulphate delivery to hair follicles.

    Science.gov (United States)

    Matos, Breno Noronha; Reis, Thaiene Avila; Gratieri, Taís; Gelfuso, Guilherme Martins

    2015-04-01

    This work developed minoxidil sulphate-loaded chitosan nanoparticles (MXS-NP) for targeted delivery to hair follicles, which could sustain drug release and improve the topical treatment of alopecia. Chitosan nanoparticles were obtained using low-molecular weight chitosan and tripolyphosphate as crosslink agent. MXS-NP presented a monomodal distribution with hydrodynamic diameter of 235.5 ± 99.9 nm (PDI of 0.31 ± 0.01) and positive zeta potential (+38.6 ± 6.0 mV). SEM analysis confirmed nanoparticles average size and spherical shape. A drug loading efficiency of 73.0 ± 0.3% was obtained with polymer:drug ratio of 1:1 (w/w). Drug release through cellulose acetate membranes from MXS-NP was sustained in about 5 times in comparison to the diffusion rate of MXS from the solution (188.9 ± 6.0 μg/cm(2)/h and 35.4 ± 1.8 μg/cm(2)/h). Drug permeation studies through the skin in vitro, followed by selective recovery of MXS from the hair follicles, showed that MXS-NP application resulted in a two-fold MXS increase into hair follicles after 6h in comparison to the control solution (5.9 ± 0.6 μg/cm(2) and 2.9 ± 0.8 μg/cm(2)). MXS-loading in nanoparticles appears as a promising and easy strategy to target and sustain drug delivery to hair follicles, which may improve the topical treatment of alopecia. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Synthesis and characterization of amino acid-functionalized calcium phosphate nanoparticles for siRNA delivery.

    Science.gov (United States)

    Bakan, Feray; Kara, Goknur; Cokol Cakmak, Melike; Cokol, Murat; Denkbas, Emir Baki

    2017-10-01

    Small interfering RNAs (siRNA) are short nucleic acid fragments of about 20-27 nucleotides, which can inhibit the expression of specific genes. siRNA based RNAi technology has emerged as a promising method for the treatment of a variety of diseases. However, a major limitation in the therapeutic use of siRNA is its rapid degradation in plasma and cellular cytoplasm, resulting in short half-life. In addition, as siRNA molecules cannot penetrate into the cell efficiently, it is required to use a carrier system for its delivery. In this work, chemically and morphologically different calcium phosphate (CaP) nanoparticles, including spherical-like hydroxyapatite (HA-s), needle-like hydroxyapatite (HA-n) and calcium deficient hydroxyapatite (CDHA) nanoparticles were synthesized by the sol-gel technique and the effects of particle characteristics on the binding capacity of siRNA were investigated. In order to enhance the gene loading efficiency, the nanoparticles were functionalized with arginine and the morphological and their structural characteristics were analyzed. The addition of arginine did not significantly change the particle sizes; however, it provided a significantly increased binding of siRNA for all types of CaP nanoparticles, as revealed by spectrophotometric measurements analysis. Arginine functionalized HA-n nanoparticles showed the best binding behavior with siRNA among the other nanoparticles due to its high, positive zeta potential (+18.8mV) and high surface area of Ca ++ rich "c" plane. MTT cytotoxicity assays demonstrated that all the nanoparticles tested herein were biocompatible. Our results suggest that high siRNA entrapment in each of the three modified non-toxic CaP nanoparticles make them promising candidates as a non-viral vector for delivering therapeutic siRNA molecules to treat cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel

    Directory of Open Access Journals (Sweden)

    Khosravian P

    2016-12-01

    Full Text Available Pegah Khosravian,1 Mehdi Shafiee Ardestani,2 Mehdi Khoobi,3 Seyed Naser Ostad,4 Farid Abedin Dorkoosh,1 Hamid Akbari Javar,1,* Massoud Amanlou5,6,* 1Department of Pharmaceutics, 2Department of Radiopharmacy, 3Department of Pharmaceutical Biomaterials, 4Department of Pharmacology and Toxicology, 5Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, 6Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran *These authors contributed equally to this work Abstract: Mesoporous silica nanoparticles (MSNs are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this study, a series of docetaxel-loaded folic acid- or methionine-functionalized mesoporous silica nanoparticles (DTX/MSN-FA or DTX/MSN-Met with large pores and amine groups at inner pore surface properties were prepared. The results showed that the MSNs were successfully synthesized, having good pay load and pH-sensitive drug release kinetics. The cellular investigation on MCF-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of targeted nanoparticles. In vivo fluorescent imaging on healthy BALB/c mice proved that bare MSN-NH2 are mostly accumulated in the liver but MSN-FA or MSN-Met are more concentrated in the kidney. Importantly, ex vivo fluorescent images of tumor-induced BALB/c mice organs revealed the ability of MSN-FA to reach the tumor tissues. In conclusion, DTX/MSNs exhibited a good anticancer activity and enhanced the possibility of targeted drug delivery for breast cancer. Keywords: targeted delivery, mesoporous silica nanoparticle, folic acid, methionine, docetaxel

  9. A pH-Sensitive Injectable Nanoparticle Composite Hydrogel for Anticancer Drug Delivery

    Directory of Open Access Journals (Sweden)

    Yuanfeng Ye

    2016-01-01

    Full Text Available According to previous reports, low pH-triggered nanoparticles were considered to be excellent carriers for anticancer drug delivery, for the reason that they could trigger encapsulated drug release at mild acid environment of tumor. Herein, an acid-sensitive β-cyclodextrin derivative, namely, acetalated-β-cyclodextrin (Ac-β-CD, was synthesized by acetonation and fabricated to nanoparticles through single oil-in-water (o/w emulsion technique. At the same time, camptothecin (CPT, a hydrophobic anticancer drug, was encapsulated into Ac-β-CD nanoparticles in the process of nanoparticle fabrication. Formed nanoparticles exhibited nearly spherical structure with diameter of 209±40 nm. The drug release behavior of nanoparticles displayed pH dependent changes due to hydrolysis of Ac-β-CD. In order to overcome the disadvantages of nanoparticle and broaden its application, injectable hydrogels with Ac-β-CD nanoparticles were designed and prepared by simple mixture of nanoparticles solution and graphene oxide (GO solution in this work. The injectable property was confirmed by short gelation time and good mobility of two precursors. Hydrogels were characterized by dynamic mechanical test and SEM, which also reflected some structural features. Moreover, all hydrogels underwent a reversible sol-gel transition in alkaline environment. Finally, the results of in vitro drug release profile indicated that hydrogel could control drug release or bind drug inside depending on the pH value of released medium.

  10. Study of Mesoporous Silica Nanoparticles' (MSNs) intracellular trafficking and their application as drug delivery vehicles

    Science.gov (United States)

    Yanes, Rolando Eduardo

    Mesoporous silica nanoparticles (MSNs) are attractive drug delivery vehicle candidates due to their biocompatibility, stability, high surface area and efficient cellular uptake. In this dissertation, I discuss three aspects of MSNs' cellular behavior. First, MSNs are targeted to primary and metastatic cancer cell lines, then their exocytosis from cancer cells is studied, and finally they are used to recover intracellular proteins. Targeting of MSNs to primary cancer cells is achieved by conjugating transferrin on the surface of the mesoporous framework, which resulted in enhancement of nanoparticle uptake and drug delivery efficacy in cells that overexpress the transferrin receptor. Similarly, RGD peptides are used to target metastatic cancer cell lines that over-express integrin alphanubeta3. A circular RGD peptide is bound to the surface of MSNs and the endocytosis and cell killing efficacy of camptothecin loaded nanoparticles is significantly improved in cells that express the target receptor. Besides targeting, I studied the ultimate fate of phosphonate coated mesoporous silica nanoparticles inside cells. I discovered that the nanoparticles are exocytosed from cells through lysosomal exocytosis. The nanoparticles are exocytosed in intact form and the time that they remain inside the cells is affected by the surface properties of the nanoparticles and the type of cells. Cells that have a high rate of lysosomal exocytosis excrete the nanoparticles rapidly, which makes them more resistant to drug loaded nanoparticles because the amount of drug that is released inside the cell is limited. When the exocytosis of MSNs is inhibited, the cell killing efficacy of nanoparticles loaded with camptothecin is enhanced. The discovery that MSNs are exocytosed by cells led to a study to determine if proteins could be recovered from the exocytosed nanoparticles. The procedure to isolate exocytosed zinc-doped iron core MSNs and identify the proteins bound to them was developed

  11. Production of biological nanoparticles from bovine serum albumin ...

    African Journals Online (AJOL)

    Production of biological nanoparticles from bovine serum albumin for drug delivery. ... Bovine serum albumin (BSA) was used for generation of nanoparticles in a drug delivery system. ... The impact of protein concentration and additional rate of organic solvent (i.e. ethanol) upon the particle ... AJOL African Journals Online.

  12. Microfluidic Synthesis of Highly Potent Limit-size Lipid Nanoparticles for In Vivo Delivery of siRNA

    Directory of Open Access Journals (Sweden)

    Nathan M Belliveau

    2012-01-01

    Full Text Available Lipid nanoparticles (LNP are the leading systems for in vivo delivery of small interfering RNA (siRNA for therapeutic applications. Formulation of LNP siRNA systems requires rapid mixing of solutions containing cationic lipid with solutions containing siRNA. Current formulation procedures employ macroscopic mixing processes to produce systems 70-nm diameter or larger that have variable siRNA encapsulation efficiency, homogeneity, and reproducibility. Here, we show that microfluidic mixing techniques, which permit millisecond mixing at the nanoliter scale, can reproducibly generate limit size LNP siRNA systems 20 nm and larger with essentially complete encapsulation of siRNA over a wide range of conditions with polydispersity indexes as low as 0.02. Optimized LNP siRNA systems produced by microfluidic mixing achieved 50% target gene silencing in hepatocytes at a dose level of 10 µg/kg siRNA in mice. We anticipate that microfluidic mixing, a precisely controlled and readily scalable technique, will become the preferred method for formulation of LNP siRNA delivery systems.

  13. High-Throughput Quantification of Nanoparticle Degradation Using Computational Microscopy and Its Application to Drug Delivery Nanocapsules

    KAUST Repository

    Ray, Aniruddha

    2017-04-25

    Design and synthesis of degradable nanoparticles are very important in drug delivery and biosensing fields. Although accurate assessment of nanoparticle degradation rate would improve the characterization and optimization of drug delivery vehicles, current methods rely on estimating the size of the particles at discrete points over time using, for example, electron microscopy or dynamic light scattering (DLS), among other techniques, all of which have drawbacks and practical limitations. There is a significant need for a high-throughput and cost-effective technology to accurately monitor nanoparticle degradation as a function of time and using small amounts of sample. To address this need, here we present two different computational imaging-based methods for monitoring and quantification of nanoparticle degradation. The first method is suitable for discrete testing, where a computational holographic microscope is designed to track the size changes of protease-sensitive protein-core nanoparticles following degradation, by periodically sampling a subset of particles mixed with proteases. In the second method, a sandwich structure was utilized to observe, in real-time, the change in the properties of liquid nanolenses that were self-assembled around degrading nanoparticles, permitting continuous monitoring and quantification of the degradation process. These cost-effective holographic imaging based techniques enable high-throughput monitoring of the degradation of any type of nanoparticle, using an extremely small amount of sample volume that is at least 3 orders of magnitude smaller than what is required by, for example, DLS-based techniques.

  14. Transport of magneto-nanoparticles during electro-osmotic flow in a micro-tube in the presence of magnetic field for drug delivery application

    Science.gov (United States)

    Mondal, A.; Shit, G. C.

    2017-11-01

    In this paper, we have examined the motion of magnetic-nanoparticles and the flow characteristics of biofluid in a micro-tube in the presence of externally applied magnetic field and electrokinetic effects. In the drug delivery system, the motion of the magnetic nanoparticles as carriers is important for therapeutic procedure in the treatment of tumor cells, infections and removing blood clots. The unidirectional electro-osmotic flow of biofluid is driven by the combined effects of pulsatile pressure gradient and electrokinetic force. The governing equation for unsteady electromagnetohydrodynamic flow subject to the no-slip boundary condition has been solved numerically by using Crank-Nicolson implicit finite difference scheme. We have analyzed the variation of axial velocity, velocity distribution of magnetic nanoparticles, volumetric flow rate and wall shear stress for various values of the non-dimensional parameters. The study reveals that blood flow velocity, carriers velocity and flow rate are strongly influenced by the electro-osmotic parameter as well as the Hartmann number. The particle mass parameter as well as the particle concentration parameter have efficient capturing effect on magnetic nanoparticles during blood flow through a micro-tube for drug delivery.

  15. D-Glucose as a modifying agent in gelatin/collagen matrix and reservoir nanoparticles for Calendula officinalis delivery.

    Science.gov (United States)

    Lam, P-L; Kok, S H-L; Bian, Z-X; Lam, K-H; Tang, J C-O; Lee, K K-H; Gambari, R; Chui, C-H

    2014-05-01

    Gelatin/Collagen-based matrix and reservoir nanoparticles require crosslinkers to stabilize the formed nanosuspensions, considering that physical instability is the main challenge of nanoparticulate systems. The use of crosslinkers improves the physical integrity of nanoformulations under the-host environment. Aldehyde-based fixatives, such as formaldehyde and glutaraldehyde, have been widely applied to the crosslinking process of polymeric nanoparticles. However, their potential toxicity towards human beings has been demonstrated in many previous studies. In order to tackle this problem, D-glucose was used during nanoparticle formation to stabilize the gelatin/collagen-based matrix wall and reservoir wall for the deliveries of Calendula officinalis powder and oil, respectively. In addition, therapeutic selectivity between malignant and normal cells could be observed. The C. officinalis powder loaded nanoparticles significantly strengthened the anti-cancer effect towards human breast adenocarcinoma MCF7 cells and human hepatoma SKHep1 cells when compared with the free powder. On the contrary, the nanoparticles did not show significant cytotoxicity towards normal esophageal epithelial NE3 cells and human skin keratinocyte HaCaT cells. On the basis of these evidences, D-glucose modified gelatin/collagen matrix nanoparticles containing C. officinalis powder might be proposed as a safer alternative vehicle for anti-cancer treatments. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA

    Directory of Open Access Journals (Sweden)

    Malhotra M

    2013-05-01

    Full Text Available Meenakshi Malhotra,1 Catherine Tomaro-Duchesneau,1 Shyamali Saha,2 Imen Kahouli,3 Satya Prakash11Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, 2Faculty of Dentistry, 3Department of Experimental Medicine, McGill University, Montreal, QC, CanadaAbstract: Recently, cell-penetrating peptides have been proposed to translocate antibodies, proteins, and other molecules in targeted drug delivery. The proposed study presents the synthesis and characterization of a peptide-based chitosan nanoparticle for small interfering RNA (siRNA delivery, in-vitro. Specifically, the synthesis included polyethylene glycol (PEG, a hydrophilic polymer, and trans-activated transcription (TAT peptide, which were chemically conjugated on the chitosan polymer. The conjugation was achieved using N-Hydroxysuccinimide-PEG-maleimide (heterobifunctional PEG as a cross-linker, with the bifunctional PEG facilitating the amidation reaction through its N-Hydroxysuccinimide group and reacting with the amines on chitosan. At the other end of PEG, the maleimide group was chemically conjugated with the cysteine-modified TAT peptide. The degree of substitution on chitosan with PEG and on PEG with TAT was confirmed using colorimetric assays. The resultant polymer was used to form nanoparticles complexing siRNA, which were then characterized for particle size, morphology, cellular uptake, and cytotoxicity. The nanoparticles were tested in-vitro on mouse neuroblastoma cells (Neuro2a. Particle size and surface charge were characterized and an optimal pH condition and PEG molecular weight were determined to form sterically stable nanoparticles. Results indicate 7.5% of the amines in chitosan polymer were conjugated to the PEG and complete conjugation of TAT peptide was observed on the synthesized PEGylated chitosan polymer. Compared with unmodified chitosan nanoparticles, the nanoparticles formed at pH 6 were

  17. Nanoparticle-based delivery of small interfering RNA: challenges for cancer therapy

    Directory of Open Access Journals (Sweden)

    Miele E

    2012-07-01

    Full Text Available Evelina Miele,1,* Gian Paolo Spinelli,2,* Ermanno Miele,3 Enzo Di Fabrizio,3,6 Elisabetta Ferretti,4 Silverio Tomao,2 Alberto Gulino,1,5 1Department of Molecular Medicine, 2Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, 3Nanostructures, Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genova, 4Department of Experimental Medicine, Sapienza University of Rome, Rome, 5Center for Life Nanoscience, Istituto Italiano di Tecnologia, Rome, Italy, 6BIONEM lab, University of Magna Graecia, Campus S. Venuta, Viale Europa 88100 Catanzaro, Italy *These authors contributed equally to this workAbstract: During recent decades there have been remarkable advances and profound changes in cancer therapy. Many therapeutic strategies learned at the bench, including monoclonal antibodies and small molecule inhibitors, have been used at the bedside, leading to important successes. One of the most important advances in biology has been the discovery that small interfering RNA (siRNA is able to regulate the expression of genes, by a phenomenon known as RNA interference (RNAi. RNAi is one of the most rapidly growing fields of research in biology and therapeutics. Much research effort has gone into the application of this new discovery in the treatment of various diseases, including cancer. However, even though these molecules may have potential and strong utility, some limitations make their clinical application difficult, including delivery problems, side effects due to off-target actions, disturbance of physiological functions of the cellular machinery involved in gene silencing, and induction of the innate immune response. Many researchers have attempted to overcome these limitations and to improve the safety of potential RNAi-based therapeutics. Nanoparticles, which are nanostructured entities with tunable size, shape, and surface, as well as biological behavior, provide an ideal opportunity to modify current

  18. Self-assembled silk sericin/poloxamer nanoparticles as nanocarriers of hydrophobic and hydrophilic drugs for targeted delivery

    International Nuclear Information System (INIS)

    Mandal, Biman B; Kundu, S C

    2009-01-01

    In recent times self-assembled micellar nanoparticles have been successfully employed in tissue engineering for targeted drug delivery applications. In this review, silk sericin protein from non-mulberry Antheraea mylitta tropical tasar silk cocoons was blended with pluronic F-127 and F-87 in the presence of solvents to achieve self-assembled micellar nanostructures capable of carrying both hydrophilic (FITC-inulin) and hydrophobic (anticancer drug paclitaxel) drugs. The fabricated nanoparticles were subsequently characterized for their size distribution, drug loading capability, cellular uptake and cytotoxicity. Nanoparticle sizes ranged between 100 and 110 nm in diameter as confirmed by dynamic light scattering. Rapid uptake of these particles into cells was observed in in vitro cellular uptake studies using breast cancer MCF-7 cells. In vitro cytotoxicity assay using paclitaxel-loaded nanoparticles against breast cancer cells showed promising results comparable to free paclitaxel drugs. Drug-encapsulated nanoparticle-induced apoptosis in MCF-7 cells was confirmed by FACS and confocal microscopic studies using Annexin V staining. Up-regulation of pro-apoptotic protein Bax, down-regulation of anti-apoptotic protein Bcl-2 and cleavage of regulatory protein PARP through Western blot analysis suggested further drug-induced apoptosis in cells. This study projects silk sericin protein as an alternative natural biomaterial for fabrication of self-assembled nanoparticles in the presence of poloxamer for successful delivery of both hydrophobic and hydrophilic drugs to target sites.

  19. Self-assembled silk sericin/poloxamer nanoparticles as nanocarriers of hydrophobic and hydrophilic drugs for targeted delivery

    Energy Technology Data Exchange (ETDEWEB)

    Mandal, Biman B; Kundu, S C, E-mail: kundu@hijli.iitkgp.ernet.i [Department of Biotechnology, Indian Institute of Technology, Kharagpur 721302 (India)

    2009-09-02

    In recent times self-assembled micellar nanoparticles have been successfully employed in tissue engineering for targeted drug delivery applications. In this review, silk sericin protein from non-mulberry Antheraea mylitta tropical tasar silk cocoons was blended with pluronic F-127 and F-87 in the presence of solvents to achieve self-assembled micellar nanostructures capable of carrying both hydrophilic (FITC-inulin) and hydrophobic (anticancer drug paclitaxel) drugs. The fabricated nanoparticles were subsequently characterized for their size distribution, drug loading capability, cellular uptake and cytotoxicity. Nanoparticle sizes ranged between 100 and 110 nm in diameter as confirmed by dynamic light scattering. Rapid uptake of these particles into cells was observed in in vitro cellular uptake studies using breast cancer MCF-7 cells. In vitro cytotoxicity assay using paclitaxel-loaded nanoparticles against breast cancer cells showed promising results comparable to free paclitaxel drugs. Drug-encapsulated nanoparticle-induced apoptosis in MCF-7 cells was confirmed by FACS and confocal microscopic studies using Annexin V staining. Up-regulation of pro-apoptotic protein Bax, down-regulation of anti-apoptotic protein Bcl-2 and cleavage of regulatory protein PARP through Western blot analysis suggested further drug-induced apoptosis in cells. This study projects silk sericin protein as an alternative natural biomaterial for fabrication of self-assembled nanoparticles in the presence of poloxamer for successful delivery of both hydrophobic and hydrophilic drugs to target sites.

  20. Simultaneous hyperthermia and doxorubicin delivery from polymer-coated magnetite nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Iglesias, G.R., E-mail: iglesias@ugr.es [Department of Applied Physics, University of Granada, Granada 18071 (Spain); Delgado, A.V.; González-Caballero, F. [Department of Applied Physics, University of Granada, Granada 18071 (Spain); Ramos-Tejada, M.M. [Department of Physics, University of Jaén, Linares 23700 (Spain)

    2017-06-01

    In this work, the hyperthermia response, (i.e., heating induced by an externally applied alternating magnetic field) and the simultaneous release of an anti-cancer drug (doxorubicin) by polymer-coated magnetite nanoparticles have been investigated. After describing the setup for hyperthermia measurements in suspensions of magnetic nanoparticles, the hyperthermia (represented by the rate of suspension heating and, ultimately, by the specific absorption rate or SAR) of magnetite nanoparticles (both bare and polymer-coated as drug nanocarriers) is discussed. The effect of the applied ac magnetic field on doxorubicin release is also studied, and it is concluded that the field does not interfere with the release process, demonstrating the double functionality of the investigated particles. - Highlights: • Magnetite NPs coated with polymers are used for drug delivery and hyperthermia. • The SAR of polyelectrolyte-coated NPs is larger because of their improved stability. • The antitumor drug doxorubicin is adsorbed on the coated particles. • The release rate of the drug is not affected by the ac magnetic field used in hyperthermia.

  1. Exploration of a Doxorubicin-Polymer Conjugate in Lipid-Polymer Hybrid Nanoparticle Drug Delivery

    Science.gov (United States)

    Lough, Emily

    Nanoparticle (NP) drug delivery is a major focus in the research community because of its potential to use existing drugs in safer and more effective ways. Chemotherapy encapsulation in NPs shields the drug from the rest of the body while it is within the NP, with less systemic exposure leading to fewer off-target effects of the drug. However, passive loading of drugs into NPs is a suboptimal method, often leading to burst release upon administration. This work explores the impact of incorporating the drug-polymer conjugate doxorubicin-poly (lactic-co-glycolic) acid (Dox-PLGA) into a lipid-polymer hybrid nanoparticle (LPN). The primary difference in using a drug-polymer conjugate for NP drug delivery is the drug's release kinetics. Dox-PLGA LPNs showed a more sustained and prolonged release profile over 28 days compared to LPNs with passively loaded, unconjugated doxorubicin. This sustained release translates to cytotoxicity; when systemic circulation was simulated using dialysis, Dox-PLGA LPNs retained their cytotoxicity at a higher level than the passively loaded LPNs. The in vivo implication of preserving cytotoxic potency through a slower release profile is that the majority of Dox delivered via Dox-PLGA LPNs will be kept within the LPN until it reaches the tumor. This will result in fewer systemic side effects and more effective treatments given the higher drug concentration at the tumor site. An intriguing clinical application of this drug delivery approach lies in using Dox-PLGA LPNs to cross the blood-brain barrier (BBB). The incorporation of Dox-PLGA is hypothesized to have a protective effect on the BBB as its slow release profile will prevent drug from harming the BBB. Using induced pluripotent stem cells differentiated to human brain microvascular endothelial cells that comprise the BBB, the Dox-PLGA LPNs were shown to be less destructive to the BBB than their passively loaded counterparts. Dox-PLGA LPNs showed superior cytotoxicity against plated tumor

  2. Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement

    Directory of Open Access Journals (Sweden)

    Li CY

    2016-11-01

    Full Text Available ChunYan Li,1 ZhiGang Huang,2 ZheShuo Liu,1 LiQian Ci,3 ZhePeng Liu,3 Yu Liu,2 XueYing Yan,1 WeiYue Lu2 1School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 2Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, 3School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China Abstract: Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050, good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA assay of

  3. Polyphosphoester nanoparticles as biodegradable platform for delivery of multiple drugs and siRNA

    Directory of Open Access Journals (Sweden)

    Elzeny H

    2017-02-01

    Full Text Available Hadeel Elzeny,1,* Fuwu Zhang,2,* Esraa N Ali,1 Heba A Fathi,1 Shiyi Zhang,3 Richen Li,2 Mohamed A El-Mokhtar,4 Mostafa A Hamad,5 Karen L Wooley,2,6 Mahmoud Elsabahy1,6–8 1Assiut International Center of Nanomedicine, Al-Rajhy Liver Hospital, Assiut University, Assiut, Egypt; 2Departments of Chemistry, Chemical Engineering and Materials Science and Engineering, Texas A&M University, College Station, TX, USA; 3School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Microbiology and Immunology, Faculty of Medicine, 5Department of Surgery, Faculty of Medicine, Assiut University, Assiut, Egypt; 6Laboratory for Synthetic-Biologic Interactions, Department of Chemistry, Texas A&M University, College Station, TX, USA; 7Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, 8Misr University for Science and Technology, 6th of October City, Egypt *These authors contributed equally to this work Abstract: Delivery of multiple therapeutics and/or diagnostic agents to diseased tissues is challenging and necessitates the development of multifunctional platforms. Among the various strategies for design of multifunctional nanocarriers, biodegradable polyphosphoester (PPE polymers have been recently synthesized via a rapid and simple synthetic strategy. In addition, the chemical structure of the polymer could be tuned to form nanoparticles with varying surface chemistries and charges, which have shown exceptional safety and biocompatibility as compared to several commercial agents. The purpose of this study was to exploit a mixture of PPE nanoparticles of cationic and neutral surface charges for multiple delivery of anticancer drugs (ie, sorafenib and paclitaxel and nucleic acids (ie, siRNA. Cationic PPE polymers could efficiently complex siRNA, and the stability of the nanoparticles could be maintained in physiological solutions and upon freeze-drying and were able to deliver si

  4. Functionally engineered nanosized particles in pharmaceutics: improved oral delivery of poorly water-soluble drugs.

    Science.gov (United States)

    Ozeki, Tetsuya; Tagami, Tatsuaki

    2013-01-01

    The development of drug nanoparticles has attracted substantial attention because of their potential to improve the dissolution rate and oral availability of poorly water-soluble drugs. This review summarizes the recent articles that discussed nanoparticle-based oral drug delivery systems. The preparation methods were categorized as top-down and bottom-up methods, which are common methods for preparing drug nanoparticles. In addition, methods of handling drug nanoparticles (e.g., one-step preparation of nanocomposites which are microparticles containing drug nanoparticles) were introduced for the effective preservation of drug nanoparticles. The carrier-based preparation of drug nanoparticles was also introduced as a potentially promising oral drug delivery system.

  5. Preparation and characterization of polymer nanocomposites coated magnetic nanoparticles for drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Prabha, G., E-mail: gprabhagovinn@gmail.com; Raj, V., E-mail: alaguraj2@rediffmail.com

    2016-06-15

    In the present research work, the anticancer drug ‘curcumin’ is loaded with Chitosan (CS)-polyethylene glycol (PEG)-polyvinylpyrrolidone (PVP) (CS-PEG-PVP) polymer nanocomposites coated with superparamagnetic iron oxide (Fe{sub 3}O{sub 4}) nanoparticles. The system can be used for targeted and controlled drug delivery of anticancer drugs with reduced side effects and greater efficiency. The prepared nanoparticles were characterized by Fourier transmission infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Curcumin drug loaded Fe{sub 3}O{sub 4}-CS, Fe{sub 3}O{sub 4}-CS-PEG and Fe{sub 3}O{sub 4}-CS-PEG-PVP nanoparticles exhibited the mean particle size in the range of 183–390 nm with a zeta potential value of 26–41 mV as measured using Malvern Zetasizer. The encapsulation efficiency, loading capacity and in-vitro drug release behavior of curcumin drug loaded Fe{sub 3}O{sub 4}-CS, Fe{sub 3}O{sub 4}-CS-PEG and Fe{sub 3}O{sub 4}-CS-PEG-PVP nanoparticles were studied using UV spectrophotometer. Besides, the cytotoxicity of the prepared nanoparticles using MTT assay was also studied. The curcumin drug release was examined at different pH medium and it was proved that the drug release depends upon the pH medium in addition to the nature of matrix. - Highlights: • The considered drug carrier Fe{sub 3}O{sub 4}-CS-PEG-PVP nanoparticles were prepared and entrapping (Curcumin). • The amount of the drug had great effect on the drug LC and EE and zeta potential Nanocomposites. • The Curcumin- loaded Fe{sub 3}O{sub 4}-CS, Fe{sub 3}O{sub 4}-CS-PEG and Fe{sub 3}O{sub 4}-CS-PEG-PVP nanocomposites showed pH responsive drug release.

  6. Preparation and characterization of polymer nanocomposites coated magnetic nanoparticles for drug delivery applications

    International Nuclear Information System (INIS)

    Prabha, G.; Raj, V.

    2016-01-01

    In the present research work, the anticancer drug ‘curcumin’ is loaded with Chitosan (CS)-polyethylene glycol (PEG)-polyvinylpyrrolidone (PVP) (CS-PEG-PVP) polymer nanocomposites coated with superparamagnetic iron oxide (Fe 3 O 4 ) nanoparticles. The system can be used for targeted and controlled drug delivery of anticancer drugs with reduced side effects and greater efficiency. The prepared nanoparticles were characterized by Fourier transmission infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Curcumin drug loaded Fe 3 O 4 -CS, Fe 3 O 4 -CS-PEG and Fe 3 O 4 -CS-PEG-PVP nanoparticles exhibited the mean particle size in the range of 183–390 nm with a zeta potential value of 26–41 mV as measured using Malvern Zetasizer. The encapsulation efficiency, loading capacity and in-vitro drug release behavior of curcumin drug loaded Fe 3 O 4 -CS, Fe 3 O 4 -CS-PEG and Fe 3 O 4 -CS-PEG-PVP nanoparticles were studied using UV spectrophotometer. Besides, the cytotoxicity of the prepared nanoparticles using MTT assay was also studied. The curcumin drug release was examined at different pH medium and it was proved that the drug release depends upon the pH medium in addition to the nature of matrix. - Highlights: • The considered drug carrier Fe 3 O 4 -CS-PEG-PVP nanoparticles were prepared and entrapping (Curcumin). • The amount of the drug had great effect on the drug LC and EE and zeta potential Nanocomposites. • The Curcumin- loaded Fe 3 O 4 -CS, Fe 3 O 4 -CS-PEG and Fe 3 O 4 -CS-PEG-PVP nanocomposites showed pH responsive drug release.

  7. Using DNA nanotechnology to produce a drug delivery system

    Science.gov (United States)

    Huyen La, Thi; Thu Thuy Nguyen, Thi; Phuc Pham, Van; Huyen Nguyen, Thi Minh; Huan Le, Quang

    2013-03-01

    Drug delivery to cancer cells in chemotherapy is one of the most advanced research topics. The effectiveness of the current cancer treatment drugs is limited because they are not capable of distinguishing between cancer cells and normal cells so that they kill not only cancer cells but also normal ones. To overcome this disadvantage by profiting from the differences in physical and chemical properties between cancer and normal cells, nanoparticles (NPs) delivering a drug are designed in a specific manner such that they can distinguish the cancer cells from the normal ones and are targeted only to the cancer cells. Currently, there are various drug delivery systems with many advantages, but sharing some common disadvantages such as difficulty with controlling the size, low encapsulation capacity and low stability. With the development and success of DNA nanotechnology, DNA strands are used to create effective drug delivery NPs with precisely controlled size and structure, safety and high stability. This article presents our study on drug encapsulation in DNA nanostructure which loaded docetaxel and curcumin in a desire to create a new and effective drug delivery system with high biological compatibility. Invited talk at the 6th International Workshop on Advanced Materials Science and Nanotechnology, 30 October-2 November, 2012, Ha Long, Vietnam.

  8. Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection.

    Science.gov (United States)

    Chu, Dafeng; Gao, Jin; Wang, Zhenjia

    2015-12-22

    Endothelial cells form a monolayer in lumen of blood vessels presenting a great barrier for delivery of therapeutic nanoparticles (NPs) into extravascular tissues where most diseases occur, such as inflammation disorders and infection. Here, we report a strategy for delivering therapeutic NPs across this blood vessel barrier by nanoparticle in situ hitchhiking activated neutrophils. Using intravital microscopy of TNF-α-induced inflammation of mouse cremaster venules and a mouse model of acute lung inflammation, we demonstrated that intravenously (iv) infused NPs made from denatured bovine serum albumin (BSA) were specifically internalized by activated neutrophils, and subsequently, the neutrophils containing NPs migrated across blood vessels into inflammatory tissues. When neutrophils were depleted using anti-Gr-1 in a mouse, the transport of albumin NPs across blood vessel walls was robustly abolished. Furthermore, it was found that albumin nanoparticle internalization did not affect neutrophil mobility and functions. Administration of drug-loaded albumin NPs markedly mitigated the lung inflammation induced by LPS (lipopolysaccharide) or infection by Pseudomonas aeruginosa. These results demonstrate the use of an albumin nanoparticle platform for in situ targeting of activated neutrophils for delivery of therapeutics across the blood vessel barriers into diseased sites. This study demonstrates our ability to hijack neutrophils to deliver nanoparticles to targeted diseased sites.

  9. Delivery of disulfiram into breast cancer cells using folate-receptor-targeted PLGA-PEG nanoparticles: in vitro and in vivo investigations.

    Science.gov (United States)

    Fasehee, Hamidreza; Dinarvand, Rassoul; Ghavamzadeh, Ardeshir; Esfandyari-Manesh, Mehdi; Moradian, Hanieh; Faghihi, Shahab; Ghaffari, Seyed Hamidollah

    2016-04-21

    A folate-receptor-targeted poly (lactide-co-Glycolide) (PLGA)-Polyethylene glycol (PEG) nanoparticle is developed for encapsulation and delivery of disulfiram into breast cancer cells. After a comprehensive characterization of nanoparticles, cell cytotoxicity, apoptosis induction, cellular uptake and intracellular level of reactive oxygen species are analyzed. In vivo acute and chronic toxicity of nanoparticles and their efficacy on inhibition of breast cancer tumor growth is studied. The folate-receptor-targeted nanoparticles are internalized into the cells, induce reactive oxygen species formation, induce apoptosis and inhibit cell proliferation more efficiently compared to the untargeted nanoparticles. The acute and toxicity test show the maximum dose of disulfiram equivalent of nanoparticles for intra-venous injection is 6 mg/kg while show significant decrease in the breast cancer tumor growth rate. It is believed that the developed formulation could be used as a potential vehicle for successful delivery of disulfiram, an old and inexpensive drug, into breast cancer cells and other solid tumors.

  10. Application of nanohydrogels in drug delivery systems: recent patents review.

    Science.gov (United States)

    Dalwadi, Chintan; Patel, Gayatri

    2015-01-01

    Nanohydrogel combines the advantages of hydrogel and nano particulate systems. Similar to the hydrogel and macrogel, nanohydrogel can protect the drug and control drug release by stimuli responsive conformation or biodegradable bond into the polymer networks. Nanohydrogel has drawn huge interest due to their potential applications, such as carrier in target-specific controlled drug delivery, absorbents, chemical/biological sensors, and bio-mimetic materials. Similar to the nanoparticles, stimuli responsive nanohydrogel can easily be delivered in the liquid form for parenteral drug delivery application. This review highlights the methods to prepare nanohydrogel based on natural and synthetic polymers for diverse applications in drug delivery. It also encompasses the drug loading and drug release mechanism of the nanohydrogel formulation and patents related to the composition and chemical methods for preparation of nanohydrogel formulation with current status in clinical trials.

  11. Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells

    Directory of Open Access Journals (Sweden)

    Sharma Kamal

    2008-12-01

    Full Text Available Abstract Background Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells. Methods Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured in vivo with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed ex vivo with fluorescence imaging. Results We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells. Conclusion The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives.

  12. Seaweed Polysaccharide-Based Nanoparticles: Preparation and Applications for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Jayachandran Venkatesan

    2016-01-01

    Full Text Available In recent years, there have been major advances and increasing amounts of research on the utilization of natural polymeric materials as drug delivery vehicles due to their biocompatibility and biodegradability. Seaweed polysaccharides are abundant resources and have been extensively studied for several biological, biomedical, and functional food applications. The exploration of seaweed polysaccharides for drug delivery applications is still in its infancy. Alginate, carrageenan, fucoidan, ulvan, and laminarin are polysaccharides commonly isolated from seaweed. These natural polymers can be converted into nanoparticles (NPs by different types of methods, such as ionic gelation, emulsion, and polyelectrolyte complexing. Ionic gelation and polyelectrolyte complexing are commonly employed by adding cationic molecules to these anionic polymers to produce NPs of a desired shape, size, and charge. In the present review, we have discussed the preparation of seaweed polysaccharide-based NPs using different types of methods as well as their usage as carriers for the delivery of various therapeutic molecules (e.g., proteins, peptides, anti-cancer drugs, and antibiotics. Seaweed polysaccharide-based NPs exhibit suitable particle size, high drug encapsulation, and sustained drug release with high biocompatibility, thereby demonstrating their high potential for safe and efficient drug delivery.

  13. Amphiphilic poly{[α-maleic anhydride-ω-methoxypoly(ethylene glycol]-co-(ethyl cyanoacrylate} graft copolymer nanoparticles as carriers for transdermal drug delivery

    Directory of Open Access Journals (Sweden)

    Jinfeng Xing

    2009-10-01

    Full Text Available Jinfeng Xing, Liandong Deng, Jun Li, Anjie DongDepartment of Polymer Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, People’s Republic of ChinaAbstract: In this study, the transdermal drug delivery properties of D,L-tetrahydropalmatine (THP-loaded amphiphilic poly{[α-maleic anhydride-ω-methoxy-poly(ethylene glycol]-co-(ethyl cyanoacrylate} (PEGECA graft copolymer nanoparticles (PEGECAT NPs were evaluated by skin penetration experiments in vitro. The transdermal permeation experiments in vitro were carried out in Franz diffusion cells using THP-loaded PEGECAT NPs as the donor system. Transmission electron microscopy and Fourier transform infrared spectroscopy were used to characterize the receptor fluid. The results indicate that the THP-loaded PEGECAT NPs are able to penetrate the rat skin. Fluorescent microscopy measurements demonstrate that THP-loaded PEGECAT NPs can penetrate the skin not only via appendage routes but also via epidermal routes. This nanotechnology has potential application in transdermal drug delivery. Keywords: poly{[α-maleic anhydride-ω-methoxy-poly(ethylene glycol]-co-(ethyl cyanoacrylate}, nanoparticles, transdermal drug delivery, D,L-tetrahydropalmatine

  14. Effect of tween 80 on nanoparticle preparation of modified chitosan for targeted delivery of combination doxorubicin and curcumin analogue

    Science.gov (United States)

    Sukmawati, Anita; Utami, Wahyu; Yuliani, Ratna; Da'i, Muhammad; Nafarin, Akhmad

    2018-02-01

    Delivery of anticancer is facing several problems including unspecific delivery of active substance to the targeted cell. The conjugation between chitosan and folate (chitosan-FA) was used for nanoparticle preparation containing combination of doxorubicin (DOX) and curcumin analogue, 2,5-bis-(4-hydroxi,3,5-dimethyl)-benzylidincylopentanone, as active substances. The purpose of this research is investigating formulation aspect for chitosan-FA nanoparticle by addition various tween 80 to achieve desired nano-size particle. The ionic gelation method was used for nanoparticle preparation using 0.05% w/v chitosan-FA with addition of 0.1 and 0.5% v/v of tween 80. The result showed that the high concentration of tween 80 during nanoparticle preparation lead to formation of smaller size particle. The 111.8 ±4.11 nm particle size was revealed by addition of 0.5% v/v tween 80 during chitosan-FA nanoparticle preparation loaded with active substances.

  15. Drug permeability and mucoadhesion properties of thiolated trimethyl chitosan nanoparticles in oral insulin delivery.

    Science.gov (United States)

    Yin, Lichen; Ding, Jieying; He, Chunbai; Cui, Liming; Tang, Cui; Yin, Chunhua

    2009-10-01

    Trimethyl chitosan-cysteine conjugate (TMC-Cys) was synthesized in an attempt to combine the mucoadhesion and the permeation enhancing effects of TMC and thiolated polymers related to different mechanisms for oral absorption. TMC-Cys with various molecular weights (30, 200, and 500 kDa) and quaternization degrees (15 and 30%) was allowed to form polyelectrolyte nanoparticles with insulin through self-assembly, which demonstrated particle size of 100-200 nm, zeta potential of +12 to +18 mV, and high encapsulation efficiency. TMC-Cys/insulin nanoparticles (TMC-Cys NP) showed a 2.1-4.7-fold increase in mucoadhesion compared to TMC/insulin nanoparticles (TMC NP), which might be partly attributed to disulfide formation between TMC-Cys and mucin as evidenced by DSC measurement. Compared to insulin solution and TMC NP, TMC-Cys NP induced increased insulin transport through rat intestine by 3.3-11.7 and 1.7-2.6 folds, promoted Caco-2 cell internalization by 7.5-12.7 and 1.7-3.0 folds, and augmented uptake in Peyer's patches by 14.7-20.9 and 1.7-5.0 folds, respectively. Such results were further confirmed by in vivo experiment with the optimal TMC-Cys NP. Biocompatibility assessment revealed lack of toxicity of TMC-Cys NP. Therefore, self-assembled nanoparticles between TMC-Cys and protein drugs could be an effective and safe oral delivery system.

  16. Surface delivery of a single nanoparticle under moving evanescent standing-wave illumination

    Czech Academy of Sciences Publication Activity Database

    Šiler, Martin; Čižmár, Tomáš; Jonáš, Alexandr; Zemánek, Pavel

    2008-01-01

    Roč. 10, č. 11 (2008), 113010: 1-16 ISSN 1367-2630 R&D Projects: GA MŠk(CZ) LC06007; GA MŠk OC08034 Institutional research plan: CEZ:AV0Z20650511 Keywords : nanoparticle * evanescent field * standing-wave illumination * surface delivery Subject RIV: BH - Optics, Masers, Lasers Impact factor: 3.440, year: 2008

  17. Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy.

    Science.gov (United States)

    Liang, Po-Chin; Chen, Yung-Chu; Chiang, Chi-Feng; Mo, Lein-Ray; Wei, Shwu-Yuan; Hsieh, Wen-Yuan; Lin, Win-Li

    2016-01-01

    In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe3O4 core and a shell of aqueous stable polyethylene glycol (PEG) conjugated with doxorubicin (Dox) (SPIO-PEG-D) for tumor magnetic resonance imaging (MRI) enhancement and chemotherapy. The size of SPIO nanoparticles was ~10 nm, which was visualized by transmission electron microscope. The hysteresis curve, generated with vibrating-sample magnetometer, showed that SPIO-PEG-D was superparamagnetic with an insignificant hysteresis. The transverse relaxivity (r 2) for SPIO-PEG-D was significantly higher than the longitudinal relaxivity (r 1) (r 2/r 1 >10). The half-life of Dox in blood circulation was prolonged by conjugating Dox on the surface of SPIO with PEG to reduce its degradation. The in vitro experiment showed that SPIO-PEG-D could cause DNA crosslink more serious, resulting in a lower DNA expression and a higher cell apoptosis for HT-29 cancer cells. The Prussian blue staining study showed that the tumors treated with SPIO-PEG-D under a magnetic field had a much higher intratumoral iron density than the tumors treated with SPIO-PEG-D alone. The in vivo MRI study showed that the T2-weighted signal enhancement was stronger for the group under a magnetic field, indicating that it had a better accumulation of SPIO-PEG-D in tumor tissues. In the anticancer efficiency study for SPIO-PEG-D, the results showed that there was a significantly smaller tumor size for the group with a magnetic field than the group without. The in vivo experiments also showed that this drug delivery system combined with a local magnetic field could reduce the side effects of cardiotoxicity and hepatotoxicity. The results showed that the developed SPIO-PEG-D nanoparticles own a great potential for MRI-monitoring magnet-enhancing tumor chemotherapy.

  18. Formulation of Stable and Homogeneous Cell-Penetrating Peptide NF55 Nanoparticles for Efficient Gene Delivery In Vivo

    Directory of Open Access Journals (Sweden)

    Krista Freimann

    2018-03-01

    Full Text Available Although advances in genomics and experimental gene therapy have opened new possibilities for treating otherwise incurable diseases, the transduction of nucleic acids into the cells and delivery in vivo remain challenging. The high molecular weight and anionic nature of nucleic acids require their packing into nanoparticles for the delivery. The efficacy of nanoparticle drugs necessitates the high bioactivity of constituents, but their distribution in organisms is mostly governed by the physical properties of nanoparticles, and therefore, generation of stable particles with strictly defined characteristics is highly essential. Using previously designed efficient cell-penetrating peptide NF55, we searched for strategies enabling control over the nanoparticle formation and properties to further improve transfection efficacy. The size of the NF55/pDNA nanoparticles correlates with the concentration of its constituents at the beginning of assembly, but characteristics of nanoparticles measured by DLS do not reliably predict the applicability of particles in in vivo studies. We introduce a new formulation approach called cryo-concentration, where we acquired stable and homogeneous nanoparticles for administration in vivo. The cryo-concentrated NF55/pDNA nanoparticles exhibit several advantages over standard formulation: They have long shelf-life and do not aggregate after reconstitution, have excellent stability against enzymatic degradation, and show significantly higher bioactivity in vivo.

  19. Targeted delivery of doxorubicin-utilizing chitosan nanoparticles surface-functionalized with anti-Her2 trastuzumab

    Directory of Open Access Journals (Sweden)

    Yousefpour P

    2011-09-01

    Full Text Available Parisa Yousefpour1, Fatemeh Atyabi2, Ebrahim Vasheghani-Farahani3, Ali-Akbar Mousavi Movahedi1, Rassoul Dinarvand21Department of Biotechnology, Faculty of Science, University of Tehran, 2Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, 3Biotechnology Group, Department of Chemical Engineering, Faculty of Engineering, Tarbiat Modares University, Tehran, IranBackground: Targeting drugs to their sites of action to overcome the systemic side effects associated with most antineoplastic agents is still a major challenge in pharmaceutical research. In this study, the monoclonal antibody, trastuzumab, was used as a targeting agent in nanoparticles carrying the antitumor drug, doxorubicin, specifically to its site of action.Methods: Chitosan-doxorubicin conjugation was carried out using succinic anhydride as a crosslinker. Trastuzumab was conjugated to self-assembled chitosan-doxorubin conjugate (CS-DOX nanoparticles (particle size, 200 nm via thiolation of lysine residues and subsequent linking of the resulted thiols to chitosan. Conjugation was confirmed by gel permeation chromatography, differential scanning calorimetry, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance spectroscopy studies. Dynamic light scattering, transmission electron microscopy, and zeta potential determination were used to characterize the nanoparticles.Results: CS-DOX conjugated nanoparticles had a spherical shape and smooth surface with a narrow size distribution and core-shell structure. Increasing the ratio of doxorubicin to chitosan in the conjugation reaction gave rise to a higher doxorubicin content but lower conjugation efficiency. Trastuzumab-decorated nanoparticles (CS-DOX-mAb contained 47 µg/mg doxorubicin and 33.5 µg/mg trastuzumab. Binding of trastuzumab to the nanoparticles was further probed thermodynamically by isothermal titration calorimetry. Fluorescence microscopy demonstrated enhanced and

  20. Biodegradable nanoparticles for gene therapy technology

    International Nuclear Information System (INIS)

    Hosseinkhani, Hossein; He, Wen-Jie; Chiang, Chiao-Hsi; Hong, Po-Da; Yu, Dah-Shyong; Domb, Abraham J.; Ou, Keng-Liang

    2013-01-01

    Rapid propagations in materials technology together with biology have initiated great hopes in the possibility of treating many diseases by gene therapy technology. Viral and non-viral gene carriers are currently applied for gene delivery. Non-viral technology is safe and effective for the delivery of genetic materials to cells and tissues. Non-viral systems are based on plasmid expression containing a gene encoding a therapeutic protein and synthetic biodegradable nanoparticles as a safe carrier of gene. Biodegradable nanoparticles have shown great interest in drug and gene delivery systems as they are easy to be synthesized and have no side effect in cells and tissues. This review provides a critical view of applications of biodegradable nanoparticles on gene therapy technology to enhance the localization of in vitro and in vivo and improve the function of administered genes

  1. Development and optimization of methotrexate-loaded lipid-polymer hybrid nanoparticles for controlled drug delivery applications.

    Science.gov (United States)

    Tahir, Nayab; Madni, Asadullah; Balasubramanian, Vimalkumar; Rehman, Mubashar; Correia, Alexandra; Kashif, Prince Muhammad; Mäkilä, Ermei; Salonen, Jarno; Santos, Hélder A

    2017-11-25

    Lipid-polymer hybrid nanoparticles (LPHNPs) are emerging platforms for drug delivery applications. In the present study, methotrexate loaded LPHNPs consisted of PLGA and Lipoid S100 were fabricated by employing a single-step modified nanoprecipitation method combined with self-assembly. A three factor, three level Box Behnken design using Design-Expert ® software was employed to access the influence of three independent variables on the particle size, drug entrapment and percent drug release. The optimized formulation was selected through numeric optimization approach. The results were supported with the ANOVA analysis, regression equations and response surface plots. Transmission electron microscope images indicated the nanosized and spherical shape of the LPHNPs with fair size distribution. The nanoparticles ranged from 176 to 308nm, which increased with increased polymer concentration. The increase in polymer and lipid concentration also increased the drug entrapment efficiency. The in vitro drug release was in range 70.34-91.95% and the release mechanism follow the Higuchi model (R 2 =0.9888) and Fickian diffusion (n<0.5). The in vitro cytotoxicity assay and confocal microscopy of the optimized formulation demonstrate the good safety and better internalization of the LPHNPs. The cell antiproliferation showed the spatial and controlled action of the nanoformulation as compared to the plain drug solution. The results suggest that LPHNPs can be a promising delivery system envisioned to safe, stable and potentially controlled delivery of methotrexate to the cancer cells to achieve better therapeutic outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Intelligent layered nanoflare: ``lab-on-a-nanoparticle'' for multiple DNA logic gate operations and efficient intracellular delivery

    Science.gov (United States)

    Yang, Bin; Zhang, Xiao-Bing; Kang, Li-Ping; Huang, Zhi-Mei; Shen, Guo-Li; Yu, Ru-Qin; Tan, Weihong

    2014-07-01

    DNA strand displacement cascades have been engineered to construct various fascinating DNA circuits. However, biological applications are limited by the insufficient cellular internalization of naked DNA structures, as well as the separated multicomponent feature. In this work, these problems are addressed by the development of a novel DNA nanodevice, termed intelligent layered nanoflare, which integrates DNA computing at the nanoscale, via the self-assembly of DNA flares on a single gold nanoparticle. As a ``lab-on-a-nanoparticle'', the intelligent layered nanoflare could be engineered to perform a variety of Boolean logic gate operations, including three basic logic gates, one three-input AND gate, and two complex logic operations, in a digital non-leaky way. In addition, the layered nanoflare can serve as a programmable strategy to sequentially tune the size of nanoparticles, as well as a new fingerprint spectrum technique for intelligent multiplex biosensing. More importantly, the nanoflare developed here can also act as a single entity for intracellular DNA logic gate delivery, without the need of commercial transfection agents or other auxiliary carriers. By incorporating DNA circuits on nanoparticles, the presented layered nanoflare will broaden the applications of DNA circuits in biological systems, and facilitate the development of DNA nanotechnology.DNA strand displacement cascades have been engineered to construct various fascinating DNA circuits. However, biological applications are limited by the insufficient cellular internalization of naked DNA structures, as well as the separated multicomponent feature. In this work, these problems are addressed by the development of a novel DNA nanodevice, termed intelligent layered nanoflare, which integrates DNA computing at the nanoscale, via the self-assembly of DNA flares on a single gold nanoparticle. As a ``lab-on-a-nanoparticle'', the intelligent layered nanoflare could be engineered to perform a variety of

  3. Cotransporting Ion is a Trigger for Cellular Endocytosis of Transporter-Targeting Nanoparticles: A Case Study of High-Efficiency SLC22A5 (OCTN2)-Mediated Carnitine-Conjugated Nanoparticles for Oral Delivery of Therapeutic Drugs.

    Science.gov (United States)

    Kou, Longfa; Yao, Qing; Sun, Mengchi; Wu, Chunnuan; Wang, Jia; Luo, Qiuhua; Wang, Gang; Du, Yuqian; Fu, Qiang; Wang, Jian; He, Zhonggui; Ganapathy, Vadivel; Sun, Jin

    2017-09-01

    OCTN2 (SLC22A5) is a Na + -coupled absorption transporter for l-carnitine in small intestine. This study tests the potential of this transporter for oral delivery of therapeutic drugs encapsulated in l-carnitine-conjugated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (LC-PLGA NPs) and discloses the molecular mechanism for cellular endocytosis of transporter-targeting nanoparticles. Conjugation of l-carnitine to a surface of PLGA-NPs enhances the cellular uptake and intestinal absorption of encapsulated drug. In both cases, the uptake process is dependent on cotransporting ion Na + . Computational OCTN2 docking analysis shows that the presence of Na + is important for the formation of the energetically stable intermediate complex of transporter-Na + -LC-PLGA NPs, which is also the first step in cellular endocytosis of nanoparticles. The transporter-mediated intestinal absorption of LC-PLGA NPs occurs via endocytosis/transcytosis rather than via the traditional transmembrane transport. The portal blood versus the lymphatic route is evaluated by the plasma appearance of the drug in the control and lymph duct-ligated rats. Absorption via the lymphatic system is the predominant route in the oral delivery of the NPs. In summary, LC-PLGA NPs can effectively target OCTN2 on the enterocytes for enhancing oral delivery of drugs and the critical role of cotransporting ions should be noticed in designing transporter-targeting nanoparticles. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Food-grade protein-based nanoparticles and microparticles for bioactive delivery: fabrication, characterization, and utilization.

    Science.gov (United States)

    Davidov-Pardo, Gabriel; Joye, Iris J; McClements, David Julian

    2015-01-01

    Proteins can be used to fabricate nanoparticles and microparticles suitable for use as delivery systems for bioactive compounds in pharmaceutical, food, cosmetic, and other products. Food proteins originate from various animal or vegetal sources and exhibit a wide diversity of molecular and physicochemical characteristics, e.g., molecular weight, conformation, flexibility, polarity, charge, isoelectric point, solubility, and interactions. As a result, protein particles can be assembled using numerous different preparation methods, from one or more types of protein or from a combination of a protein and another type of biopolymer (usually a polysaccharide). The final characteristics of the particles produced are determined by the proteins and/or polysaccharides used, as well as the fabrication techniques employed. This chapter provides an overview of the functional properties of food proteins that can be used to assemble nanoparticles and microparticles, the fabrication techniques available to create those particles, the factors that influence their stability, and their potential applications within the food industry. © 2015 Elsevier Inc. All rights reserved.

  5. The effects of collagen-rich extracellular matrix on the intracellular delivery of glycol chitosan nanoparticles in human lung fibroblasts.

    Science.gov (United States)

    Yhee, Ji Young; Yoon, Hong Yeol; Kim, Hyunjoon; Jeon, Sangmin; Hergert, Polla; Im, Jintaek; Panyam, Jayanth; Kim, Kwangmeyung; Nho, Richard Seonghun

    2017-01-01

    Recent progress in nanomedicine has shown a strong possibility of targeted therapy for obstinate chronic lung diseases including idiopathic pulmonary fibrosis (IPF). IPF is a fatal lung disease characterized by persistent fibrotic fibroblasts in response to type I collagen-rich extracellular matrix. As a pathological microenvironment is important in understanding the biological behavior of nanoparticles, in vitro cellular uptake of glycol chitosan nanoparticles (CNPs) in human lung fibroblasts was comparatively studied in the presence or absence of type I collagen matrix. Primary human lung fibroblasts from non-IPF and IPF patients (n=6/group) showed significantly increased cellular uptake of CNPs (>33.6-78.1 times) when they were cultured on collagen matrix. To elucidate the underlying mechanism of enhanced cellular delivery of CNPs in lung fibroblasts on collagen, cells were pretreated with chlorpromazine, genistein, and amiloride to inhibit clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis, respectively. Amiloride pretreatment remarkably reduced the cellular uptake of CNPs, suggesting that lung fibroblasts mainly utilize the macropinocytosis-dependent mechanism when interacted with collagen. In addition, the internalization of CNPs was predominantly suppressed by a phosphoinositide 3-kinase (PI3K) inhibitor in IPF fibroblasts, indicating that enhanced PI3K activity associated with late-stage macropinocytosis can be particularly important for the enhanced cellular delivery of CNPs in IPF fibroblasts. Our study strongly supports the concept that a pathological microenvironment which surrounds lung fibroblasts has a significant impact on the intracellular delivery of nanoparticles. Based on the property of enhanced intracellular delivery of CNPs when fibroblasts are made to interact with a collagen-rich matrix, we suggest that CNPs may have great potential as a drug-carrier system for targeting fibrotic lung fibroblasts.

  6. Biodistribution and pharmacokinetics of dapivirine-loaded nanoparticles after vaginal delivery in mice.

    Science.gov (United States)

    das Neves, José; Araújo, Francisca; Andrade, Fernanda; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

    2014-07-01

    To assess the potential of polymeric nanoparticles (NPs) to affect the genital distribution and local and systemic pharmacokinetics (PK) of the anti-HIV microbicide drug candidate dapivirine after vaginal delivery. Dapivirine-loaded, poly(ethylene oxide)-coated poly(epsilon-caprolactone) (PEO-PCL) NPs were prepared by a nanoprecipitation method. Genital distribution of NPs and their ability to modify the PK of dapivirine up to 24 h was assessed after vaginal instillation in a female mouse model. Also, the safety of NPs upon daily administration for 14 days was assessed by histological analysis and chemokine/cytokine content in vaginal lavages. PEO-PCL NPs (180-200 nm) were rapidly eliminated after administration but able to distribute throughout the vagina and lower uterus, and capable of tackling mucus and penetrate the epithelial lining. Nanocarriers modified the PK of dapivirine, with higher drug levels being recovered from vaginal lavages and vaginal/lower uterine tissues as compared to a drug suspension. Systemic drug exposure was reduced when NPs were used. Also, NPs were shown safe upon administration for 14 days. Dapivirine-loaded PEO-PCL NPs were able to provide likely favorable genital drug levels, thus attesting the potential value of using this vaginal drug delivery nanosystem in the context of HIV prophylaxis.

  7. Poly(lactic-co-glycolic) acid drug delivery systems through transdermal pathway: an overview.

    Science.gov (United States)

    Naves, Lucas; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram; Soares, Graça

    2017-05-01

    In past few decades, scientists have made tremendous advancement in the field of drug delivery systems (DDS), through transdermal pathway, as the skin represents a ready and large surface area for delivering drugs. Efforts are in progress to design efficient transdermal DDS that support sustained drug release at the targeted area for longer duration in the recommended therapeutic window without producing side-effects. Poly(lactic-co-glycolic acid) (PLGA) is one of the most promising Food and Drug Administration approved synthetic polymers in designing versatile drug delivery carriers for different drug administration routes, including transdermal drug delivery. The present review provides a brief introduction over the transdermal drug delivery and PLGA as a material in context to its role in designing drug delivery vehicles. Attempts are made to compile literatures over PLGA-based drug delivery vehicles, including microneedles, nanoparticles, and nanofibers and their role in transdermal drug delivery of different therapeutic agents. Different nanostructure evaluation techniques with their working principles are briefly explained.

  8. Cyclic hexapeptide-conjugated nanoparticles enhance curcumin delivery to glioma tumor cells and tissue

    Directory of Open Access Journals (Sweden)

    Zhang X

    2017-08-01

    Full Text Available Xuemei Zhang,1–3 Xuejuan Li,1,4 Hongchen Hua,1 Aiping Wang,1 Wanhui Liu,1–3 Youxin Li,1–3 Fenghua Fu,1–3 Yanan Shi,5 Kaoxiang Sun1 1School of Pharmacy, Yantai University, Yantai, Shandong Province, People’s Republic of China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, Shandong Province, People’s Republic of China; 3Luye Pharmaceutical Co., Ltd., Shandong Province, People’s Republic of China; 4National Engineering and Technology Research Center of Chirality Pharmaceutical, Lunan Pharmaceutical Group Co., Ltd., Shandong Province, People’s Republic of China; 5School of Pharmacy, Binzhou Medical University, Shandong Province, People’s Republic of China Abstract: Glioma has one of the highest mortality rates among primary brain tumors. The clinical treatment for glioma is very difficult due to its infiltration and specific growth locations. To achieve improved drug delivery to a brain tumor, we report the preparation and in vitro and in vivo evaluation of curcumin nanoparticles (Cur-NPs. The cyclic hexapeptide c(RGDf(N-meVK-C (cHP has increased affinity for cells that overexpress integrins and was designed to target Cur-NPs to tumors. Functional polyethyleneglycol-modified poly(D,L-lactide-co-glycolide (PEG-PLGA conjugated to cHP was synthesized, and targeted Cur-NPs were prepared using a self-assembly nanoprecipitation process. The physicochemical properties and the in vitro cytotoxicity, accuracy, and penetration capabilities of Cur-NPs targeting cells with high levels of integrin expression were investigated. The in vivo targeting and penetration capabilities of the NPs were also evaluated against glioma in rats using in vivo imaging equipment. The results showed that the in vitro cytotoxicity of the targeted cHP-modified curcumin nanoparticles (cHP/Cur-NPs was higher than that of either free curcumin or non-targeted Cur-NPs due to the superior ability of the cHP/Cur-NPs to target tumor cells

  9. A novel high drug loading mussel-inspired polydopamine hybrid nanoparticle as a pH-sensitive vehicle for drug delivery.

    Science.gov (United States)

    Hou, Jie; Guo, Chunlei; Shi, Yuzhi; Liu, Ergang; Dong, Weibing; Yu, Bo; Liu, Shiyuan; Gong, Junbo

    2017-11-25

    A novel high drug loading pH-cleavable polymer hybrid nanoparticle was prepared via doxorubicin (DOX) grafted onto PEGylated, mussel-inspired polydopamine (PDA) and then coated onto hollow silica nanoparticles for drug delivery. A series of characterization shed light on the formation mechanisms of PDA coatings on hollow silica. We hypothesized that dopamine was first absorbed onto the surface of hollow silica and then began self-polymerization. A Dox-containing thiol moiety was fabricated with conjugation between doxorubicin hydrochloride and Mercaptopropionyalkali with a pH-cleavable hydrozone bond. Using a Michael addition reaction, several Dox-containing thiol moieties were grafted onto the surface of the PDA. The drug loading capacity can reach 35.43%. It can minimize the metabolic problem of silica. The released behavior of Dox can be significantly enhanced at endosomal pH compared to physiological pH. After folate modification, nanoparticles can lead to more cellular endocytosis. Meanwhile animal assays showed that more Dox accumulated in tumor tissue, which can enhanced the cytotoxicity to 4T1 cancer cells with a targeting group compared to free DOX and untargeted groups. Meanwhile, the tumor growth was significantly inhibited. This promising material shows a promising future as a drug delivery system. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. In-vitro and in-vivo assessment of dextran-appended cellulose acetate phthalate nanoparticles for transdermal delivery of 5-fluorouracil.

    Science.gov (United States)

    Garg, Ashish; Rai, Gopal; Lodhi, Santram; Jain, Alok P; Yadav, Awesh K

    2016-06-01

    The aim of this research was transdermal delivery of 5-fluorouracil (5-FU) using dextran-coated cellulose acetate phthalate (CAP) nanoparticulate formulation. CAP nanoparticles were prepared using drug-polymer ratio (1:1 to 1:3) and surfactant ratio (2.5, 5 and 10%). Dextran coating was made using aminodextran. The results showed that the optimized CAP nanoparticles (CNs) and dextran-coated CAP nanoparticles represented core-corona nanoparticles with the mean diameter of 75 ± 3 and 79 ± 2 nm, respectively, and entrapment efficiency was 82.5 ± 0.06 and 78.2 ± 0.12, respectively. Dextran-coated nanoparticles (FDCNs) and CAP nanoparticles (FCNs) showed in vitro 5-FU release upto 31 h and 8 h, respectively. Moreover, the cumulative amount of 5-FU penetrated through excised skin from FDCNs was 2.94 folds than that of the FU cream. Concentration of 5-FU in epidermis and dermis were also studied. In dermis, concentration of 5-FU was found higher in case of FDCN formulation than plain FU cream. FDCNs were found more hemocompatible in comparison to FCNs. The hematological data recommended that FDCNs formulation was less immunogenic compared to FU creams formulation. In blood level study, FDCNs exhibited 153, 12, 16.66 and 16.24-fold higher values for area under the curve, Tmax, Cmax and mean residence time (MRT) compared with those of FU cream, respectively. The in-vitro cytotoxicity was assessed using the MCF-7 by the MTT test and was compared to the plain 5-FU solution. All the detailed evidence showed that FDCNs could provide a promising tuning as a transdermal delivery system of 5-FU.

  11. Polybutylcyanoacrylate nanoparticles for the delivery of [75Se]norcholestenol

    International Nuclear Information System (INIS)

    Kreuter, J.; Wilson, C.G.

    1983-01-01

    Polybutylcyanoacrylate nanoparticles have been used for the intravenous and intramuscular administration of a steroidal material ([ 75 Se]norcholestenol) to the rabbit. Whole body profiles of 75 Se, obtained using a gamma camera over a period of 30 days, show that the [ 75 Se]norcholestenol is retained for a longer period of time with the nanoparticle system than for the control system where the drug was dissolved in a micellar system. In vitro dialysis experiments indicate that the thermodynamic activity of the drug can be increased by its incorporation within nanoparticles. This increased activity may affect the distribution of the drug into body tissues. (Auth.)

  12. Knock-down of ELMO1 in Paediatric Rhabdomyosarcoma Cells by Nanoparticle Mediated siRNA Delivery

    Directory of Open Access Journals (Sweden)

    Xinyue Huang

    2016-03-01

    Full Text Available Rhabdomyosarcoma (RMS is the most common soft tissue sarcoma that is found in children and has a poor outcome for those with metastatic disease. Two histological groups have been distinguished - embryonal (ERMS and alveolar (ARMS forms. The ARMS subtype has higher rates of metastasis, as well as higher levels of ELMO1, which is thought to be involved in cell migration. Therefore, the knock-down of ELMO1 by targeted siRNA could provide a mechanism to prevent the metastatic behaviour of ARMS cells. However, challenges still lie in the delivery of nucleotides to a tumour site. Herein, we have described the use of a variety of mesoporous silica nanoparticles as a delivery system for siRNA that is specific for ELMO1 and shown the effective reduction in cell invasive behaviour in these cells.

  13. Advances in research of targeting delivery and controlled release of drug-loaded nanoparticles

    International Nuclear Information System (INIS)

    Tan Zhonghua

    2003-01-01

    Biochemistry drug, at present, is still the main tool that human struggle to defeat the diseases. So, developing safe and efficacious technique of drug targeting delivery and controlled release is key to enhance curative effect, decrease drug dosage, and lessen its side effect. Drug-loaded nanoparticles, which is formed by conjugate between nanotechnology and modern pharmaceutics, is a new fashioned pharmic delivery carrier. Because of advantages in pharmic targeting transport and controlled or slow release and improving bioavailability, it has been one of developing trend of modern pharmaceutical dosage forms

  14. Bioactivity of noble metal nanoparticles decorated with biopolymers and their application in drug delivery.

    Science.gov (United States)

    Rai, Mahendra; Ingle, Avinash P; Gupta, Indarchand; Brandelli, Adriano

    2015-12-30

    The unique properties of nanomaterials can be applied to solve different problems including new ways of drug delivery. Noble metal nanoparticles are most promising because they have been used for medicinal purposes since ancient time. It is evident from the past studies that the metallic nanoparticles are much more effective against various microorganisms when compared to their conventional counterparts. However, decoration of such nanoparticles with biomaterials add more advantages to their antimicrobial activity. Decoration of metal nanoparticles with biopolymers is a quite new area of research. Studies performed hitherto shown that nanoparticles of noble metals like silver, gold and platinum demonstrated better antibacterial, antifungal and antiviral activities when conjugated with biopolymers. The development of such technology has potential to develop materials that are more effective in the field of health science. Considering the importance and uniqueness of this concept, the present review aims to discuss the use of biopolymer-decorated metal nanoparticles for combating various diseases caused by microbial pathogens. Moreover, the nanotoxicity aspect has also been discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Magnetic responsive of paclitaxel delivery system based on SPION and palmitoyl chitosan

    Energy Technology Data Exchange (ETDEWEB)

    Mansouri, Mona [Department of Biomedical Engineering, Amirkabir University of Technology, P.O. Box: 15875/4413, Tehran 159163/4311 (Iran, Islamic Republic of); Nazarpak, Masoumeh Haghbin, E-mail: haghbin@aut.ac.ir [New Technologies Research Center (NTRC), Amirkabir University of Technology, Tehran 15875-4413 (Iran, Islamic Republic of); Solouk, Atefeh [Department of Biomedical Engineering, Amirkabir University of Technology, P.O. Box: 15875/4413, Tehran 159163/4311 (Iran, Islamic Republic of); Akbari, Somaye [Department of Textile Engineering, Amirkabir University of Technology, P.O. Box: 15875/4413, Tehran 15916/34311 (Iran, Islamic Republic of); Hasani-Sadrabadi, Mohammad Mahdi [Parker H. Petit Institute for Bioengineering and Bioscience, G. W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0295 (United States)

    2017-01-01

    Concerns over cancer treatment have largely focused on chemotherapy and its consequent side effects. Utilizing nanocarriers is thought to be a panacea for mitigating the limitations of chemotherapy, and increasing its safety and efficacy. Magnetically driven Paclitaxel delivery systems are among the commonly investigated types of nanocarriers over the last two decades. In this context, we tried to highlight the application of an AC magnetic field and validate its consequential effects on drug delivery pattern and cell death in such nanodevices. So the aim of this study is to develop an appropriate matrix (Palmitoyl chitosan) co-encapsulated with superparamagnetic iron oxide nanoparticles (SPIONs) and anticancer drug, Paclitaxel (PTX) via the nanoprecipitation process. Synthesized nanoparticles were characterized by Dynamic Light Scattering (DLS) and their magnetic properties were investigated by Vibrating Sample Magnetometer (VSM). At initial loading of 10 wt% Paclitaxel, the maximum loading efficiency of nanoparticles with and without SPIONs was in the range of 69% and 72.3%, respectively. In addition, in vitro release data revealed that by the application of a magnetic field, release kinetic changed to the magnetic responsive pattern. Encapsulating anticancer drug in a synthesized nanosystem not only increased the amount of drug in cancer cells but also enhanced cell death (MCF-7) due to hyperthermic effects of SPIONs in the presence of an external magnetic field. In summary, these findings indicate that the resultant nanoparticles may serve as a biocompatible and biodegradable carrier for the precise delivery of powerful cytotoxic anticancer agents such as PTX. - Highlights: ●This paper focuses on using an AC magnetic field to enhance the drug entry and to increase its concentration in the cell. ●The rate of drug release is highly dependent on the amount of available pores for transporting molecules.

  16. Efficient gene delivery to human umbilical cord mesenchymal stem cells by cationized Porphyra yezoensis polysaccharide nanoparticles.

    Science.gov (United States)

    Yu, Qingtong; Cao, Jin; Chen, Baoding; Deng, Wenwen; Cao, Xia; Chen, Jingjing; Wang, Yan; Wang, Shicheng; Yu, Jiangnan; Xu, Ximing; Gao, Xiangdong

    2015-01-01

    This study centered on an innovative application of Porphyra yezoensis polysaccharide (PPS) with cationic modification as a safe and efficient nonviral gene vector to deliver a plasmid encoding human Wnt3a (pWnt3a) into human umbilical cord mesenchymal stem cells (HUMSCs). After modification with branched low-molecular-weight (1,200 Da) polyethylenimine, the cationized PPS (CPPS) was combined with pWnt3a to form spherical nanoscale particles (CPPS-pWnt3a nanoparticles). Particle size and distribution indicated that the CPPS-pWnt3a nanoparticles at a CPPS:pWnt3a weight ratio of 40:1 might be a potential candidate for DNA plasmid transfection. A cytotoxicity assay demonstrated that the nanoparticles prepared at a CPPS:pWnt3a weight ratio of 40:1 were nontoxic to HUMSCs compared to those of Lipofectamine 2000 and polyethylenimine (25 kDa). These nanoparticles were further transfected to HUMSCs. Western blotting demonstrated that the nanoparticles (CPPS:pWnt3a weight ratio 40:1) had the greatest transfection efficiency in HUMSCs, which was significantly higher than that of Lipofectamine 2000; however, when the CPPS:pWnt3a weight ratio was increased to 80:1, the nanoparticle-treated group showed no obvious improvement in translation efficiency over Lipofectamine 2000. Therefore, CPPS, a novel cationic polysaccharide derived from P. yezoensis, could be developed into a safe, efficient, nonviral gene vector in a gene-delivery system.

  17. Nanotechnology: from In Vivo Imaging System to Controlled Drug Delivery.

    Science.gov (United States)

    Mir, Maria; Ishtiaq, Saba; Rabia, Samreen; Khatoon, Maryam; Zeb, Ahmad; Khan, Gul Majid; Ur Rehman, Asim; Ud Din, Fakhar

    2017-08-17

    Science and technology have always been the vitals of human's struggle, utilized exclusively for the development of novel tools and products, ranging from micro- to nanosize. Nanotechnology has gained significant attention due to its extensive applications in biomedicine, particularly related to bio imaging and drug delivery. Various nanodevices and nanomaterials have been developed for the diagnosis and treatment of different diseases. Herein, we have described two primary aspects of the nanomedicine, i.e., in vivo imaging and drug delivery, highlighting the recent advancements and future explorations. Tremendous advancements in the nanotechnology tools for the imaging, particularly of the cancer cells, have recently been observed. Nanoparticles offer a suitable medium to carryout molecular level modifications including the site-specific imaging and targeting. Invention of radionuclides, quantum dots, magnetic nanoparticles, and carbon nanotubes and use of gold nanoparticles in biosensors have revolutionized the field of imaging, resulting in easy understanding of the pathophysiology of disease, improved ability to diagnose and enhanced therapeutic delivery. This high specificity and selectivity of the nanomedicine is important, and thus, the recent advancements in this field need to be understood for a better today and a more prosperous future.

  18. Nanotechnology: from In Vivo Imaging System to Controlled Drug Delivery

    Science.gov (United States)

    Mir, Maria; Ishtiaq, Saba; Rabia, Samreen; Khatoon, Maryam; Zeb, Ahmad; Khan, Gul Majid; ur Rehman, Asim; ud Din, Fakhar

    2017-08-01

    Science and technology have always been the vitals of human's struggle, utilized exclusively for the development of novel tools and products, ranging from micro- to nanosize. Nanotechnology has gained significant attention due to its extensive applications in biomedicine, particularly related to bio imaging and drug delivery. Various nanodevices and nanomaterials have been developed for the diagnosis and treatment of different diseases. Herein, we have described two primary aspects of the nanomedicine, i.e., in vivo imaging and drug delivery, highlighting the recent advancements and future explorations. Tremendous advancements in the nanotechnology tools for the imaging, particularly of the cancer cells, have recently been observed. Nanoparticles offer a suitable medium to carryout molecular level modifications including the site-specific imaging and targeting. Invention of radionuclides, quantum dots, magnetic nanoparticles, and carbon nanotubes and use of gold nanoparticles in biosensors have revolutionized the field of imaging, resulting in easy understanding of the pathophysiology of disease, improved ability to diagnose and enhanced therapeutic delivery. This high specificity and selectivity of the nanomedicine is important, and thus, the recent advancements in this field need to be understood for a better today and a more prosperous future.

  19. Scalable fabrication of size-controlled chitosan nanoparticles for oral delivery of insulin.

    Science.gov (United States)

    He, Zhiyu; Santos, Jose Luis; Tian, Houkuan; Huang, Huahua; Hu, Yizong; Liu, Lixin; Leong, Kam W; Chen, Yongming; Mao, Hai-Quan

    2017-06-01

    Controlled delivery of protein would find diverse therapeutic applications. Formulation of protein nanoparticles by polyelectrolyte complexation between the protein and a natural polymer such as chitosan (CS) is a popular approach. However, the current method of batch-mode mixing faces significant challenges in scaling up while maintaining size control, high uniformity, and high encapsulation efficiency. Here we report a new method, termed flash nanocomplexation (FNC), to fabricate insulin nanoparticles by infusing aqueous solutions of CS, tripolyphosphate (TPP), and insulin under rapid mixing condition (Re > 1600) in a multi-inlet vortex mixer. In comparison with the bulk-mixing method, the optimized FNC process produces CS/TPP/insulin nanoparticles with a smaller size (down to 45 nm) and narrower size distribution, higher encapsulation efficiency (up to 90%), and pH-dependent nanoparticle dissolution and insulin release. The CS/TPP/insulin nanoparticles can be lyophilized and reconstituted without loss of activity, and produced at a throughput of 5.1 g h -1 when a flow rate of 50 mL min -1 is used. Evaluated in a Type I diabetes rat model, the smaller nanoparticles (45 nm and 115 nm) control the blood glucose level through oral administration more effectively than the larger particles (240 nm). This efficient, reproducible and continuous FNC technique is amenable to scale-up in order to address the critical barrier of manufacturing for the translation of protein nanoparticles. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Supramolecular nanoparticles generated by the self-assembly of polyrotaxanes for antitumor drug delivery

    Directory of Open Access Journals (Sweden)

    Liu R

    2012-10-01

    Full Text Available Rong Liu,1,2,* Yusi Lai,1,* Bin He,1 Yuan Li,1 Gang Wang,1 Shuang Chang,1 Zhongwei Gu1 1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China; 2Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China*These authors contributed equally to this paperAbstract: A new approach of fabricating supramolecular nanoparticles generated by self-assembly polyrotaxanes for antitumor drug delivery has been reported. Cinnamic-acid-modified poly(ethylene glycol chains were threaded in a-cyclodextrins to form polyrotaxanes. The polyrotaxanes self-assembled supramolecular nanoparticles. The morphology of the nanoparticles was changed from nanovesicle to micelle after the antitumor drug, doxorubicin, was loaded. The release profile of the drug-loaded nanoparticles was investigated, and it was found that the sustaining release time could last for 32 hours. The drug-loaded nanoparticles were co-cultured with mouse 4T1 breast cancer cells with a drug concentration of 10 µg/mL; the cell survival rate was 3.3% after a 72-hour incubation. In an in vivo study of breast cancer in a mouse model, the drug-loaded nanoparticles were injected in the tail veins of mice with a dose of 5 mg/kg body weight. The tumor inhibition rate of drug-loaded nanoparticles was 53%, which was better than that of doxorubicin hydrochloride. The cardiac toxicity of doxorubicin was decreased greatly after the encapsulation into supramolecular polyrotaxane nanoparticles.Keywords: polyrotaxane, self-assembly, nanoparticle, doxorubicin, supermolecular

  1. Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement.

    Science.gov (United States)

    Li, ChunYan; Huang, ZhiGang; Liu, ZheShuo; Ci, LiQian; Liu, ZhePeng; Liu, Yu; Yan, XueYing; Lu, WeiYue

    Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN) in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S) were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050), good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA) assay of IFN demonstrated that PBNP-S could stay in the vagina and maintain intravaginal IFN level for much longer time than IFN solution (24 hours vs several hours) without obvious histological irritation to vaginal mucosa after vaginal administration to mice. In summary, good stability, easy loading and controllable release of protein therapeutics, in vitro and in vivo mucoadhesive properties and local safety of PBNP-S suggested it as a promising nanoscale mucoadhesive drug delivery

  2. Comprehensive study of the drug delivery properties of poly(l-lactide)-poly(ethylene glycol) nanoparticles in rats and tumor-bearing mice.

    Science.gov (United States)

    Shalgunov, Vladimir; Zaytseva-Zotova, Daria; Zintchenko, Arkadi; Levada, Tatiana; Shilov, Yuri; Andreyev, Dmitry; Dzhumashev, Dzhangar; Metelkin, Evgeny; Urusova, Alexandra; Demin, Oleg; McDonnell, Kevin; Troiano, Greg; Zale, Stephen; Safarovа, Elmira

    2017-09-10

    Nanoparticles made of polylactide-poly(ethylene glycol) block-copolymer (PLA-PEG) are promising vehicles for drug delivery due to their biodegradability and controllable payload release. However, published data on the drug delivery properties of PLA-PEG nanoparticles are heterogeneous in terms of nanoparticle characteristics and mostly refer to low injected doses (a few mg nanoparticles per kg body weight). We have performed a comprehensive study of the biodistribution of nanoparticle formulations based on PLA-PEG nanoparticles of ~100nm size at injected doses of 30 to 140mg/kg body weight in healthy rats and nude tumor-bearing mice. Nanoparticle formulations differed by surface PEG coverage and by release kinetics of the encapsulated model active pharmaceutical ingredient (API). Increase in PEG coverage prolonged nanoparticle circulation half-life up to ~20h in rats and ~10h in mice and decreased retention in liver, spleen and lungs. Circulation half-life of the encapsulated API grew monotonously as the release rate slowed down. Plasma and tissue pharmacokinetics was dose-linear for inactive nanoparticles, but markedly dose-dependent for the model therapeutic formulation, presumably because of the toxic effects of released API. A mathematical model of API distribution calibrated on the data for inactive nanoparticles and conventional API form correctly predicted the distribution of the model therapeutic formulation at the lowest investigated dose, but for higher doses the toxic action of the released API had to be explicitly modelled. Our results provide a coherent illustration of the ability of controllable-release PLA-PEG nanoparticles to serve as an effective drug delivery platform to alter API biodistribution. They also underscore the importance of physiological effects of released drug in determining the biodistribution of therapeutic drug formulations at doses approaching tolerability limits. Copyright © 2017 The Authors. Published by Elsevier B.V. All

  3. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers

    Directory of Open Access Journals (Sweden)

    Chih-Hung Lin

    2017-04-01

    Full Text Available Chemical and enzymatic barriers in the gastrointestinal (GI tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs.

  4. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers.

    Science.gov (United States)

    Lin, Chih-Hung; Chen, Chun-Han; Lin, Zih-Chan; Fang, Jia-You

    2017-04-01

    Chemical and enzymatic barriers in the gastrointestinal (GI) tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs) are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs. Copyright © 2017. Published by Elsevier B.V.

  5. Biodegradable Oxamide-Phenylene-Based Mesoporous Organosilica Nanoparticles with Unprecedented Drug Payloads for Delivery in Cells

    KAUST Repository

    Croissant, Jonas; Fatieiev, Yevhen; Julfakyan, Khachatur; Lu, Jie; Emwas, Abdelhamid; Anjum, Dalaver; Omar, Haneen; Tamanoi, Fuyuhiko; Zink, Jeffrey; Khashab, Niveen M.

    2016-01-01

    We describe biodegradable mesoporous hybrid NPs in the presence of proteins, and its application for drug delivery. We synthesized oxamide-phenylene-based mesoporous organosilica nanoparticles (MON) in the absence of silica source which had a

  6. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could...

  7. Engineering of polymer-surfactant nanoparticles of doxycycline hydrochloride for ocular drug delivery.

    Science.gov (United States)

    Pokharkar, Varsha; Patil, Vikram; Mandpe, Leenata

    2015-01-01

    Physiologic barriers of the eye, short precorneal drug residence time and poor corneal penetration are the few reasons for reduced ocular bioavailability. This study was aimed to develop novel polymer-surfactant nanoparticles of hydrophilic drug doxycycline hydrochloride (DXY) to improve precorneal residence time and drug penetration. Nanoparticles were formulated using emulsion cross-linking method and the formulation was optimized using factorial design. The prepared formulation was characterized for particle size, ζ potential, encapsulation efficiency, in vitro drug release and ex vivo drug diffusion studies. The antibacterial activity studies were also carried out against Escherichia coli and Staphylococcus aureus using the cup-plate method. In vivo eye irritation study was carried out by a modified Draize test in rabbits. The particle size was found to be in the range of 331-850 nm. About 45-80% of the drug was found to be encapsulated in the nanoparticles. In vitro release demonstrated sustained release profile. Lower flux values in case of nanoparticles as compared to DXY pure drug solution in ex vivo diffusion studies confirmed the sustained release. The nanoparticles were found to be significantly effective (p nanoparticles in both the E. coli and S. aureus strains. The formulation was found to be stable over entire stability period. The developed formulation is safe and suitable for sustained ocular drug delivery.

  8. Smart Magnetically Responsive Hydrogel Nanoparticles Prepared by a Novel Aerosol-Assisted Method for Biomedical and Drug Delivery Applications

    Directory of Open Access Journals (Sweden)

    Ibrahim M. El-Sherbiny

    2011-01-01

    Full Text Available We have developed a novel spray gelation-based method to synthesize a new series of magnetically responsive hydrogel nanoparticles for biomedical and drug delivery applications. The method is based on the production of hydrogel nanoparticles from sprayed polymeric microdroplets obtained by an air-jet nebulization process that is immediately followed by gelation in a crosslinking fluid. Oligoguluronate (G-blocks was prepared through the partial acid hydrolysis of sodium alginate. PEG-grafted chitosan was also synthesized and characterized (FTIR, EA, and DSC. Then, magnetically responsive hydrogel nanoparticles based on alginate and alginate/G-blocks were synthesized via aerosolization followed by either ionotropic gelation or both ionotropic and polyelectrolyte complexation using CaCl2 or PEG-g-chitosan/CaCl2 as crosslinking agents, respectively. Particle size and dynamic swelling were determined using dynamic light scattering (DLS and microscopy. Surface morphology of the nanoparticles was examined using SEM. The distribution of magnetic cores within the hydrogels nanoparticles was also examined using TEM. In addition, the iron and calcium contents of the particles were estimated using EDS. Spherical magnetic hydrogel nanoparticles with average particle size of 811 ± 162 to 941 ± 2 nm were obtained. This study showed that the developed method is promising for the manufacture of hydrogel nanoparticles, and it represents a relatively simple and potential low-cost system.

  9. Optical methods for creating delivery systems of chemical compounds to plant roots

    Science.gov (United States)

    Kuznetsov, Pavel E.; Rogacheva, Svetlana M.; Arefeva, Oksana A.; Minin, Dmitryi V.; Tolmachev, Sergey A.; Kupadze, Machammad S.

    2004-08-01

    Spectrophotometric and fluorescence methods have been used for creation and investigation of various systems of target delivery of chemical compounds to roots of plants. The possibility of using liposomes, incrusted by polysaccharides of the external surface of nitrogen-fixing rizospheric bacteria Azospirillum brasilense SP 245, and nanoparticles incrusted by polysaccharides of wheat roots, as the named systems has been shown. The important role of polysaccharide-polysaccharide interaction in the adsorption processes of bacteria on wheat roots has been demonstrated.

  10. Novel targeted siRNA-loaded hybrid nanoparticles: preparation, characterization and in vitro evaluation.

    Science.gov (United States)

    Dim, Nneka; Perepelyuk, Maryna; Gomes, Olukayode; Thangavel, Chellappagounder; Liu, Yi; Den, Robert; Lakshmikuttyamma, Ashakumary; Shoyele, Sunday A

    2015-09-26

    siRNAs have a high potential for silencing critical molecular pathways that are pathogenic. Nevertheless, their clinical application has been limited by a lack of effective and safe nanotechnology-based delivery system that allows a controlled and safe transfection to cytosol of targeted cells without the associated adverse effects. Our group recently reported a very effective and safe hybrid nanoparticle delivery system composing human IgG and poloxamer-188 for siRNA delivery to cancer cells. However, these nanoparticles need to be optimized in terms of particle size, loading capacity and encapsulation efficiency. In the present study, we explored the effects of certain production parameters on particle size, loading capacity and encapsulation efficiency. Further, to make these nanoparticles more specific in their delivery of siRNA, we conjugated anti-NTSR1-mAb to the surface of these nanoparticles to target NTSR1-overexpressing cancer cells. The mechanism of siRNA release from these antiNTSR1-mAb functionalized nanoparticles was also elucidated. It was demonstrated that the concentration of human IgG in the starting nanoprecipitation medium and the rotation speed of the magnetic stirrer influenced the encapsulation efficiency, loading capacity and the size of the nanoparticles produced. We also successfully transformed these nanoparticles into actively targeted nanoparticles by functionalizing with anti-NTSR1-mAb to specifically target NTSR1-overexpressing cancer cells, hence able to avoid undesired accumulation in normal cells. The mechanism of siRNA release from these nanoparticles was elucidated to be by Fickian diffusion. Using flow cytometry and fluorescence microscopy, we were able to confirm the active involvement of NTSR1 in the uptake of these anti-NTSR1-mAb functionalized hybrid nanoparticles by lung adenocarcinoma cells. This hybrid nanoparticle delivery system can be used as a platform technology for intracellular delivery of siRNAs to NTSR1

  11. Cytosolic and Nuclear Delivery of CRISPR/Cas9-ribonucleoprotein for Gene Editing Using Arginine Functionalized Gold Nanoparticles.

    Science.gov (United States)

    Mout, Rubul; Rotello, Vincent M

    2017-10-20

    In this protocol, engineered Cas9-ribonucleoprotein (Cas9 protein and sgRNA, together called Cas9-RNP) and gold nanoparticles are used to make nanoassemblies that are employed to deliver Cas9-RNP into cell cytoplasm and nucleus. Cas9 protein is engineered with an N-terminus glutamic acid tag (E-tag or En, where n = the number of glutamic acid in an E-tag and usually n = 15 or 20), C-terminus nuclear localizing signal (NLS), and a C-terminus 6xHis-tag. [Cas9En hereafter] To use this protocol, the first step is to generate the required materials (gold nanoparticles, recombinant Cas9En, and sgRNA). Laboratory-synthesis of gold nanoparticles can take up to a few weeks, but can be synthesized in large batches that can be used for many years without compromising the quality. Cas9En can be cloned from a regular SpCas9 gene (Addgene plasmid id = 47327), and expressed and purified using standard laboratory procedures which are not a part of this protocol. Similarly, sgRNA can be laboratory-synthesized using in vitro transcription from a template gene (Addgene plasmid id = 51765) or can be purchased from various sources. Once these materials are ready, it takes about ~30 min to make the Cas9En-RNP complex and 10 min to make the Cas9En-RNP/nanoparticles nanoassemblies, which are immediately used for delivery (Figure 1). Complete delivery (90-95% cytoplasmic and nuclear delivery) is achieved in less than 3 h. Follow-up editing experiments require additional time based on users' need. Synthesis of arginine functionalized gold nanoparticles (ArgNPs) (Yang et al ., 2011), expression of recombinant Cas9En, and in vitro synthesis of sgRNA is reported elsewhere (Mout et al ., 2017). We report here only the generation of the delivery vehicle i.e. , the fabrication of Cas9En-RNP/ArgNPs nanoassembly.

  12. Self-aggregated nanoparticles based on amphiphilic poly(lactic acid-grafted-chitosan copolymer for ocular delivery of amphotericin B

    Directory of Open Access Journals (Sweden)

    Zhou WJ

    2013-09-01

    activity similar to that of free amphotericin B against Candida albicans. The in vivo ocular pharmacokinetic study suggested that the PLA-g-CS nanoparticles have the advantage of prolonging residence time at the ocular surface. The corneal penetration study showed that the PLA-g-CS nanoparticles could penetrate into the cornea. Conclusion: Our results suggest that this nanoparticulate vehicle based on a PLA-g-CS copolymer might be a promising system for effective ocular delivery of amphotericin B. Keywords: chitosan, poly(lactic acid, nanoparticles, amphotericin B 

  13. In vivo evaluation of a conjugated poly(lactide-ethylene glycol nanoparticle depot formulation for prolonged insulin delivery in the diabetic rabbit model

    Directory of Open Access Journals (Sweden)

    Tomar L

    2013-02-01

    Full Text Available Lomas Tomar,1,2 Charu Tyagi,1,3 Manoj Kumar,2 Pradeep Kumar,1 Harpal Singh,2 Yahya E Choonara,1 Viness Pillay11University of the Witwatersrand, Faculty of Health Sciences, Department of Pharmacy and Pharmacology, Johannesburg, Gauteng, South Africa; 2Centre for Biomedical Engineering, Indian Institute of Technology, Delhi, India; 3VSPG College, Chaudhary Charan Singh University, Meerut, IndiaAbstract: Poly(ethylene glycol (PEG and polylactic acid (PLA-based copolymeric nanoparticles were synthesized and investigated as a carrier for prolonged delivery of insulin via the parenteral route. Insulin loading was simultaneously achieved with particle synthesis using a double emulsion solvent evaporation technique, and the effect of varied PEG chain lengths on particle size and insulin loading efficiency was determined. The synthesized copolymer and nanoparticles were analyzed by standard polymer characterization techniques of gel permeation chromatography, dynamic light scattering, nuclear magnetic resonance, and transmission electron microscopy. In vitro insulin release studies performed under simulated conditions provided a near zero-order release pattern up to 10 days. In vivo animal studies were undertaken with varied insulin loads of nanoparticles administered subcutaneously to fed diabetic rabbits and, of all doses administered, nanoparticles containing 50 IU of insulin load per kg body weight controlled the blood glucose level within the physiologically normal range of 90–140 mg/dL, and had a prolonged effect for more than 7 days. Histopathological evaluation of tissue samples from the site of injection showed no signs of inflammation or aggregation, and established the nontoxic nature of the prepared copolymeric nanoparticles. Further, the reaction profiles for PLA-COOH and NH2-PEGDA-NH2 were elucidated using molecular mechanics energy relationships in vacuum and in a solvated system by exploring the spatial disposition of various

  14. Preparation and Characterization of Cationic PLA-PEG Nanoparticles for Delivery of Plasmid DNA

    Directory of Open Access Journals (Sweden)

    Zou Weiwei

    2009-01-01

    Full Text Available Abstract The purpose of the present work was to formulate and evaluate cationic poly(lactic acid-poly(ethylene glycol (PLA-PEG nanoparticles as novel non-viral gene delivery nano-device. Cationic PLA-PEG nanoparticles were prepared by nanoprecipitation method. The gene loaded nanoparticles were obtained by incubating the report gene pEGFP with cationic PLA-PEG nanoparticles. The physicochemical properties (e.g., morphology, particle size, surface charge, DNA binding efficiency and biological properties (e.g., integrity of the released DNA, protection from nuclease degradation, plasma stability, in vitro cytotoxicity, and in vitro transfection ability in Hela cells of the gene loaded PLA-PEG nanoparticles were evaluated, respectively. The obtained cationic PLA-PEG nanoparticles and gene loaded nanoparticles were both spherical in shape with average particle size of 89.7 and 128.9 nm, polydispersity index of 0.185 and 0.161, zeta potentials of +28.9 and +16.8 mV, respectively. The obtained cationic PLA-PEG nanoparticles with high binding efficiency (>95% could protect the loaded DNA from the degradation by nuclease and plasma. The nanoparticles displayed sustained-release properties in vitro and the released DNA maintained its structural and functional integrity. It also showed lower cytotoxicity than Lipofectamine 2000 and could successfully transfect gene into Hela cells even in presence of serum. It could be concluded that the established gene loaded cationic PLA-PEG nanoparticles with excellent properties were promising non-viral nano-device, which had potential to make cancer gene therapy achievable.

  15. Electrospun Composites of Polycaprolactone and Porous Silicon Nanoparticles for the Tunable Delivery of Small Therapeutic Molecules

    Directory of Open Access Journals (Sweden)

    Steven J. P. McInnes

    2018-03-01

    Full Text Available This report describes the use of an electrospun composite of poly(ε-caprolactone (PCL fibers and porous silicon (pSi nanoparticles (NPs as an effective system for the tunable delivery of camptothecin (CPT, a small therapeutic molecule. Both materials are biodegradable, abundant, low-cost, and most importantly, have no known cytotoxic effects. The composites were treated with and without sodium hydroxide (NaOH to investigate the wettability of the porous network for drug release and cell viability measurements. CPT release and subsequent cell viability was also investigated. We observed that the cell death rate was not only affected by the addition of our CPT carrier, pSi, but also by increasing the rate of dissolution via treatment with NaOH. This is the first example of loading pSi NPs as a therapeutics nanocarrier into electronspun PCL fibers and this system opens up new possibilities for the delivery of molecular therapeutics.

  16. Lipid-Based Liquid Crystalline Nanoparticles Facilitate Cytosolic Delivery of siRNA via Structural Transformation.

    Science.gov (United States)

    He, Shufang; Fan, Weiwei; Wu, Na; Zhu, Jingjing; Miao, Yunqiu; Miao, Xiaran; Li, Feifei; Zhang, Xinxin; Gan, Yong

    2018-04-11

    RNA interference (RNAi) technology has shown great promise for the treatment of cancer and other genetic disorders. Despite the efforts to increase the target tissue distribution, the safe and effective delivery of siRNA to the diseased cells with sufficient cytosolic transport is another critical factor for successful RNAi clinical application. Here, the constructed lipid-based liquid crystalline nanoparticles, called nano-Transformers, can transform thestructure in the intracellular acidic environment and perform high-efficient siRNA delivery for cancer treatment. The developed nano-Transformers have satisfactory siRNA loading efficiency and low cytotoxicity. Different from the traditional cationic nanocarriers, the endosomal membrane fusion induced by the conformational transition of lipids contributes to the easy dissociation of siRNA from nanocarriers and direct release of free siRNA into cytoplasm. We show that transfection with cyclin-dependent kinase 1 (CDK1)-siRNA-loaded nano-Transformers causes up to 95% reduction of relevant mRNA in vitro and greatly inhibits the tumor growth without causing any immunogenic response in vivo. This work highlights that the lipid-based nano-Transformers may become the next generation of siRNA delivery system with higher efficacy and improved safety profiles.

  17. Cytotoxic effects of gold nanoparticles exposure employing in vitro animal cell culture system as part of nanobiosafety

    Science.gov (United States)

    Ambwani, Sonu; Kakade Datta, P.; Kandpal, Deepika; Arora, Sandeep; Ambwani, Tanuj Kumar

    2016-04-01

    Metal Nanoparticles are exploited in different fields that include biomedical sector where they are utilized in drug and gene delivery, biosensors, cancer treatment and diagnostic tools. Despite of their benefits, there has been serious concerns about possible side effects of several nanoparticles. Gold nanoparticles (AuNPs) are exploited for bio-imaging, biosensing, drug delivery, transfection and diagnosis. These nanoparticles may get released into the environment in high amounts at all stages of production, recycling and disposal. Since the manufacture and use of nanoparticles are increasing, humans/ animals are more likely to be exposed occupationally or via consumer products and the environment. The emergence of the new field of nanotoxicity has spurred great interest in a wide variety of materials and their possible effects on living systems. Animal cell culture system is considered as a sensitive indicator against exposure of such materials. Keeping in view the above scenario, present study was carried out to evaluate effect of AuNPs exposure in primary and cell line culture system employing chicken embryo fibroblast (CEF) culture and HeLa cell line culture through MTT assay. Minimum cytotoxic dose was found to be 60 µg/ml and 50 µg/ml in CEF and HeLa cells, respectively. Thus, it could be inferred that even a very low concentration of AuNPs could lead to cytotoxic effects in cell culture based studies.

  18. Cellular membrane trafficking of mesoporous silica nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Fang, I-Ju [Iowa State Univ., Ames, IA (United States)

    2012-01-01

    This dissertation mainly focuses on the investigation of the cellular membrane trafficking of mesoporous silica nanoparticles. We are interested in the study of endocytosis and exocytosis behaviors of mesoporous silica nanoparticles with desired surface functionality. The relationship between mesoporous silica nanoparticles and membrane trafficking of cells, either cancerous cells or normal cells was examined. Since mesoporous silica nanoparticles were applied in many drug delivery cases, the endocytotic efficiency of mesoporous silica nanoparticles needs to be investigated in more details in order to design the cellular drug delivery system in the controlled way. It is well known that cells can engulf some molecules outside of the cells through a receptor-ligand associated endocytosis. We are interested to determine if those biomolecules binding to cell surface receptors can be utilized on mesoporous silica nanoparticle materials to improve the uptake efficiency or govern the mechanism of endocytosis of mesoporous silica nanoparticles. Arginine-glycine-aspartate (RGD) is a small peptide recognized by cell integrin receptors and it was reported that avidin internalization was highly promoted by tumor lectin. Both RGD and avidin were linked to the surface of mesoporous silica nanoparticle materials to investigate the effect of receptor-associated biomolecule on cellular endocytosis efficiency. The effect of ligand types, ligand conformation and ligand density were discussed in Chapter 2 and 3. Furthermore, the exocytosis of mesoporous silica nanoparticles is very attractive for biological applications. The cellular protein sequestration study of mesoporous silica nanoparticles was examined for further information of the intracellular pathway of endocytosed mesoporous silica nanoparticle materials. The surface functionality of mesoporous silica nanoparticle materials demonstrated selectivity among the materials and cancer and normal cell lines. We aimed to determine

  19. PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery.

    Science.gov (United States)

    Chan, Juliana M; Zhang, Liangfang; Yuet, Kai P; Liao, Grace; Rhee, June-Wha; Langer, Robert; Farokhzad, Omid C

    2009-03-01

    Current approaches to encapsulate and deliver therapeutic compounds have focused on developing liposomal and biodegradable polymeric nanoparticles (NPs), resulting in clinically approved therapeutics such as Doxil/Caelyx and Genexol-PM, respectively. Our group recently reported the development of biodegradable core-shell NP systems that combined the beneficial properties of liposomal and polymeric NPs for controlled drug delivery. Herein we report the parameters that alter the biological and physicochemical characteristics, stability, drug release properties and cytotoxicity of these core-shell NPs. We further define scalable processes for the formulation of these NPs in a reproducible manner. These core-shell NPs consist of (i) a poly(D,L-lactide-co-glycolide) hydrophobic core, (ii) a soybean lecithin monolayer, and (iii) a poly(ethylene glycol) shell, and were synthesized by a modified nanoprecipitation method combined with self-assembly. Preparation of the NPs showed that various formulation parameters such as the lipid/polymer mass ratio and lipid/lipid-PEG molar ratio controlled NP physical stability and size. We encapsulated a model chemotherapy drug, docetaxel, in the NPs and showed that the amount of lipid coverage affected its drug release kinetics. Next, we demonstrated a potentially scalable process for the formulation, purification, and storage of NPs. Finally, we tested the cytotoxicity using MTT assays on two model human cell lines, HeLa and HepG2, and demonstrated the biocompatibility of these particles in vitro. Our data suggest that the PLGA-lecithin-PEG core-shell NPs may be a useful new controlled release drug delivery system.

  20. Targeted delivery using peptide-functionalised gold nanoparticles to white adipose tissues of obese rats

    Energy Technology Data Exchange (ETDEWEB)

    Thovhogi, Ntevheleni; Sibuyi, Nicole [Medical Research Council, Diabetes Research Group (South Africa); Meyer, Mervin [University of the Western Cape, Biotechnology Department, DST/Mintek Nanotechnology Innovation Centre (South Africa); Onani, Martin [University of the Western Cape, Chemistry Department (South Africa); Madiehe, Abram, E-mail: amadiehe@csir.co.za [Medical Research Council, Diabetes Research Group (South Africa)

    2015-02-15

    Obesity is a complex metabolic disease of excessive fat accumulation. It is a worldwide epidemic affecting billions of people. Current pharmacological treatment of obesity remains limited and ineffective due to systemic drug toxicity and undesirable side effects. The current epidemic raises a serious need for development of safer drugs to treat obesity. Nanotechnology-based drug delivery system for administering pharmaceutical compound to achieve therapeutic effects is currently an exciting field in cancer treatment. Drug delivery involves either modification of drug release profile, absorption, distribution and/or elimination, for the benefit of improving drug efficacy and safety. Therefore, nanotechnology holds promise in the treatment of diseases including obesity. Gold nanoparticles (GNPs) functionalised with different biomolecules have been successfully used as drug delivery, labelling and imaging tools in biomedical research. In this study, the binding-specificity and targeting ability of adipose homing peptide (AHP)-functionalised GNPs (AHP-GNPs) were evaluated using flow cytometry and inductively coupled plasma-optical emission spectroscopy. Caco-2 cells and rats fed either chow or a high-fat diet were treated with either unfunctionalised GNPs or AHP-GNPs. Cellular uptake of GNPs was detected in cells treated with AHP-GNPs and not those treated with GNPs alone. Binding of AHP to cells was both temperature- and concentration-dependent. Compared to rats treated with GNPs alone, treatment of obese rats with AHP-GNPs resulted in the targeted delivery of the GNPs to the white adipose tissue (WAT). This paper reports the successful targeting of AHP-functionalised GNPs to WAT of obese rats.