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Sample records for polymeric drug delivery

  1. Bioadhesive polymeric platforms for transmucosal drug delivery ...

    African Journals Online (AJOL)

    Bioadhesive polymeric platforms for transmucosal drug delivery systems – a review. ... administration of certain classes of drugs, especially peptides and proteins. ... characteristics of desired bioadhesive polymers, this article then proceeds to ...

  2. Electrospun polymeric nanofibers for transdermal drug delivery

    Directory of Open Access Journals (Sweden)

    Mahya Rahmani

    2017-04-01

    Full Text Available Conventional transdermal drug delivery systems (TDDS have been designed for drug delivery through the skin. These systems use the permeability property of stratum corneum, the outermost surface layer of the skin. Applying polymeric micro and nanofibers in drug delivery has recently attracted great attention and the electrospinning technique is the preferred method for polymeric micro-nanofibers fabrication with a great potential for drug delivery. More studies in the field of nanofibers containing drug are divided two categories: first, preparation and characterization of nanofibers containing drug and second, investigation of their therapeutic applications. Drugs used in electrospun nanofibers can be categorized into three main groups, including antibiotics and antimicrobial agents, anti-inflammatory agents and vitamins with therapeutic applications. In this paper, we review the application of electrospun polymeric scaffolds in TDDS and also introduce several pharmaceutical and therapeutic agents which have been used in polymer nanofibrous patches.

  3. Biodegradable polymeric nanocarriers for pulmonary drug delivery.

    Science.gov (United States)

    Rytting, Erik; Nguyen, Juliane; Wang, Xiaoying; Kissel, Thomas

    2008-06-01

    Pulmonary drug delivery is attractive for both local and systemic drug delivery as a non-invasive route that provides a large surface area, thin epithelial barrier, high blood flow and the avoidance of first-pass metabolism. Nanoparticles can be designed to have several advantages for controlled and targeted drug delivery, including controlled deposition, sustained release, reduced dosing frequency, as well as an appropriate size for avoiding alveolar macrophage clearance or promoting transepithelial transport. This review focuses on the development and application of biodegradable polymers to nanocarrier-based strategies for the delivery of drugs, peptides, proteins, genes, siRNA and vaccines by the pulmonary route. The selection of natural or synthetic materials is important in designing particles or nanoparticle clusters with the desired characteristics, such as biocompatibility, size, charge, drug release and polymer degradation rate.

  4. BUCCAL DRUG DELIVERY USING ADHESIVE POLYMERIC PATCHES

    OpenAIRE

    R. Venkatalakshmi

    2012-01-01

    The buccal mucosa has been investigated for local drug therapy and the systemic delivery of therapeutic peptides and other drugs that are subjected to first-pass metabolism or are unstable within the rest of the gastrointestinal tract. The mucosa of the oral cavity presents a formidable barrier to drug penetration, and one method of optimizing drug delivery is by the use of adhesive dosage forms and the mucosa has a rich blood supply and it is relatively permeable. The buccal mucosa is very s...

  5. Applications of polymeric nanocapsules in field of drug delivery systems.

    Science.gov (United States)

    Rong, Xinyu; Xie, Yinghua; Hao, Xiaomei; Chen, Tao; Wang, Yingming; Liu, Yuanyuan

    2011-09-01

    Drug-loaded polymeric nanocapsules have exhibited potential applications in the field of drug delivery systems in recent years. This article entails the biodegradable polymers generally used for preparing nanocapsules, which include both natural polymers and synthetic polymers. Furthermore, the article presents a general review of the different preparation methods: nanoprecipitation method, emulsion-diffusion method, double emulsification method, emulsion-coacervation method, layer-by-layer assembly method. In addition, the analysis methods of nanocapsule characteristics, such as mean size, morphology, surface characteristics, shell thickness, encapsulation efficiency, active substance release, dispersion stability, are mentioned. Also, the applications of nanocapsules as carriers for use in drug delivery systems are reviewed, which primarily involve targeting drug delivery, controlled/sustained release drug delivery systems, transdermal drug delivery systems and improving stability and bioavailability of drugs. Nanocapsules, prepared with different biodegradable polymers, have received more and more attention and have been regarded as one of the most promising drug delivery systems.

  6. Hyaluronan polymeric micelles for topical drug delivery

    Czech Academy of Sciences Publication Activity Database

    Šmejkalová, D.; Muthný, T.; Nešporová, K.; Hermannová, M.; Achbergerová, E.; Huerta-Angelesa, G.; Marek Svoboda, M.; Čepa, M.; Machalová, V.; Luptáková, Dominika; Velebný, V.

    2017-01-01

    Roč. 156, JAN 20 (2017), s. 86-96 ISSN 0144-8617 Institutional support: RVO:61388971 Keywords : Skin penetration * Polymeric micelle * Hyaluronan Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 4.811, year: 2016

  7. Emerging Technologies of Polymeric Nanoparticles in Cancer Drug Delivery

    Directory of Open Access Journals (Sweden)

    Erik Brewer

    2011-01-01

    Full Text Available Polymeric nanomaterials have the potential to improve upon present chemotherapy delivery methods. They successfully reduce side effects while increasing dosage, increase residence time in the body, offer a sustained and tunable release, and have the ability to deliver multiple drugs in one carrier. However, traditional nanomaterial formulations have not produced highly therapeutic formulations to date due to their passive delivery methods and lack of rapid drug release at their intended site. In this paper, we have focused on a few “smart” technologies that further enhance the benefits of typical nanomaterials. Temperature and pH-responsive drug delivery devices were reviewed as methods for triggering release of encapsulating drugs, while aptamer and ligand conjugation were discussed as methods for targeted and intracellular delivery, with emphases on in vitro and in vivo works for each method.

  8. Emerging Technologies of Polymeric Nanoparticles in Cancer Drug Delivery

    International Nuclear Information System (INIS)

    Brewer, E.; Coleman, J.; Lowman, A.

    2011-01-01

    Polymeric nanomaterials have the potential to improve upon present chemotherapy delivery methods. They successfully reduce side effects while increasing dosage, increase residence time in the body, offer a sustained and tunable release, and have the ability to deliver multiple drugs in one carrier. However, traditional nanomaterial formulations have not produced highly therapeutic formulations to date due to their passive delivery methods and lack of rapid drug release at their intended site. In this paper, we have focused on a few smart technologies that further enhance the benefits of typical nanomaterials. Temperature and pH-responsive drug delivery devices were reviewed as methods for triggering release of encapsulating drugs, while aptamer and ligand conjugation were discussed as methods for targeted and intracellular delivery, with emphases on in vitro and in vivo works for each method.

  9. Polymeric Micro- and Nanofabricatced Devices for Oral Drug Delivery

    Science.gov (United States)

    Fox, Cade Brylee

    While oral drug administration is by far the most preferred route, it is accompanied by many barriers that limit drug uptake such as the low pH of the stomach, metabolic and proteolytic enzymes, and limited permeability of the intestinal epithelium. As a result, many drugs ranging from small molecules to biological therapeutics have limited oral bioavailability, precluding them from oral administration. To address this issue, microfabrication has been applied to create planar, asymmetric devices capable of binding to the lining of the gastrointestinal tract and releasing drug at high concentrations, thereby increasing oral drug uptake. While the efficacy of these devices has been validated in vitro and in vivo, modifying their surfaces with nanoscale features has potential to refine their properties for enhanced drug delivery. This dissertation first presents an approach to fabricate polymeric microdevices coated with nanowires in a rapid, high throughput manner. The nanowires demonstrate rapid drug localization onto the surface of these devices via capillary action and increased adhesion to epithelial tissue, suggesting that this fabrication technique can be used to create devices with enhanced properties for oral drug delivery. Also presented are microdevices sealed with nanostraw membranes. The nanostraw membranes provide sustained drug release by limiting drug efflux from the devices, prevent drug degradation by limiting influx of outside biomolecules, and enhance device bioadhesion by penetrating into the mucus layer of the intestinal lining. Finally, an approach that dramatically increases the capacity and efficiency of drug loading into microdevices over previous methods is presented. A picoliter-volume printer is used to print drug directly into device reservoirs in an automated fashion. The technologies presented here expand the capabilities of microdevices for oral drug delivery by incorporating nanoscale structures that enhance device bioadhesion

  10. Dissolving polymeric microneedle arrays for electrically assisted transdermal drug delivery.

    Science.gov (United States)

    Garland, Martin J; Caffarel-Salvador, Ester; Migalska, Katarzyna; Woolfson, A David; Donnelly, Ryan F

    2012-04-10

    It has recently been proposed that the combination of skin barrier impairment using microneedles (MNs) coupled with iontophoresis (ITP) may broaden the range of drugs suitable for transdermal delivery, as well as enabling the rate of delivery to be achieved with precise electronic control. However, no reports exist on the combination of ITP with in situ drug loaded polymeric MN delivery systems. Furthermore, although a number of studies have highlighted the importance of MN design for transdermal drug delivery enhancement, to date, there has been no systematic investigation of the influence of MN geometry on the performance of polymeric MN arrays which are designed to remain in contact with the skin during the period of drug delivery. As such, for the first time, this study reports on the effect of MN heigth and MN density upon the transdermal delivery of small hydrophilic compounds (theophylline, methylene blue, and fluorescein sodium) across neonatal porcine skin in vitro, with the optimised MN array design evaluated for its potential in the electrically faciliatated delivery of peptide (bovine insulin) and protein (fluorescein isothiocyanate-labelled bovine serum albumin (FTIC-BSA)) macromolecules. The results of the in vitro drug release investigations revealed that the extent of transdermal delivery was dependent upon the design of the MN array employed, whereby an increase in MN height and an increase in MN density led to an increase in the extent of transdermal drug delivery achieved 6h after MN application. Overall, the in vitro permeation studies revealed that the MN design containing 361 MNs/cm(2) of 600 μm height resulted in the greatest extent of transdermal drug delivery. As such, this design was evaluated for its potential in the MN mediated iontophoretic transdermal delivery. Whilst the combination of MN and ITP did not further enhance the extent of small molecular weight solute delivery, the extent of peptide/protein release was significantly

  11. Application of in situ polymerization for design and development of oral drug delivery systems.

    Science.gov (United States)

    Ngwuluka, Ndidi

    2010-12-01

    Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides to overcome the challenges of oral route of administration.

  12. Application of In Situ Polymerization for Design and Development of Oral Drug Delivery Systems

    OpenAIRE

    Ngwuluka, Ndidi

    2010-01-01

    Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides to overcome the challenges of oral route of administration.

  13. 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.

  14. Facilitation of transscleral drug delivery by drug loaded magnetic polymeric particles.

    Science.gov (United States)

    Mousavikhamene, Zeynab; Abdekhodaie, Mohammad J; Ahmadieh, Hamid

    2017-10-01

    A unique method was used to facilitate ocular drug delivery from periocular route by drug loaded magnetic sensitive particles. Injection of particles in periocular space along the eye axis followed by application of magnetic field in front of the eye would trigger the magnetic polymeric particles to move along the direction of magnetic force and reside against the outer surface of the sclera. This technique prevents removal of drug in the periocular space, observed in conventional transscleral drug delivery systems and hence higher amount of drug can enter the eye in a longer period of time. The experiments were performed by fresh human sclera and an experimental setup. Experimental setup was designed by side by side diffusion cell and hydrodynamic and thermal simulation of the posterior segment of the eye were applied. Magnetic polymeric particles were synthesized by alginate as a model polymer, iron oxide nanoparticles as a magnetic agent and diclofenac sodium as a model drug and characterized by SEM, TEM, DLS and FT-IR techniques. According to the SEM images, the size range of particles is around 60 to 800nm. The results revealed that the cumulative drug transfer from magnetic sensitive particles across the sclera improves by 70% in the presence of magnetic field. The results of this research show promising method of drug delivery to use magnetic properties to facilitate drug delivery to the back of the eye. Copyright © 2017. Published by Elsevier B.V.

  15. Polymeric Nanomedicine for Cancer MR Imaging and Drug Delivery

    OpenAIRE

    Khemtong, Chalermchai; Kessinger, Chase W.; Gao, Jinming

    2009-01-01

    Multifunctional nanomedicine is emerging as a highly integrated platform that allows for molecular diagnosis, targeted drug delivery, and simultaneous monitoring and treatment of cancer. Advances in polymer and materials science are critical for the successful development of these multi-component nanocomposites in one particulate system with such a small size confinement (

  16. Electrospinning of polymeric nanofibers for drug delivery applications.

    Science.gov (United States)

    Hu, Xiuli; Liu, Shi; Zhou, Guangyuan; Huang, Yubin; Xie, Zhigang; Jing, Xiabin

    2014-07-10

    Electrospinning has been recognized as a simple and versatile method for fabrication of polymer nanofibers. Various polymers that include synthetic, natural, and hybrid materials have been successfully electrospun into ultrafine fibers. The inherently high surface to volume ratio of electrospun fibers can enhance cell attachment, drug loading, and mass transfer properties. Drugs ranging from antibiotics and anticancer agents to proteins, DNA, RNA, living cells, and various growth factors have been incorporated into electrospun fibers. This article presents an overview of electrospinning techniques and their application in drug delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Polymeric Micelles, a Promising Drug Delivery System to Enhance Bioavailability of Poorly Water-Soluble Drugs

    Directory of Open Access Journals (Sweden)

    Wei Xu

    2013-01-01

    Full Text Available Oral administration is the most commonly used and readily accepted form of drug delivery; however, it is find that many drugs are difficult to attain enough bioavailability when administered via this route. Polymeric micelles (PMs can overcome some limitations of the oral delivery acting as carriers able to enhance drug absorption, by providing (1 protection of the loaded drug from the harsh environment of the GI tract, (2 release of the drug in a controlled manner at target sites, (3 prolongation of the residence time in the gut by mucoadhesion, and (4 inhibition of efflux pumps to improve the drug accumulation. To explain the mechanisms for enhancement of oral bioavailability, we discussed the special stability of PMs, the controlled release properties of pH-sensitive PMs, the prolongation of residence time with mucoadhesive PMs, and the P-gp inhibitors commonly used in PMs, respectively. The primary purpose of this paper is to illustrate the potential of PMs for delivery of poorly water-soluble drugs with bioavailability being well maintained.

  18. Polymeric Nanomaterials as Nanomembrane Entities for Biomolecule and Drug Delivery.

    Science.gov (United States)

    Albisa, Airama; Espanol, Laura; Prieto, Martin; Sebastian, Victor

    2017-01-01

    Bio-nanomaterials assembled into nanomembrane entities are actively studied to circumvent the uncontrollable list of shortcomings of conventional delivery systems: low water solubility, unfavorable stability, short circulation time in plasma, rapid clearance from the human body, poor bioavailability, non-specific toxicity against normal tissue and cells, low cellular uptake and susceptibility to enzyme degradation. Basically, these nanoentities enable to exploit the therapeutic value of many promising biomolecules and drugs (B&D), controlling the mass transport of B&D at a certain rate or even on demand if a stimulus is applied. The large surface-to-volume ratio of bio-nanomaterials as well as their tunable properties enable to increase the biocompatibility, bioavailability, solubility and permeability of many unique B&D which are otherwise difficult to deliver. This review paper will focus on the last advances of bio-nanomaterials applied as nanomembranes in biomolecule and drug delivery, as well as their more remarkable properties and applications in biomedicine. New advances have been drastically established in the production of smart nanomembranes that alter their own structure and function in response to the environment. These new insights have been used for the production of smart drug delivery nanomembranes. These nanomembranes entities have the potential to revolutionize the biomedicine but there are still some shortcomings to address in order to translate the laboratory production to the clinic. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Polymeric nanomedicine for cancer MR imaging and drug delivery.

    Science.gov (United States)

    Khemtong, Chalermchai; Kessinger, Chase W; Gao, Jinming

    2009-06-28

    Multifunctional nanomedicine is emerging as a highly integrated platform that allows for molecular diagnosis, targeted drug delivery, and simultaneous monitoring and treatment of cancer. Advances in polymer and materials science are critical for the successful development of these multi-component nanocomposites in one particulate system with such a small size confinement (nanoscopic therapeutic and diagnostic systems have been translated into clinical practice. In this feature article, we will provide an up-to-date review on the development and biomedical applications of nanocomposite materials for cancer diagnosis and therapy. An overview of each functional component, i.e. polymer carriers, MR imaging agents, and therapeutic drugs, will be presented. Integration of different functional components will be illustrated in several highlighted examples to demonstrate the synergy of the multifunctional nanomedicine design.

  20. Biocompatible Polymeric Materials Intended for Drug Delivery and Therapeutic Applications

    DEFF Research Database (Denmark)

    Hvilsted, Søren; Javakhishvili, Irakli; Bednarek, Melania

    2007-01-01

    of polymer blocks by “click chemistry”. An all polymerization strategy would imply preparing polymers by living/controlled techniques in such a manner that one block after polymerization can be converted to a macroinitiator enabling the second block to polymerize. The coupling strategy invariably inserts...... a linking unit, 1,4-triazol, resulting from the catalyzed, irreversible 1,3-dipolar cycloaddition reaction between an alkyne and an azide. Thus, this strategy necessitates the proper end functionalization of the polymeric building blocks. Fortunately the 1,4-triazol unit is FDA approved already existing...

  1. 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.

  2. Characterization of polymeric microneedle arrays for transdermal drug delivery.

    Directory of Open Access Journals (Sweden)

    Yusuf K Demir

    Full Text Available Microfabrication of dissolvable, swellable, and biodegradable polymeric microneedle arrays (MNs were extensively investigated based in a nano sensitive fabrication style known as micromilling that is then combined with conventional micromolding technique. The aim of this study was to describe the polymer selection, and optimize formulation compounding parameters for various polymeric MNs. Inverse replication of micromilled master MNs reproduced with polydimethylsiloxane (PDMS, where solid out of plane polymeric MNs were subsequently assembled, and physicochemically characterized. Dissolvable, swellable, and biodegradable MNs were constructed to depth of less than 1 mm with an aspect ratio of 3.6, and 1/2 mm of both inter needle tip and base spacing. Micromolding step also enabled to replicate the MNs very precisely and accurate. Polymeric microneedles (MN precision was ranging from ± 0.18 to ± 1.82% for microneedle height, ± 0.45 to ± 1.42% for base diameter, and ± 0.22 to ± 0.95% for interbase spacing. Although dissolvable sodium alginate MN showed less physical robustness than biodegradable polylactic-co-glycolic acid MN, their thermogravimetric analysis is of promise for constructing these polymeric types of matrix devices.

  3. REVIEW: CHITOSAN BASED HYDROGEL POLYMERIC BEADS – AS DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Manjusha Rani

    2010-11-01

    Full Text Available Chitosan obtained by alkaline deacetylation of chitin is a non-toxic, biocompatible, and biodegradable natural polymer. Chitosan-based hydrogel polymeric beads have been extensively studied as micro- or nano-particulate carriers in the pharmaceutical and medical fields, where they have shown promise for drug delivery as a result of their controlled and sustained release properties, as well as biocompatibility with tissue and cells. To introduce desired properties and enlarge the scope of the potential applications of chitosan, graft copolymerization with natural or synthetic polymers on it has been carried out, and also, various chitosan derivatives have been utilized to form beads. The desired kinetics, duration, and rate of drug release up to therapeutical level from polymeric beads are limited by specific conditions such as beads material and their composition, bead preparation method, amount of drug loading, drug solubility, and drug polymer interaction. The present review summarizes most of the available reports about compositional and structural effects of chitosan-based hydrogel polymeric beads on swelling, drug loading, and releasing properties. From the studies reviewed it is concluded that chitosan-based hydrogel polymeric beads are promising drug delivery systems.

  4. Physico-Chemical Strategies to Enhance Stability and Drug Retention of Polymeric Micelles for Tumor-Targeted Drug Delivery

    NARCIS (Netherlands)

    Shi, Y.; Lammers, Twan Gerardus Gertudis Maria; Storm, Gerrit; Hennink, W.E.

    2017-01-01

    Polymeric micelles (PM) have been extensively used for tumor-targeted delivery of hydrophobic anti-cancer drugs. The lipophilic core of PM is naturally suitable for loading hydrophobic drugs and the hydrophilic shell endows them with colloidal stability and stealth properties. Decades of research on

  5. Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies.

    Science.gov (United States)

    Mandal, Abhirup; Bisht, Rohit; Rupenthal, Ilva D; Mitra, Ashim K

    2017-02-28

    Effective intraocular drug delivery poses a major challenge due to the presence of various elimination mechanisms and physiological barriers that result in low ocular bioavailability after topical application. Over the past decades, polymeric micelles have emerged as one of the most promising drug delivery platforms for the management of ocular diseases affecting the anterior (dry eye syndrome) and posterior (age-related macular degeneration, diabetic retinopathy and glaucoma) segments of the eye. Promising preclinical efficacy results from both in-vitro and in-vivo animal studies have led to their steady progression through clinical trials. The mucoadhesive nature of these polymeric micelles results in enhanced contact with the ocular surface while their small size allows better tissue penetration. Most importantly, being highly water soluble, these polymeric micelles generate clear aqueous solutions which allows easy application in the form of eye drops without any vision interference. Enhanced stability, larger cargo capacity, non-toxicity, ease of surface modification and controlled drug release are additional advantages with polymeric micelles. Finally, simple and cost effective fabrication techniques render their industrial acceptance relatively high. This review summarizes structural frameworks, methods of preparation, physicochemical properties, patented inventions and recent advances of these micelles as effective carriers for ocular drug delivery highlighting their performance in preclinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. 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

  7. Production methodologies of polymeric and hydrogel particles for drug delivery applications.

    Science.gov (United States)

    Lima, Ana Catarina; Sher, Praveen; Mano, João F

    2012-02-01

    Polymeric particles are ideal vehicles for controlled delivery applications due to their ability to encapsulate a variety of substances, namely low- and high-molecular mass therapeutics, antigens or DNA. Micro and nano scale spherical materials have been developed as carriers for therapies, using appropriated methodologies, in order to achieve a prolonged and controlled drug administration. This paper reviews the methodologies used for the production of polymeric micro/nanoparticles. Emulsions, phase separation, spray drying, ionic gelation, polyelectrolyte complexation and supercritical fluids precipitation are all widely used processes for polymeric micro/nanoencapsulation. This paper also discusses the recent developments and patents reported in this field. Other less conventional methodologies are also described, such as the use of superhydrophobic substrates to produce hydrogel and polymeric particulate biomaterials. Polymeric drug delivery systems have gained increased importance due to the need for improving the efficiency and versatility of existing therapies. This allows the development of innovative concepts that could create more efficient systems, which in turn may address many healthcare needs worldwide. The existing methods to produce polymeric release systems have some critical drawbacks, which compromise the efficiency of these techniques. Improvements and development of new methodologies could be achieved by using multidisciplinary approaches and tools taken from other subjects, including nanotechnologies, biomimetics, tissue engineering, polymer science or microfluidics.

  8. PRELIMINARILY DEVELOPMENT OF A MOISTURE-ACTIVATED BIORESORBABLE POLYMERIC PLATFORM FOR DRUG DELIVERY

    Directory of Open Access Journals (Sweden)

    Renê O. do Couto

    2015-08-01

    Full Text Available Bioresorbable polymeric films were prepared by solvent casting using a tyrosine-derived polycarbonate and metronidazole (MDZ as the model drug at 2.5%, 5% and 10% (w/w. Drug loading did not affect the water uptake, drug release, polymer degradation or erosion profiles. All devices released approximately 85% (w/w of the drug within a 1.5 h period. This may be attributed to the rapid water uptake of the polymer. An increase in the water uptake correlated with a linear rate increase of the polymer degradation (0.968 ≤ R2 ≤ 0.999. Moreover, MDZ presented a remarkable plasticizing effect for the polymer and drug loading exerted a significant impact on the mechanical properties of the obtained films. The results obtained can be used to further the development of novel biocompatible and biodegradable polymeric platforms for the delivery of metronidazole and other drugs in a broad range of pharmaceutical applications.

  9. Aptamer-Mediated Polymeric Vehicles for Enhanced Cell-Targeted Drug Delivery.

    Science.gov (United States)

    Tan, Kei X; Danquah, Michael K; Sidhu, Amandeep; Yon, Lau Sie; Ongkudon, Clarence M

    2018-02-08

    The search for smart delivery systems for enhanced pre-clinical and clinical pharmaceutical delivery and cell targeting continues to be a major biomedical research endeavor owing to differences in the physicochemical characteristics and physiological effects of drug molecules, and this affects the delivery mechanisms to elicit maximum therapeutic effects. Targeted drug delivery is a smart evolution essential to address major challenges associated with conventional drug delivery systems. These challenges mostly result in poor pharmacokinetics due to the inability of the active pharmaceutical ingredients to specifically act on malignant cells thus, causing poor therapeutic index and toxicity to surrounding normal cells. Aptamers are oligonucleotides with engineered affinities to bind specifically to their cognate targets. Aptamers have gained significant interests as effective targeting elements for enhanced therapeutic delivery as they can be generated to specifically bind to wide range of targets including proteins, peptides, ions, cells and tissues. Notwithstanding, effective delivery of aptamers as therapeutic vehicles is challenged by cell membrane electrostatic repulsion, endonuclease degradation, low pH cleavage, and binding conformation stability. The application of molecularly engineered biodegradable and biocompatible polymeric particles with tunable features such as surface area and chemistry, particulate size distribution and toxicity creates opportunities to develop smart aptamer-mediated delivery systems for controlled drug release. This article discusses opportunities for particulate aptamer-drug formulations to advance current drug delivery modalities by navigating active ingredients through cellular and biomolecular traffic to target sites for sustained and controlled release at effective therapeutic dosages while minimizing systemic cytotoxic effects. A proposal for a novel drug-polymer-aptamer-polymer (DPAP) design of aptamer-drug formulation with

  10. 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

  11. Innovative polymeric system (IPS) for solvent-free lipophilic drug transdermal delivery via dissolving microneedles.

    Science.gov (United States)

    Dangol, Manita; Yang, Huisuk; Li, Cheng Guo; Lahiji, Shayan Fakhraei; Kim, Suyong; Ma, Yonghao; Jung, Hyungil

    2016-02-10

    Lipophilic drugs are potential drug candidates during drug development. However, due to the need for hazardous organic solvents for their solubilization, these drugs often fail to reach the pharmaceutical market, and in doing so highlight the importance of solvent free systems. Although transdermal drug delivery systems (TDDSs) are considered prospective safe drug delivery routes, a system involving lipophilic drugs in solvent free or powder form has not yet been described. Here, we report, for the first time, a novel approach for the delivery of every kind of lipophilic drug in powder form based on an innovative polymeric system (IPS). The phase transition of powder form of lipophilic drugs due to interior chemical bonds between drugs and biodegradable polymers and formation of nano-sized colloidal structures allowed the fabrication of dissolving microneedles (DMNs) to generate a powerful TDDS. We showed that IPS based DMN with powder capsaicin enhances the therapeutic effect for treatment of the rheumatic arthritis in a DBA/1 mouse model compared to a solvent-based system, indicating the promising potential of this new solvent-free platform for lipophilic drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Self-folding polymeric containers for encapsulation and delivery of drugs.

    Science.gov (United States)

    Fernandes, Rohan; Gracias, David H

    2012-11-01

    Self-folding broadly refers to self-assembly processes wherein thin films or interconnected planar templates curve, roll-up or fold into three dimensional (3D) structures such as cylindrical tubes, spirals, corrugated sheets or polyhedra. The process has been demonstrated with metallic, semiconducting and polymeric films and has been used to curve tubes with diameters as small as 2nm and fold polyhedra as small as 100nm, with a surface patterning resolution of 15nm. Self-folding methods are important for drug delivery applications since they provide a means to realize 3D, biocompatible, all-polymeric containers with well-tailored composition, size, shape, wall thickness, porosity, surface patterns and chemistry. Self-folding is also a highly parallel process, and it is possible to encapsulate or self-load therapeutic cargo during assembly. A variety of therapeutic cargos such as small molecules, peptides, proteins, bacteria, fungi and mammalian cells have been encapsulated in self-folded polymeric containers. In this review, we focus on self-folding of all-polymeric containers. We discuss the mechanistic aspects of self-folding of polymeric containers driven by differential stresses or surface tension forces, the applications of self-folding polymers in drug delivery and we outline future challenges. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Synthesis of click-reactive HPMA copolymers using RAFT polymerization for drug delivery applications

    DEFF Research Database (Denmark)

    Ebbesen, Morten F; Schaffert, D.H.; Crowley, Michael L

    2013-01-01

    This study describes a versatile strategy combining reversible addition fragmentation transfer (RAFT) polymerization and click chemistry to synthesize well-defined, reactive copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) for drug delivery applications. A novel azide containing monomer N-(3......-azidopropyl)methacrylamide (AzMA) was synthesized and copolymerized with HPMA using RAFT polymerization to provide p(HPMA-co-AzMA) copolymers with high control of molecular weight (∼10–54 kDa) and polydispersity (≤1.06). The utility of the side-chain azide functionality by Cu(I)-catalyzed azide...

  14. Amphiphilic polymeric micelles as the nanocarrier for peroral delivery of poorly soluble anticancer drugs.

    Science.gov (United States)

    Tian, Ye; Mao, Shirui

    2012-06-01

    Many amphiphilic copolymers have recently been synthesized as novel promising micellar carriers for the delivery of poorly water-soluble anticancer drugs. Studies on the formulation and oral delivery of such micelles have demonstrated their efficacy in enhancing drug uptake and absorption, and exhibit prolonged circulation time in vitro and in vivo. In this review, literature on hydrophobic modifications of several hydrophilic polymers, including polyethylene glycol, chitosan, hyaluronic acid, pluronic and tocopheryl polyethylene glycol succinate, is summarized. Parameters influencing the properties of polymeric micelles for oral chemotherapy are discussed and strategies to overcome main barriers for polymeric micelles peroral absorption are proposed. During the design of polymeric micelles for peroral chemotherapy, selecting or synthesizing copolymers with good compatibility with the drug is an effective strategy to increase drug loading and encapsulation efficiency. Stability of the micelles can be improved in different ways. It is recommended to take permeability, mucoadhesion, sustained release, and P-glycoprotein inhibition into consideration during copolymer preparation or to consider adding some excipients in the formulation. Furthermore, both the copolymer structure and drug loading methods should be controlled in order to get micelles with appropriate particle size for better absorption.

  15. A smart polymeric platform for multistage nucleus-targeted anticancer drug delivery.

    Science.gov (United States)

    Zhong, Jiaju; Li, Lian; Zhu, Xi; Guan, Shan; Yang, Qingqing; Zhou, Zhou; Zhang, Zhirong; Huang, Yuan

    2015-10-01

    Tumor cell nucleus-targeted delivery of antitumor agents is of great interest in cancer therapy, since the nucleus is one of the most frequent targets of drug action. Here we report a smart polymeric conjugate platform, which utilizes stimulus-responsive strategies to achieve multistage nuclear drug delivery upon systemic administration. The conjugates composed of a backbone based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer and detachable nucleus transport sub-units that sensitive to lysosomal enzyme. The sub-units possess a biforked structure with one end conjugated with the model drug, H1 peptide, and the other end conjugated with a novel pH-responsive targeting peptide (R8NLS) that combining the strength of cell penetrating peptide and nuclear localization sequence. The conjugates exhibited prolonged circulation time and excellent tumor homing ability. And the activation of R8NLS in acidic tumor microenvironment facilitated tissue penetration and cellular internalization. Once internalized into the cell, the sub-units were unleashed for nuclear transport through nuclear pore complex. The unique features resulted in 50-fold increase of nuclear drug accumulation relative to the original polymer-drug conjugates in vitro, and excellent in vivo nuclear drug delivery efficiency. Our report provides a strategy in systemic nuclear drug delivery by combining the microenvironment-responsive structure and detachable sub-units. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Partially polymerized liposomes: stable against leakage yet capable of instantaneous release for remote controlled drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Qin Guoting; Li Zheng; Xia Rongmin; Li Feng; O' Neill, Brian E; Li, King C [Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Goodwin, Jessica T; Khant, Htet A; Chiu, Wah, E-mail: zli@tmhs.org, E-mail: kli@tmhs.org [National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, TX 77030 (United States)

    2011-04-15

    A critical issue for current liposomal carriers in clinical applications is their leakage of the encapsulated drugs that are cytotoxic to non-target tissues. We have developed partially polymerized liposomes composed of polydiacetylene lipids and saturated lipids. Cross-linking of the diacetylene lipids prevents the drug leakage even at 40 deg. C for days. These inactivated drug carriers are non-cytotoxic. Significantly, more than 70% of the encapsulated drug can be instantaneously released by a laser that matches the plasmon resonance of the tethered gold nanoparticles on the liposomes, and the therapeutic effect was observed in cancer cells. The remote activation feature of this novel drug delivery system allows for precise temporal and spatial control of drug release.

  17. Recent advances in polymeric microspheres for parenteral drug delivery--part 1.

    Science.gov (United States)

    Mao, Shirui; Guo, Chunqiang; Shi, Yi; Li, Luk Chiu

    2012-09-01

    Polymeric microspheres have been established as a valuable parenteral drug delivery system for sustained release of therapeutic agents via subcutaneous or intramuscular injection. Biodegradable polymers which are either synthetic or from natural sources are reviewed with respect to recent advances in exploring their applications for microsphere fabrications. New information on the impact of formulation variables on the properties of microspheres formed by an emulsion method was also presented. The characterization of microspheres using advanced physical analytical techniques was also reviewed and the utilization of the information in assessing in vivo performance of the product was also highlighted. The broad clinical use of microspheres for delivery of therapeutic agents in particular biologics such as proteins has not been realized commercially. The limited availability of biodegradable polymers with a long history of regulatory approval and the challenges in gaining regulatory approval of a new polymer have hindered the development of microspheres for parenteral drug delivery.

  18. Nanotechnology-based polymeric bio(muco)adhesive platforms for controlling drug delivery - properties, methodologies and applications

    International Nuclear Information System (INIS)

    Carvalho, Flavia Chiva; Chorilli, Marlus; Gremiao, Maria Palmira Daflon

    2014-01-01

    Studies using bio(muco)adhesive drug delivery systems have recently gained great interest, which can promote drug targeting and more specific contact of the drug delivery system with the various absorptive membranes of the body. This technological platform associated with nanotechnology offers potential for controlling drug delivery; therefore, they are excellent strategies to increase the bioavailability of drugs. The objective of this work was to study nanotechnology-based polymeric bio(muco)adhesive platforms for controlling drug delivery, highlighting their properties, how the bio(muco)adhesion can be measured and their potential applications for different routes of administration. (author)

  19. Halloysite nanotubes-polymeric nanocomposites: characteristics, modifications and controlled drug delivery approaches

    Directory of Open Access Journals (Sweden)

    P. C. Ferrari

    Full Text Available Abstract Halloysite nanotubes (HNTs are aluminosilicate nanoclay mineral which have a hollow tubular structure and occurs naturally. They are biocompatible and viable carrier for inclusion of biologically active molecules due to the empty space inside the tubular structure. In this article, the HNTs main characteristics, and the HNTs-polymeric nanocomposite formation and their potential application as improvement of the mechanical performance of polymers and entrapment of hydrophilic and lipophilic substances are summarized. Recent works covering the increment of HNTs-polymeric nanocomposites and presenting promising employment of these systems as nanosized carrier, being suitable for pharmaceutical and biomedical applications, based on earlier evidence in literature of its nature to sustain the release of loaded drugs, presenting low cytotoxicity, and providing evidence for controlled drug delivery are reviewed.

  20. Novel local drug delivery system using thermoreversible gel in combination with polymeric microspheres or liposomes.

    Science.gov (United States)

    Arai, Takao; Benny, Ofra; Joki, Tatsuhiro; Menon, Lata G; Machluf, Marcelle; Abe, Toshiaki; Carroll, Rona S; Black, Peter M

    2010-04-01

    The purpose of our study was to evaluate the application of thermoreversible gelation polymer (TGP) as a local drug delivery system for malignant glioma. Polymeric microspheres or liposomes loaded with doxorubicin (sphere-dox or lipo-dox) were combined with TGP to provide continuous drug delivery of doxorubicin (dox) for kinetic release studies and cell viability assays on glioma cell lines in vitro. For in vivo studies, TGP loaded with dox alone (TGP-dox) was combined with sphere-dox or lipo-dox. Their antitumor effects on subcutaneous human glioma xenografts were evaluated in nude mice. In vitro, TGP combined with sphere-dox or lipo-dox released dox for up to 30 days. In vivo, TGP-dox combined with sphere-dox or lipo-dox inhibited subcutaneous glioma tumor growth until day 32 and day 38, respectively. TGP in combination with microspheres or liposomes successfully prolonged the release of dox and its antitumor effects.

  1. Multi-pulse drug delivery from a resorbable polymeric microchip device

    Science.gov (United States)

    Grayson, Amy C. Richards; Choi, Insung S.; Tyler, Betty M.; Wang, Paul P.; Brem, Henry; Cima, Michael J.; Langer, Robert

    2003-11-01

    Controlled-release drug delivery systems have many applications, including treatments for hormone deficiencies and chronic pain. A biodegradable device that could provide multi-dose drug delivery would be advantageous for long-term treatment of conditions requiring pulsatile drug release. In this work, biodegradable polymeric microchips were fabricated that released four pulses of radiolabelled dextran, human growth hormone or heparin in vitro. Heparin that was released over 142 days retained on average 96 +/- 12% of its bioactivity. The microchips were 1.2 cm in diameter, 480-560 μm thick and had 36 reservoirs that could each be filled with a different chemical. The devices were fabricated from poly(L-lactic acid) and had poly(D,L-lactic-co-glycolic acid) membranes of different molecular masses covering the reservoirs. A drug delivery system can be designed with the potential to release pulses of different drugs at intervals after implantation in a patient by using different molecular masses or materials for the membrane.

  2. Cell membrane-inspired polymeric micelles as carriers for drug delivery.

    Science.gov (United States)

    Liu, Gongyan; Luo, Quanqing; Gao, Haiqi; Chen, Yuan; Wei, Xing; Dai, Hong; Zhang, Zongcai; Ji, Jian

    2015-03-01

    In cancer therapy, surface engineering of drug delivery systems plays an essential role in their colloidal stability, biocompatibility and prolonged blood circulation. Inspired by the cell membrane consisting of phospholipids and glycolipids, a zwitterionic phosphorylcholine functionalized chitosan oligosaccharide (PC-CSO) was first synthesized to mimic the hydrophilic head groups of those amphipathic lipids. Then hydrophobic stearic acid (SA) similar to lipid fatty acids was grafted onto PC-CSO to form amphiphilic PC-CSO-SA copolymers. Cell membrane-mimetic micelles with a zwitterionic surface and a hydrophobic SA core were prepared by the self-assembly of PC-CSO-SA copolymers, showing excellent stability under extreme conditions including protein containing media, high salt content or a wide pH range. Doxorubicin (DOX) was successfully entrapped into polymeric micelles through the hydrophobic interaction between DOX and SA segments. After fast internalization by cancer cells, sustained drug release from micelles to the cytoplasm and nucleus was achieved. This result suggests that these biomimetic polymeric micelles may be promising drug delivery systems in cancer therapy.

  3. 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.

  4. 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.

  5. Biodegradable polymeric microsphere-based drug delivery for inductive browning of fat

    Directory of Open Access Journals (Sweden)

    Chunhui eJiang

    2015-11-01

    Full Text Available Brown and beige adipocytes are potent therapeutic agents to increase energy expenditure and reduce risks of obesity and its affiliated metabolic symptoms. One strategy to increase beige adipocyte content is through inhibition of the evolutionarily conserved Notch signaling pathway. However, systemic delivery of Notch inhibitors is associated with off-target effects and multiple dosages of application further faces technical and translational challenges. Here, we report the development of a biodegradable polymeric microsphere-based drug delivery system for sustained, local release of a Notch inhibitor, DBZ. The microsphere-based delivery system was fabricated and optimized using an emulsion/solvent evaporation technique to encapsulate DBZ into poly(lactide-co-glycolide (PLGA, a commonly used biodegradable polymer for controlled drug release. Release studies revealed the ability of PLGA microspheres to release DBZ in a sustained manner. Co-culture of white adipocytes with and without DBZ-loaded PLGA microspheres demonstrated that the released DBZ retained its bioactivity, and effectively inhibited Notch and promoted browning of white adipocytes. Injection of these DBZ-loaded PLGA microspheres into mouse inguinal white adipose tissue (WAT depots resulted in browning in vivo. Our results provide the encouraging proof-of-principle evidence for the application of biodegradable polymers as a controlled release platform for delivery of browning factors, and pave the way for development of new translational therapeutic strategies for treatment of obesity.

  6. Polymeric micellar pH-sensitive drug delivery system for doxorubicin.

    Science.gov (United States)

    Hrubý, Martin; Konák, Cestmír; Ulbrich, Karel

    2005-03-02

    A novel polymeric micellar pH-sensitive system for delivery of doxorubicin (DOX) is described. Polymeric micelles were prepared by self-assembly of amphiphilic diblock copolymers in aqueous solutions. The copolymers consist of a biocompatible hydrophilic poly(ethylene oxide) (PEO) block and a hydrophobic block containing covalently bound anthracycline antibiotic DOX. The starting block copolymers poly(ethylene oxide)-block-poly(allyl glycidyl ether) (PEO-PAGE) with a very narrow molecular weight distribution (Mw/Mn ca. 1.05) were prepared by anionic ring opening polymerization using sodium salt of poly(ethylene oxide) monomethyl ether as macroinitiator and allyl glycidyl ether as functional monomer. The copolymers were covalently modified via reactive double bonds by the addition of methyl sulfanylacetate. The resulting ester subsequently reacted with hydrazine hydrate yielding polymer hydrazide. The hydrazide was coupled with DOX yielding pH-sensitive hydrazone bonds between the drug and carrier. The resulting conjugate containing ca. 3 wt.% DOX forms micelles with Rh(a)=104 nm in phosphate-buffered saline. After incubation in buffers at 37 degrees C DOX was released faster at pH 5.0 (close to pH in endosomes; 43% DOX released within 24 h) than at pH 7.4 (pH of blood plasma; 16% DOX released within 24 h). Cleavage of hydrazone bonds between DOX and carrier continues even after plateau in the DOX release from micelles incubated in aqueous solutions is reached.

  7. New screening methodology for selection of polymeric materials for transdermal drug delivery devices

    Science.gov (United States)

    Falcone, Roberto P.

    As medical advances extend the human lifespan, the level of chronic illnesses will increase and thus straining the needs of the health care system that, as a result, governments will need to balance expenses without upsetting national budgets. Therefore, the selection of a precise and affordable drug delivery technology is seen as the most practical solution for governments, health care professionals, and consumers. Transdermal drug delivery patches (TDDP) are one of the best economical technologies that are favored by pharmaceutical companies and physicians alike because it offers fewer complications when compared to other delivery technologies. TDDP provides increased efficiency, safety and convenience for the patient. The TDDP segment within the US and Global drug delivery markets were valued at 5.6 and 12.7 billion respectively in 2009. TDDP is forecasted to reach $31.5 billion in 2015. The present TDDP technology involves the fabrication of a patch that consists of a drug embedded in a polymeric matrix. The diffusion coefficient is determined from the slope of the cumulative drug release versus time. It is a trial and error method that is time and labor consuming. With all the advantages that TDDPs can offer, the methodology used to achieve the so-called optimum design has resulted in several incidents where the safety and design have been put to question in recent times (e.g. Fentanyl). A more logical screening methodology is needed. This work shows the use of a modified Duda Zielinsky equation (DZE). Experimental release curves from commercial are evaluated. The experimental and theoretical Diffusion Coefficient values are found to be within the limits specified in the patent literature. One interesting finding is that the accuracy of the DZE is closer to experimental values when the type of Molecular Shape and Radius are used. This work shows that the modified DZE could be used as an excellent screening tool to determine the optimal polymeric matrices that

  8. Implantable and transdermal polymeric drug delivery technologies for the treatment of central nervous system disorders.

    Science.gov (United States)

    Govender, Thiresen; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Modi, Girish; Naidoo, Dinesh; Pillay, Viness

    2017-06-01

    The complexity of the brain and the membranous blood-brain barrier (BBB) has proved to be a significant limitation to the systemic delivery of pharmaceuticals to the brain rendering them sub-therapeutic and ineffective in the treatment of neurological diseases. Apart from this, lack of innovation in product development to counteract the problem is also a major contributing factor to a poor therapeutic outcome. Various innovative strategies show potential in treating some of the neurological disorders; however, drug delivery remains the most popular. To attain therapeutic drug levels in the central nervous system, large, intolerable systemic doses are generally administered. The major factors responsible for the success maintenance therapy of neurological diseases included controlled and sustained release of neurotherapeutics, reduced frequency of administration, higher bioavailability, and patient compliances. Conventional oral or injectable formulations cannot satisfy all the requirements in many circumstances. This article reviews the therapeutic implantable polymeric and transdermal devices employed in an attempt to effectively achieve therapeutic quantities of drug across the BBB over a prolonged period, to improve patient disease prognosis.

  9. 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

  10. Layer-by-layer assembled multilayers and polymeric nanoparticles for drug delivery in tissue engineering applications

    Science.gov (United States)

    Mehrotra, Sumit

    Tissues and organs in vivo are structured in three dimensional (3-D) ordered assemblies to maintain their metabolic functions. In the case of an injury, certain tissues lack the regenerative abilities without an external supportive environment. In order to regenerate the natural in vivo environment post-injury, there is a need to design three-dimensional (3-D) tissue engineered constructs of appropriate dimensions along with strategies that can deliver growth factors or drugs at a controlled rate from such constructs. This thesis focuses on the applications of hydrogen bonded (H-bonded) nanoscale layer-by-layer (LbL) assembled multilayers for time controlled drug delivery, fabrication of polymeric nanoparticles as drug delivery carriers, and engineering 3-D cellular constructs. Axonal regeneration in the central nervous system after spinal cord injury is often disorganized and random. To support linear axonal growth into spinal cord lesion sites, certain growth factors, such as brain-derived neurotrophic factor (BDNF), needs to be delivered at a controlled rate from an array of uniaxial channels patterned in a scaffold. In this study, we demonstrate for the first time that H-bonded LbL assembled degradable thin films prepared over agarose hydrogel, whereby the protein was loaded separately from the agarose fabrication, provided sustained release of protein under physiological conditions for more than four weeks. Further, patterned agarose scaffolds implanted at the site of a spinal cord injury forms a reactive cell layer of leptomeningeal fibroblasts in and around the scaffold. This limits the ability of axons to reinnervate the spinal cord. To address this challenge, we demonstrate the time controlled release of an anti-mitotic agent from agarose hydrdgel to control the growth of the reactive cell layer of fibroblasts. Challenges in tissue engineering can also be addressed using gene therapy approaches. Certain growth factors in the body are known to inhibit

  11. Polymeric micelles for drug targeting.

    Science.gov (United States)

    Mahmud, Abdullah; Xiong, Xiao-Bing; Aliabadi, Hamidreza Montazeri; Lavasanifar, Afsaneh

    2007-11-01

    Polymeric micelles are nano-delivery systems formed through self-assembly of amphiphilic block copolymers in an aqueous environment. The nanoscopic dimension, stealth properties induced by the hydrophilic polymeric brush on the micellar surface, capacity for stabilized encapsulation of hydrophobic drugs offered by the hydrophobic and rigid micellar core, and finally a possibility for the chemical manipulation of the core/shell structure have made polymeric micelles one of the most promising carriers for drug targeting. To date, three generations of polymeric micellar delivery systems, i.e. polymeric micelles for passive, active and multifunctional drug targeting, have arisen from research efforts, with each subsequent generation displaying greater specificity for the diseased tissue and/or targeting efficiency. The present manuscript aims to review the research efforts made for the development of each generation and provide an assessment on the overall success of polymeric micellar delivery system in drug targeting. The emphasis is placed on the design and development of ligand modified, stimuli responsive and multifunctional polymeric micelles for drug targeting.

  12. Cytocompatible chitosan-graft-mPEG-based 5-fluorouracil-loaded polymeric nanoparticles for tumor-targeted drug delivery.

    Science.gov (United States)

    Antoniraj, M Gover; Ayyavu, Mahesh; Henry, Linda Jeeva Kumari; Nageshwar Rao, Goutham; Natesan, Subramanian; Sundar, D Sathish; Kandasamy, Ruckmani

    2018-03-01

    Biodegradable materials like chitosan (CH) and methoxy polyethylene glycol (mPEG) are widely being used as drug delivery carriers for various therapeutic applications. In this study, copolymer (CH-g-mPEG) of CH and carboxylic acid terminated mPEG was synthesized by carbodiimide-mediated acid amine reaction. The resultant hydrophilic copolymer was characterized by Fourier transform infrared spectroscopy and 1 H NMR studies, revealing its relevant functional bands and proton peaks, respectively. Blank polymeric nanoparticles (B-PNPs) and 5-fluorouracil loaded polymeric nanoparticles (5-FU-PNPs) were formulated by ionic gelation method. Furthermore, folic acid functionalized FA-PNPs and FA-5-FU-PNPs were prepared for folate receptor-targeted drug delivery. FA-5-FU-PNPs were characterized by particle size, zeta potential, and in vitro drug release studies, resulting in 197.7 nm, +29.9 mv, and sustained drug release of 88% in 24 h, respectively. Cytotoxicity studies were performed for FA-PNPs and FA-5-FU-PNPs in MCF-7 cell line, which exhibited a cell viability of 80 and 41%, respectively. In vitro internalization studies were carried out for 5-FU-PNPs and FA-5-FU-PNPs which demonstrated increased cellular uptake of FA-5-FU-PNPs by receptor-mediated transport. Significant (p drug delivery, thereby influencing better therapeutic effect.

  13. Fabrication of luminescent hydroxyapatite nanorods through surface-initiated RAFT polymerization: Characterization, biological imaging and drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Heng, Chunning [Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R& D Center of Biomaterials and Fermentation Engineering, School of Chemical and Engineering, Northwest University, Xi’an, 710069 (China); Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Zheng, Xiaoyan [Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R& D Center of Biomaterials and Fermentation Engineering, School of Chemical and Engineering, Northwest University, Xi’an, 710069 (China); Liu, Meiying; Xu, Dazhuang; Huang, Hongye; Deng, Fengjie [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Hui, Junfeng, E-mail: huijunfeng@126.com [Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R& D Center of Biomaterials and Fermentation Engineering, School of Chemical and Engineering, Northwest University, Xi’an, 710069 (China); Zhang, Xiaoyong, E-mail: xiaoyongzhang1980@gmail.com [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wei, Yen, E-mail: weiyen@tsinghua.edu.cn [Department of Chemistry and the Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing, 100084 (China)

    2016-11-15

    Highlights: • Hydrophobic hydroxyapatite nanorods were obtained from hydrothermal synthesis. • Surface initiated RAFT polymerization was adopted to surface modification of hydroxyapatite nanorods. • These modified hydroxyapatite nanorods showed high water dispersibility and biocompatibility. • These modified hydroxyapatite nanorods can be used for controlled drug delivery. - Abstract: Hydroxyapatite nanomaterials as an important class of nanomaterials, have been widely applied for different biomedical applications for their excellent biocompatibility, biodegradation potential and low cost. In this work, hydroxyapatite nanorods with uniform size and morphology were prepared through hydrothermal synthesis. The surfaces of these hydroxyapatite nanorods are covered with hydrophobic oleic acid, making them poor dispersibility in aqueous solution and difficult for biomedical applications. To overcome this issue, a simple surface initiated polymerization strategy has been developed via combination of the surface ligand exchange and reversible addition fragmentation chain transfer (RAFT) polymerization. Hydroxyapatite nanorods were first modified with Riboflavin-5-phosphate sodium (RPSSD) via ligand exchange reaction between the phosphate group of RPSSD and oleic acid. Then hydroxyl group of nHAp-RPSSD was used to immobilize chain transfer agent, which was used as the initiator for surface-initiated RAFT polymerization. The nHAp-RPSSD-poly(IA-PEGMA) nanocomposites were characterized by means of {sup 1}H nuclear magnetic resonance, Fourier transform infrared spectroscopy, fluorescence spectroscopy and thermal gravimetric analysis in detailed. The biocompatibility, biological imaging and drug delivery of nHAp-RPSSD-poly(IA-PEGMA) were also investigated. Results showed that nHAp-RPSSD-poly(IA-PEGMA) exhibited excellent water dispersibility, desirable optical properties, good biocompatibility and high drug loading capability, making them promising candidates for

  14. Fabrication of luminescent hydroxyapatite nanorods through surface-initiated RAFT polymerization: Characterization, biological imaging and drug delivery applications

    International Nuclear Information System (INIS)

    Heng, Chunning; Zheng, Xiaoyan; Liu, Meiying; Xu, Dazhuang; Huang, Hongye; Deng, Fengjie; Hui, Junfeng; Zhang, Xiaoyong; Wei, Yen

    2016-01-01

    Highlights: • Hydrophobic hydroxyapatite nanorods were obtained from hydrothermal synthesis. • Surface initiated RAFT polymerization was adopted to surface modification of hydroxyapatite nanorods. • These modified hydroxyapatite nanorods showed high water dispersibility and biocompatibility. • These modified hydroxyapatite nanorods can be used for controlled drug delivery. - Abstract: Hydroxyapatite nanomaterials as an important class of nanomaterials, have been widely applied for different biomedical applications for their excellent biocompatibility, biodegradation potential and low cost. In this work, hydroxyapatite nanorods with uniform size and morphology were prepared through hydrothermal synthesis. The surfaces of these hydroxyapatite nanorods are covered with hydrophobic oleic acid, making them poor dispersibility in aqueous solution and difficult for biomedical applications. To overcome this issue, a simple surface initiated polymerization strategy has been developed via combination of the surface ligand exchange and reversible addition fragmentation chain transfer (RAFT) polymerization. Hydroxyapatite nanorods were first modified with Riboflavin-5-phosphate sodium (RPSSD) via ligand exchange reaction between the phosphate group of RPSSD and oleic acid. Then hydroxyl group of nHAp-RPSSD was used to immobilize chain transfer agent, which was used as the initiator for surface-initiated RAFT polymerization. The nHAp-RPSSD-poly(IA-PEGMA) nanocomposites were characterized by means of "1H nuclear magnetic resonance, Fourier transform infrared spectroscopy, fluorescence spectroscopy and thermal gravimetric analysis in detailed. The biocompatibility, biological imaging and drug delivery of nHAp-RPSSD-poly(IA-PEGMA) were also investigated. Results showed that nHAp-RPSSD-poly(IA-PEGMA) exhibited excellent water dispersibility, desirable optical properties, good biocompatibility and high drug loading capability, making them promising candidates for biological

  15. Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors

    DEFF Research Database (Denmark)

    Guo, Xiong; Zhao, Zhiyue; Chen, Dawei

    2018-01-01

    Co-delivery of anti-cancer drugs is promising to improve the efficacy of cancer treatment. This study was aiming to investigate the potential of concurrent delivery of resveratrol (RES) and docetaxel (DTX) via polymeric nanocarriers to treat breast cancer. To this end, methoxyl poly(ethylene glycol...... profiles, and enhanced cytotoxicity in vitro against MCF-7 cells. The AUC(0→t) of DTX and RES in mPEG-PDLA micelles after i.v. administration to rats were 3.0-fold and 1.6-fold higher than that of i.v. injections of the individual drugs. These findings indicated that the co-delivery of RES and DTX using m...

  16. 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.

  17. Development of novel hydrogels by modification of sterculia gum through radiation cross-linking polymerization for use in drug delivery

    International Nuclear Information System (INIS)

    Singh, Baljit; Vashishtha, Manu

    2008-01-01

    In order to modify the sterculia gum polysaccharide, to develop the hydrogels meant for the drug delivery, we have prepared sterculia gum, 2-hydroxyethylmethacrylate (HEMA) and acrylic acid (AAc) based hydrogels by radiation-induced crosslinking polymerization. Polymeric networks (hydrogels) thus formed were characterized with SEMs, FTIR,TGA and swelling studies which were carried out as a function monomers concentration, radiation dose, amount of sterculia contents in the polymer matrix and nature of the swelling medium. This paper discusses the swelling kinetics of the hydrogels and release dynamics of anti-diarrhea model drug ornidazole from the hydrogels to evaluation of swelling and drug release mechanism. Diffusion exponent 'n' have 0.73, 0.56 and 0.61 values and gel characteristic constant 'k' have 1.28 x 10 -2 , 2.95 x 10 -2 and 2.14 x 10 -2 values in distilled water, pH 2.2 buffer and pH 7.4 buffer. The release of drug from the polymer matrix occurred through non-Fickian diffusion mechanism. The values for the late time diffusion coefficients have been lower than the values of initial and average diffusion coefficients. It reflects that in the initial stages rate of release of drug from polymer matrix was higher as compared to the late stages, it means after certain time the drug release occurred in controlled manner

  18. Doxorubicin loaded Polymeric Nanoparticulate Delivery System to overcome drug resistance in osteosarcoma

    International Nuclear Information System (INIS)

    Susa, Michiro; Iyer, Arun K; Ryu, Keinosuke; Hornicek, Francis J; Mankin, Henry; Amiji, Mansoor M; Duan, Zhenfeng

    2009-01-01

    Drug resistance is a primary hindrance for the efficiency of chemotherapy against osteosarcoma. Although chemotherapy has improved the prognosis of osteosarcoma patients dramatically after introduction of neo-adjuvant therapy in the early 1980's, the outcome has since reached plateau at approximately 70% for 5 year survival. The remaining 30% of the patients eventually develop resistance to multiple types of chemotherapy. In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug resistant (MDR) tumor cells, we explored the possibility of loading doxorubicin onto biocompatible, lipid-modified dextran-based polymeric nanoparticles and evaluated the efficacy. Doxorubicin was loaded onto a lipid-modified dextran based polymeric nano-system. The effect of various concentrations of doxorubicin alone or nanoparticle loaded doxorubicin on KHOS, KHOS R2 , U-2OS, and U-2OS R2 cells was analyzed. Effects on drug retention, immunofluorescence, Pgp expression, and induction of apoptosis were also analyzed. Dextran nanoparticles loaded with doxorubicin had a curative effect on multidrug resistant osteosarcoma cell lines by increasing the amount of drug accumulation in the nucleus via Pgp independent pathway. Nanoparticles loaded with doxorubicin also showed increased apoptosis in osteosarcoma cells as compared with doxorubicin alone. Lipid-modified dextran nanoparticles loaded with doxorubicin showed pronounced anti-proliferative effects against osteosarcoma cell lines. These findings may lead to new treatment options for MDR osteosarcoma

  19. Activated Charge-Reversal Polymeric Nano-System: The Promising Strategy in Drug Delivery for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yichen Hu

    2016-04-01

    Full Text Available Various polymeric nanoparticles (NPs with optimal size, tumor-targeting functionalization, or microenvironment sensitive characteristics have been designed to solve several limitations of conventional chemotherapy. Nano-sized polymeric drug carrier systems have remarkably great advantages in drug delivery and cancer therapy, which are still plagued with severe deficiencies, especially insufficient cellular uptake. Recently, surface charge of medical NPs has been demonstrated to play an important role in cellular uptake. NPs with positive charge show higher affinity to anionic cell membranes such that with more efficient cellular internalization, but otherwise cause severe aggregation and fast clearance in circulation. Thus, surface charge-reversal NPs, specifically activated at the tumor site, have shown to elegantly resolve the enhanced cellular uptake in cancer cells vs. non-specific protein adsorption dilemma. Herein, this review mainly focuses on the effect of tumor-site activated surface charge reversal NPs on tumor treatment, including the activated mechanisms and various applications in suppressing cancer cells, killing cancer stem cell and overcoming multidrug resistance, with the emphasis on recent research in these fields. With the comprehensive and in-depth understanding of the activated surface charge reversal NPs, this approach might arouse great interest of scientific research on enhanced efficient polymeric nano-carriers in cancer therapy.

  20. Iterative photoinduced chain functionalization as a generic platform for advanced polymeric drug delivery systems

    Czech Academy of Sciences Publication Activity Database

    Al Samad, A.; Bethry, A.; Janoušková, Olga; Ciccione, J.; Wenk, C.; Coll, J.-L.; Subra, G.; Etrych, Tomáš; El Omar, F.; Bakkour, Y.; Coudane, J.; Nottelet, B.

    2018-01-01

    Roč. 39, č. 3 (2018), s. 1-5, č. článku 1700502. ISSN 1022-1336 R&D Projects: GA MŠk(CZ) LO1507; GA MŠk(CZ) LQ1604 Institutional support: RVO:61389013 Keywords : drug delivery systems * functionalization of polymers * photochemistry Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 4.265, year: 2016

  1. Evaluation of the functionality of biodegradable polymeric platforms for drug delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Gioti, M., E-mail: mgiot@physics.auth.gr; Karagkiozaki, V.; Basgiouraki, A.; Karagiannidis, P.G.; Logothetidis, S.

    2013-09-15

    We present the development of a drug-loaded triple-layer platform consisting of thin film biodegradable polymers, in a properly designed form for the desired gradual degradation. Poly(DL-lactide-co-glycolide) (PLGA (65:35), PLGA (75:25)) and polycaprolactone (PCL) were grown by spin coating technique, to synthesize the platforms with the order PCL/PLGA (75:25)/PLGA (65:35) that determine their degradation rates. The outer PLGA (65:35) layer was loaded with dipyridamole, an antiplatelet drug. Spectroscopic ellipsometry (SE) in the Vis-far UV range was used to determine the nanostructure, as well as the content of the incorporated drug in the as-grown platforms. In situ and real-time SE measurements were carried out using a liquid cell for the dynamic evaluation of the fibrinogen and albumin protein adsorption processes. Atomic force microscopy studies justified the SE results concerning the nanopores formation in the polymeric platforms, and the dominant adsorption mechanisms of the proteins, which were defined by the drug incorporation in the platforms.

  2. Study on Chitosan-Polyvinyl Alcohol Inter polymeric ph-Responsive Hydrogels for Controlled Drug Delivery

    International Nuclear Information System (INIS)

    Abdel-Bary, E.M.; El-Sherbiny, I.M.; Abdelaal, M.Y.; Abdel-Razik, E.A.

    2005-01-01

    Two series of ph-responsive biodegradable interpenetrating polymeric (IPN) hydrogels composed of chitosan and poly(vinyl alcohol) (PVA) were prepared for controlled drug release investigations. The first series was chemically crosslinked with different concentrations of glutaraldehyde as a crosslinked and the second series was crosslinked by gamma-radiation. Degree of crosslinking has been controlled by the concentration of crosslinked as well as by gamma irradiation dose. The equilibrium swelling -reflecting the degree of crosslinks - were carried out for the gels at 37 degree C in buffer solutions of ph 2.1 and 7.4 (simulated gastric and intestinal fluids respectively). 5-fluorouracil (5- FU) was entrapped, as a model therapeutic agent, in the hydrogels and equilibrium-swelling studies were carried out for the drug-entrapped gels at 37 degree C. The in-vitro release profiles of the drug were established at 37 degree C in ph 2.1 and 7.4. FT-IR was employed to investigate the structural changes of the gels with different degrees of crosslinking

  3. Development of self-forming doxorubicin-loaded polymeric depots as an injectable drug delivery system for liver cancer chemotherapy.

    Science.gov (United States)

    Nittayacharn, Pinunta; Nasongkla, Norased

    2017-07-01

    The objective of this work was to develop self-forming doxorubicin-loaded polymeric depots as an injectable drug delivery system for liver cancer chemotherapy and studied the release profiles of doxorubicin (Dox) from different depot formulations. Tri-block copolymers of poly(ε-caprolactone), poly(D,L-lactide) and poly(ethylene glycol) named PLECs were successfully used as a biodegradable material to encapsulate Dox as the injectable local drug delivery system. Depot formation and encapsulation efficiency of these depots were evaluated. Results show that depots could be formed and encapsulate Dox with high drug loading content. For the release study, drug loading content (10, 15 and 20% w/w) and polymer concentration (25, 30, and 35% w/v) were varied. It could be observed that the burst release occurred within 1-2 days and this burst release could be reduced by physical mixing of hydroxypropyl-beta-cyclodextrin (HP-β-CD) into the depot system. The degradation at the surface and cross-section of the depots were examined by Scanning Electron Microscope (SEM). In addition, cytotoxicity of Dox-loaded depots and blank depots were tested against human liver cancer cell lines (HepG2). Dox released from depots significantly exhibited potent cytotoxic effect against HepG2 cell line compared to that of blank depots. Results from this study reveals an important insight in the development of injectable drug delivery system for liver cancer chemotherapy. Schematic diagram of self-forming doxorubicin-loaded polymeric depots as an injectable drug delivery system and in vitro characterizations. (a) Dox-loaded PLEC depots could be formed with more than 90% of sustained-release Dox at 25% polymer concentration and 20% Dox-loading content. The burst release occurred within 1-2 days and could be reduced by physical mixing of hydroxypropyl-beta-cyclodextrin (HP-β-CD) into the depot system. (b) Dox released from depots significantly exhibited potent cytotoxic effect against human

  4. Development of Novel Polymeric Materials for Gene Therapy and pH-Sensitive Drug Delivery: Modeling, Synthesis, Characterization, and Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Brian Curtis [Iowa State Univ., Ames, IA (United States)

    2002-01-01

    The underlying theme of this thesis is the use of polymeric materials in bioapplications. Chapters 2-5 either develop a fundamental understanding of current materials used for bioapplications or establish protocols and procedures used in characterizing and synthesizing novel materials. In chapters 6 and 7 these principles and procedures are applied to the development of materials to be used for gene therapy and drug delivery. Chapter one is an introduction to the ideas that will be necessary to understand the subsequent chapters, as well as a literature review of these topics. Chapter two is a paper that has been published in the ''Journal of Controlled Release'' that examines the mechanism of drug release from a polymer gel, as well as experimental design suggestions for the evaluation of water soluble drug delivery systems. Chapter three is a paper that has been published in the ''Journal of Pharmaceutical Sciences'' that discusses the effect ionic salts have on properties of the polymer systems examined in chapter two. Chapter four is a paper published in the Materials Research Society Fall 2000 Symposium Series dealing with the design and synthesis of a pH-sensitive polymeric drug delivery device. Chapter five is a paper that has been published in the journal ''Biomaterials'' proposing a novel polymer/metal composite for use as a biomaterial in hip arthroplasty surgery. Chapter six is a paper that will appear in an upcoming volume of the Journal ''Biomaterials'' dealing with the synthesis of a novel water soluble cationic polymer with possible applications in non-viral gene therapy. Chapter seven is a paper that has been submitted to ''Macromolecules'' discussing several novel block copolymers based on poly(ethylene glycol) and poly(diethylamino ethyl methacrylate) that possess both pH-sensitive and temperature sensitive properties. Chapter eight contains a

  5. Graft polymerization of guar gum with acryl amide irradiated by microwaves for colonic drug delivery.

    Science.gov (United States)

    Shahid, Muhammad; Bukhari, Shazia Anwer; Gul, Yousra; Munir, Hira; Anjum, Fozia; Zuber, Mohammad; Jamil, Tahir; Zia, Khalid Mahmood

    2013-11-01

    This article is aimed to discuss the modification of guar gum through microwave irradiation by varying the time of irradiation. The characterization of the modified products was carried out using FTIR spectroscopic analysis. The FT-IR spectrum of the pure guar gum (GG) sample showed a broad peak at 3298 cm(-1) while the modified GG sample displayed a peak at 1541 cm(-1) which was absent in the crude sample. The X-ray diffraction (XRD) analysis confirmed the increase in crystallinity due to grafting of the sample with polyacrylamide (GG-g-PAM). Scanning electron microscope (SEM) images revealed that granular form of guar gum was changed into fibrillar structure after grafting. Thermo-gravimetric analysis of the modified samples was also carried out and discussed. The role of guar gum as a matrix for controlled release of drug triamcinolone was evaluated. The GG-acrylamide grafted samples presented a correlation between drug release and time of microwave exposure. The results revealed that such modified product has potential applications in colonic drug delivery system. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Monocyte-mediated delivery of polymeric backpacks to inflamed tissues: a generalized strategy to deliver drugs to treat inflammation.

    Science.gov (United States)

    Anselmo, Aaron C; Gilbert, Jonathan B; Kumar, Sunny; Gupta, Vivek; Cohen, Robert E; Rubner, Michael F; Mitragotri, Samir

    2015-02-10

    Targeted delivery of drugs and imaging agents to inflamed tissues, as in the cases of cancer, Alzheimer's disease, Parkinson's disease, and arthritis, represents one of the major challenges in drug delivery. Monocytes possess a unique ability to target and penetrate into sites of inflammation. Here, we describe a broad approach to take advantage of the natural ability of monocytes to target and deliver flat polymeric particles ("Cellular Backpacks") to inflamed tissues. Cellular backpacks attach strongly to the surface of monocytes but do not undergo phagocytosis due to backpack's size, disk-like shape and flexibility. Following attachment of backpacks, monocytes retain important cellular functions including transmigration through an endothelial monolayer and differentiation into macrophages. In two separate in vivo inflammation models, backpack-laden monocytes exhibit increased targeting to inflamed tissues. Cellular backpacks, and their abilities to attach to monocytes without impairing monocyte functions and 'hitchhike' to a variety of inflamed tissues, offer a new platform for both cell-mediated therapies and broad targeting of inflamed tissues. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Development of Surface-Variable Polymeric Nanoparticles for Drug Delivery to Tumors.

    Science.gov (United States)

    Han, Ning; Pang, Liang; Xu, Jun; Hyun, Hyesun; Park, Jinho; Yeo, Yoon

    2017-05-01

    To develop nanoparticle drug carriers that interact with cells specifically in the mildly acidic tumor microenvironment, we produced polymeric nanoparticles modified with amidated TAT peptide via a simple surface modification method. Two types of core poly(lactic-co-glycolic acid) nanoparticles (NL and NP) were prepared with a phospholipid shell as an optional feature and covered with polydopamine that enabled the conjugation of TAT peptide on the surface. Subsequent treatment with acid anhydrides such as cis-aconitic anhydride (CA) and succinic anhydride (SA) converted amines of lysine residues in TAT peptide to β-carboxylic amides, introducing carboxylic groups that undergo pH-dependent protonation and deprotonation. The nanoparticles modified with amidated TAT peptide (NLpT-CA and NPpT-CA) avoided interactions with LS174T colon cancer cells and J774A.1 macrophages at pH 7.4 but restored the ability to interact with LS174T cells at pH 6.5, delivering paclitaxel efficiently to the cells following a brief contact time. In LS174T tumor-bearing nude mice, NPpT-CA showed less accumulation in the lung than NPpT, reflecting the shielding effect of amidation, but tumor accumulation of NPpT and NPpT-CA was equally minimal. Comparison of particle stability and protein corona formation in media containing sera from different species suggests that NPpT-CA has been activated and opsonized in mouse blood to a greater extent than those in bovine serum-containing medium, thus losing the benefits of pH-sensitivity expected from in vitro experiments.

  8. Influence of serum albumin on intracellular delivery of drug-loaded hyaluronan polymeric micelles

    Czech Academy of Sciences Publication Activity Database

    Nešporová, K.; Sogorková, J.; Smejkalova, D.; Kulhánek, J.; Huerta-Angeles, G.; Kubala, Lukáš; Velebný, V.

    2016-01-01

    Roč. 511, č. 1 (2016), s. 638-647 ISSN 0378-5173 Institutional support: RVO:68081707 Keywords : Polymeric micelle * Hyaluronan * Fatty acid Subject RIV: BO - Biophysics Impact factor: 3.649, year: 2016

  9. pH- and temperature-sensitive polymeric microspheres for drug delivery: the dissolution of copolymers modulates drug release.

    Science.gov (United States)

    Fundueanu, Gheorghe; Constantin, Marieta; Stanciu, Cristina; Theodoridis, Georgios; Ascenzi, Paolo

    2009-12-01

    Most pH-/temperature-responsive polymers for controlled release of drugs are used as cross-linked hydrogels. However, the solubility properties of the linear polymers below and above the lower critical solution temperature (LCST) are not exploited. Here, the preparation and characterization of poly (N-isopropylacrylamide-co-methacrylic acid-co-methyl methacrylate) (poly (NIPAAm-co-MA-co-MM)) and poly (N-isopropylacrylamide-co-acrylamide) (poly (NIPAAm-co-AAm)), known as "smart" polymers (SP), is reported. Both poly (NIPAAm-co-MA-co-MM) and poly (NIPAAm-co-AAm) display pH- and temperature-responsive properties. Poly (NIPAAm-co-MA-co-MM) was designed to be insoluble in the gastric fluid (pH = 1.2), but soluble in the intestinal fluid (pH = 6.8 and 7.4), at the body temperature (37 degrees C). Poly (NIPAAm-co-AAm) was designed to have a lower critical solution temperature (LCST) corresponding to 37 degrees C at pH = 7.4, therefore it is not soluble above the LCST. The solubility characteristics of these copolymers were exploited to modulate the rate of release of drugs by changing pH and/or temperature. These copolymers were solubilized with hydrophobic cellulose acetate butyrate (CAB) and vitamin B(12) (taken as a water soluble drug model system) in an acetone/methanol mixture and dispersed in mineral oil. By a progressive evaporation of the solvent, the liquid droplets were transformed into loaded CAB/SP microspheres. Differential scanning calorimetric studies and scanning electron microscopy analysis demonstrated that the polymeric components of the microspheres precipitated separately during solvent evaporation forming small microdomains. Moreover, vitamin B(12) was found to be molecularly dispersed in both microdomains with no specific affinity for any polymeric component of microspheres. The release of vitamin B(12) was investigated as a function of temperature, pH, and the CAB/SP ratio.

  10. Magnetic Resonance Imaging of Polymeric Drug Delivery Systems in Breast Cancer Solid Tumors

    Science.gov (United States)

    2007-07-01

    isothiocyanatobenzyl-1,4,7,10 tetraazacyclododecane-1,4,7,10 tetraacetic acid (p-SCN-Bz-DOTA) in dry dimethylsulfoxide ( DMSO ). The p-SCN-Bz-DOTA was reacted at 1.2...APMA- benzyl-DOTA, and MA-GFLG-dox in predetermined molar compositions (Appendix 3, Table 1). All polymerization were carried out in acetone / DMSO ...using AIBN as the initiator. The ratio of monomers: initiator: solvent in the feed were kept constant at 12.5: 0.6: 86.9 (weight %), respectively

  11. Biophysical elucidation of the mechanism of enhanced drug release and topical delivery from polymeric film-forming systems.

    Science.gov (United States)

    Garvie-Cook, Hazel; Frederiksen, Kit; Petersson, Karsten; Guy, Richard H; Gordeev, Sergey N

    2015-08-28

    The effect of incorporating the lipidic medium-chain triglyceride (MCT) into polymeric film-forming systems (FFS) for topical drug delivery has been evaluated. First, the in vitro release of betamethasone-17-valerate (BMV), a representative dermatological drug, was determined from FFS comprising either hydrophobic polyacrylate co-polymers, or hydrophilic hydroxypropyl cellulose, with and without MCT. Release was enhanced from both polymers in the presence of MCT. Atomic force microscopy imaging and nanoindentation of FFS with MCT revealed two-phase structured films with softer inclusions (0.5 to 4μm in diameter) surrounded by a more rigid structure. Chemical mapping with Raman micro-spectroscopy showed that MCT was primarily confined to the inclusions within the polymer, which predominated in the surrounding film. BMV was distributed throughout the film but was more concentrated outside the inclusions. Furthermore, while BMV dissolved better into the hydrophobic films, it was more soluble in the MCT inclusions in hydrophilic films, suggesting its increased availability for diffusion from these softer regions of the polymer and explaining the release enhancement observed. Second, ex vivo skin penetration studies clearly revealed that uptake of BMV was higher from hydrophobic FFS than that from the more hydrophilic polymer due, at least in part, to the superior anti-nucleation efficiency of the former. Drug was quickly taken up into the SC from which it then diffused continuously over a sustained period into the lower, viable skin layers. In the presence of MCT, the overall uptake of BMV was increased and provides the basis for further optimisation of FFS as simple, convenient and sustained formulations for topical therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Synthesis and characterization of multifunctional hybrid-polymeric nanoparticles for drug delivery and multimodal imaging of cancer

    Directory of Open Access Journals (Sweden)

    Tng DJH

    2015-09-01

    nm nanoparticles and 9.79% for 110 nm nanoparticles. Finally, the study conducted in vivo revealed the importance of nanoparticle size selection for the effective delivery of drug formulations to the tumors. In agreement with our in vitro results, excellent uptake and retention were found in the tumors of MIA PaCa-2 tumor-bearing mice treated with 110 nm nanoparticles. Keywords: nanoparticles, individualized, cancer, multicellular tumor spheroids, hybrid-polymeric

  13. Polymeric particulate technologies for oral drug delivery and targeting: A pathophysiological perspective

    DEFF Research Database (Denmark)

    Hunter, A. Christy; Elsom, Jacqueline; Wibroe, Peter Popp

    2012-01-01

    Publication year: 2012 Source:Maturitas, Volume 73, Issue 1 A. Christy Hunter, Jacqueline Elsom, Peter P. Wibroe, S. Moein Moghimi The oral route for delivery of pharmaceuticals is the most widely used and accepted. Nanoparticles and microparticles are increasingly being applied within this arena....... It is the purpose of this review to describe these cutting edge technologies and specifically focus on the interaction and fate of these polymers within the gastrointestinal system....

  14. 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.

  15. PBCA-based polymeric microbubbles for molecular imaging and drug delivery

    NARCIS (Netherlands)

    Koczera, Patrick; Appold, Lia; Shi, Yang; Liu, Mengjiao; Dasgupta, Anshuman; Pathak, Vertika; Ojha, Tarun; Fokong, Stanley; Wu, Zhuojun; Van Zandvoort, Marc; Iranzo, Olga; Kuehne, Alexander J C; Pich, Andrij; Kiessling, Fabian; Lammers, Twan

    2017-01-01

    Microbubbles (MB) are routinely used as contrast agents for ultrasound (US) imaging. We describe different types of targeted and drug-loaded poly(n-butyl cyanoacrylate) (PBCA) MB, and demonstrate their suitability for multiple biomedical applications, including molecular US imaging and US-mediated

  16. Polymeric nanomedicines for image-guided drug delivery and tumor-targeted combination therapy

    Czech Academy of Sciences Publication Activity Database

    Lammers, T.; Šubr, Vladimír; Ulbrich, Karel; Hennink, W. E.; Storm, G.; Kiessling, F.

    2010-01-01

    Roč. 5, č. 3 (2010), s. 197-212 ISSN 1748-0132 R&D Projects: GA MŠk 1M0505 Institutional research plan: CEZ:AV0Z40500505 Keywords : nanomedicine s * drug targeting * polymer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 11.750, year: 2010

  17. Mucoadhesive drug delivery systems

    Directory of Open Access Journals (Sweden)

    Rahamatullah Shaikh

    2011-01-01

    Full Text Available Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal.

  18. Evaluation of nano encapsulation techniques in different polymeric system for the delivery of anti-tuberculosis drugs (ATD)

    CSIR Research Space (South Africa)

    Swai, H

    2006-02-01

    Full Text Available In this study, isoniazid, one of the most potent anti-TB drugs, was successfully encapsulated in poly (D, L- lactide-co-glycolide) (PLG) and in alginate-chitosan polymeric systems using a double-emulsion method and a cation-induced gelation method...

  19. Design of colon targeting drug delivery systems using natural polymeric carriers and their evaluation by gamma scintigraphy technique

    International Nuclear Information System (INIS)

    Soni, P.S.; Sawarkar, S.P.; Deshpande, S.G.; Bajaj, A.N.

    2004-01-01

    Of late, there has been a great awareness in the concept of drug targeting and delivery to a specific site (organ, tissue or cell) in the body to maximize therapeutic effect and reduce toxicity. The various approaches of site-specific drug delivery are implantable pumps, adhesive patches impregnated with drugs, vesicle enclosed drugs and drug carriers. Colonic drug delivery is intended for local and systemic treatment in the diseases of colon like inflammatory bowel conditions. Several approaches using viz. pro-drugs, biodegradable polymers and pH sensitive polymer coatings have been used to achieve colonic delivery. Natural polysaccarides like guar gum and pectin are promising candidates because they are susceptible to degradation by colonic bacteria and thus can release the entrapped drug in the colonic region. These indigenous natural polymers are cheaply and readily available. They comprise of polygalactouronic acid and refractory to host enzymes present in the upper gastrointestinal tract and are degraded by the enzymes produced by the colonic microflora. They were evaluated as a colonic carrier using 5-amino salicylic acid (5-ASA) as a model drug. After successful in vitro testing, gamma scintigraphy technique was used to assess in-vivo behavior of the colon specific drug delivery after a coat of Guar gum and Pectin

  20. Nanotechnology-based polymeric bio(muco)adhesive platforms for controlling drug delivery - properties, methodologies and applications; Plataformas bio(muco) adesivas polimericas baseadas em nanotecnologia para liberacao controlada de farmacos - propriedades, metodologias e aplicacoes

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, Flavia Chiva; Chorilli, Marlus; Gremiao, Maria Palmira Daflon, E-mail: pgremiao@fcfar.unesp.br [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Araraquara, SP (Brazil). Fac. de Ciencias Farmaceuticas. Dept. de Farmacos e Medicamentos

    2014-06-01

    Studies using bio(muco)adhesive drug delivery systems have recently gained great interest, which can promote drug targeting and more specific contact of the drug delivery system with the various absorptive membranes of the body. This technological platform associated with nanotechnology offers potential for controlling drug delivery; therefore, they are excellent strategies to increase the bioavailability of drugs. The objective of this work was to study nanotechnology-based polymeric bio(muco)adhesive platforms for controlling drug delivery, highlighting their properties, how the bio(muco)adhesion can be measured and their potential applications for different routes of administration. (author)

  1. Conjugated and Entrapped HPMA-PLA Nano-Polymeric Micelles Based Dual Delivery of First Line Anti TB Drugs: Improved and Safe Drug Delivery against Sensitive and Resistant Mycobacterium Tuberculosis.

    Science.gov (United States)

    Upadhyay, Seema; Khan, Iliyas; Gothwal, Avinash; Pachouri, Praveen K; Bhaskar, N; Gupta, Umesh D; Chauhan, Devendra S; Gupta, Umesh

    2017-09-01

    First line antiTB drugs have several physical and toxic manifestations which limit their applications. RIF is a hydrophobic drug and has low water solubility and INH is hepatotoxic. The main objective of the study was to synthesize, characterize HPMA-PLA co-polymeric micelles for the effective dual delivery of INH and RIF. HPMA-PLA co-polymer and HPMA-PLA-INH (HPI) conjugates were synthesized and characterized by FT-IR and 1 H-NMR spectroscopy. Later on RIF loaded HPMA-PLA-INH co-polymeric micelles (PMRI) were formulated and characterized for size, zeta potential and surface morphology (SEM, TEM) as well as critical micellar concentration. The safety was assessed through RBC's interaction study. The prepared PMRI were evaluated through MABA assay against sensitive and resistant strains of M. Tuberculosis. Size, zeta and entrapment efficiency for RIF loaded HPMA-PLA-INH polymeric micelles (PMRI) was 87.64 ± 1.98 nm, -19 ± 1.93 mV and 97.2 ± 1.56%, respectively. In vitro release followed controlled and sustained delivery pattern. Sustained release was also supported by release kinetics. Haemolytic toxicity of HPI and PMRI was 8.57 and 7.05% (p PLA polymeric micelles (PMRI) were more effective against sensitive and resistant M tuberculosis. The developed approach can lead to improved patient compliance and reduced dosing in future, offering improved treatment of tuberculosis.

  2. Development and Optimization of Polymeric Self-Emulsifying Nanocapsules for Localized Drug Delivery: Design of Experiment Approach

    Directory of Open Access Journals (Sweden)

    Jyoti Wadhwa

    2014-01-01

    Full Text Available The purpose of the present study was to formulate polymeric self-emulsifying curcumin nanocapsules with high encapsulation efficiency, good emulsification ability, and optimal globule size for localized targeting in the colon. Formulations were prepared using modified quasiemulsion solvent diffusion method. Concentration of formulation variables, namely, X1 (oil, X2 (polymeric emulsifier, and X3 (adsorbent, was optimized by design of experiments using Box-Behnken design, for its impact on mean globule size (Y1 and encapsulation efficiency (Y2 of the formulation. Polymeric nanocapsules with an average diameter of 100–180 nm and an encapsulation efficiency of 64.85 ± 0.12% were obtained. In vitro studies revealed that formulations released the drug after 5 h lag time corresponding to the time to reach the colonic region. Pronounced localized action was inferred from the plasma concentration profile (Cmax 200 ng/mL that depicts limited systemic absorption. Roentgenography study confirms the localized presence of carrier (0–2 h in upper GIT; 2–4 h in small intestine; and 4–24 h in the lower intestine. Optimized formulation showed significantly higher cytotoxicity (IC50 value 20.32 μM in HT 29 colonic cancer cell line. The present study demonstrates systematic development of polymeric self-emulsifying nanocapsule formulation of curcumin for localized targeting in colon.

  3. A Near-Infrared Photothermal Effect-Responsive Drug Delivery System Based on Indocyanine Green and Doxorubicin-Loaded Polymeric Micelles Mediated by Reversible Diels-Alder Reaction.

    Science.gov (United States)

    Li, Hui; Li, Junjie; Ke, Wendong; Ge, Zhishen

    2015-10-01

    Near-infrared light (NIR) possesses great advantages for light-responsive controllable drug release, such as deep tissue penetration and low damage to healthy tissues. Herein, a NIR-responsive drug delivery system is developed based on a NIR dye, indocyanine green (ICG), and anticancer drug, doxorubicin (DOX)-loaded thermoresponsive block copolymer micelles, in which the drug release can be controlled via NIR irradiation. First, block copolymers, poly(oligo(ethylene glycol) methacrylate)-block-poly(furfuryl methacrylate) (POEGMA-b-PFMA), are synthesized by sequential reversible addition-fragmentation chain-transfer (RAFT) polymerization, followed by modification with N-octyl maleimide through Diels-Alder (DA) reaction to produce POEGMA-b-POMFMA. The self-assembly of POEGMA-b-POMFMA by nano-precipitation in aqueous solution affords the polymeric micelles which are used to simultaneously encapsulate ICG and DOX. Upon irradiation by NIR light (805 nm), the loaded DOX is released rapidly from the micelles due to partial retro DA reaction and local temperature increase-induced faster drug diffusion by the photothermal effect. Cytotoxicity evaluation and intracellular distribution observation demonstrate significant synergistic effects of NIR-triggered drug release, photothermal, and chemotherapy toward cancer cells under NIR irradiation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Smart pH- and reduction-dual-responsive folate-PEG-coated polymeric lipid vesicles for tumor-triggered targeted drug delivery

    Science.gov (United States)

    Wang, Sheng; Wang, Hanjie; Liu, Zhongyun; Wang, Liangliang; Wang, Xiaomin; Su, Lin; Chang, Jin

    2014-06-01

    To improve their therapeutic index, designed nanocarriers should preferentially accumulate in tumor tissues and then rapidly enter tumor cells to release the encapsulated drugs in a triggered manner. In this article, a new kind of a smart pH- and reduction-dual-responsive drug delivery system based on folate-PEG-coated polymeric lipid vesicles (FPPLVs) formed from amphiphilic dextran derivatives was designed and prepared successfully. PEG chains with pH-sensitive hydrazone bonds, stearyl alcohol (SA) chains with reduction-sensitive disulfide bonds and folate were connected to a dextran main chain. The newly developed FPPLVs had a nano-sized structure (~50 nm) with a PEG coating. The in vitro DOX release profiles showed that the FPPLVs achieved a triggered drug release in response to acidic pH and reducing environments due to the cleavage of hydrazone bonds and disulfide bonds. It has also been demonstrated by an in vitro cellular uptake study that the FPPLVs lose their PEG coating as well as expose the folate in acidic conditions, which allows them to efficiently enter tumor cells through ligand-receptor interactions. In vitro cytotoxicity measurements also confirmed that FPPLVs exhibited pronounced antitumor activity against HeLa cells. These results suggest that FPPLVs are promising carriers for smart antitumor drug delivery applications.To improve their therapeutic index, designed nanocarriers should preferentially accumulate in tumor tissues and then rapidly enter tumor cells to release the encapsulated drugs in a triggered manner. In this article, a new kind of a smart pH- and reduction-dual-responsive drug delivery system based on folate-PEG-coated polymeric lipid vesicles (FPPLVs) formed from amphiphilic dextran derivatives was designed and prepared successfully. PEG chains with pH-sensitive hydrazone bonds, stearyl alcohol (SA) chains with reduction-sensitive disulfide bonds and folate were connected to a dextran main chain. The newly developed FPPLVs had a

  5. Graft Polymerization of Acryloyloxystarch with Poly(D,L-lactide) Macromonomer--A Potential Drug Delivery Carrier for Oral Administration

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ Starch is the second largest natural biopolymer. Its unique biodegradable and biocompatible properties make it be increasingly applied to the field of biomedicine[1~4]. As one kind of polysaccharide, starch is easily degraded into small organic molecules by amylase in the alimentary canal. The fact that the activity of amylase is restrained in the high acid environment in stomach provides an opportunity to prepare an intestinal-specific delivery carrier with starch. In order to protect the drugs that are sensitive to the enzyms in alimentary canal, a hydrophobic layer should be constructed between the outer bioadhensive shell and the drug.

  6. Preparation and in vitro characterization of SN-38-loaded, self-forming polymeric depots as an injectable drug delivery system.

    Science.gov (United States)

    Manaspon, Chawan; Hongeng, Suradej; Boongird, Atthaporn; Nasongkla, Norased

    2012-10-01

    This work describes the preparation and characterization of anticancer-loaded injectable polymeric depots that consisted of D,L-lactide (LA), ε-caprolactone (CL), and poly(ethylene glycol) (PEG) or [poly(ε-caprolactone)-random-poly(D,L-lactide)]-block-poly(ethylene glycol)-block-[poly(ε-caprolactone)-random-poly(D,L-lactide)] (PLEC) copolymers for malignant gliomas treatment. PLECs were polymerized with different percentages of LA to deliver 7-ethyl-10-hydroxycamptothecin (SN-38), a highly potent anticancer drug. SN-38-loaded depots could form directly in phosphate buffer saline with more than 98% encapsulation efficiency. The release rate of SN-38 from depots was found to depend on the amount of LA in PLECs, loading content of SN-38 in the depots, and depot weight. Encapsulation of SN-38 inside depots could enhance the stability of SN-38 where all of SN-38 released after 60 days was in an active form. Depots without SN-38 were evaluated as noncytotoxic against U-87MG, whereas SN-38-loaded depots showed cytotoxic effect as a function of concentration. Copyright © 2012 Wiley Periodicals, Inc.

  7. Neutral Polymeric Micelles for RNA Delivery

    Science.gov (United States)

    Lundy, Brittany B.; Convertine, Anthony; Miteva, Martina; Stayton, Patrick S.

    2013-01-01

    RNA interference (RNAi) drugs have significant therapeutic potential but delivery systems with appropriate efficacy and toxicity profiles are still needed. Here, we describe a neutral, ampholytic polymeric delivery system based on conjugatable diblock polymer micelles. The diblock copolymer contains a hydrophilic poly[N-(2-hydroxypropyl) methacrylamide-co-N-(2-(pyridin-2- yldisulfanyl)ethyl)methacrylamide) (poly[HPMA-co-PDSMA]) segment to promote aqueous stability and facilitate thiol-disulfide exchange reactions, and a second ampholytic block composed of propyl acrylic acid (PAA), dimethylaminoethyl methacrylate (DMAEMA), and butyl methacrylate (BMA). The poly[(HPMA-co-PDSMA)-b-(PAA-co-DMAEMA-co-BMA)] was synthesized using Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization with an overall molecular weight of 22,000 g/mol and a PDI of 1.88. Dynamic light scattering and fluorescence measurements indicated that the diblock copolymers self-assemble under aqueous conditions to form polymeric micelles with a hydrodynamic radius and critical micelle concentration of 25 nm and 25 μg/mL respectively. Red blood cell hemolysis experiments show that the neutral hydrophilic micelles have potent membrane destabilizing activity at endosomal pH values. Thiolated siRNA targeting glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was directly conjugated to the polymeric micelles via thiol exchange reactions with the pyridal disulfide groups present in the micelle corona. Maximum silencing activity in HeLa cells was observed at a 1:10 molar ratio of siRNA to polymer following a 48 h incubation period. Under these conditions 90 % mRNA knockdown and 65 % and protein knockdown of at 48 h was achieved with negligible toxicity. In contrast the polymeric micelles lacking a pH-responsive endosomalytic segment demonstrated negligible mRNA and protein knockdown under these conditions. The potent mRNA knockdown and excellent biocompatibility of the neutral siRNA conjugates

  8. Synthesis of mesoporous hollow silica nanospheres using polymeric micelles as template and their application as a drug-delivery carrier.

    Science.gov (United States)

    Sasidharan, Manickam; Zenibana, Haruna; Nandi, Mahasweta; Bhaumik, Asim; Nakashima, Kenichi

    2013-10-07

    Mesoporous hollow silica nanospheres with uniform particle sizes of 31-33 nm have been successfully synthesized by cocondensation of tetramethoxysilane (TMOS) and alkyltrimethoxysilanes [RSi(OR)3], where the latter also acts as a porogen. ABC triblock copolymer micelles of poly(styrene-b-2-vinyl pyridine-b-ethylene oxide) (PS-PVP-PEO) with a core-shell-corona architecture have been employed as a soft template at pH 4. The cationic shell block with 2-vinyl pyridine groups facilitates the condensation of silica precursors under the sol-gel reaction conditions. Phenyltrimethoxysilane, octyltriethoxysilane, and octadecyltriethoxysilanes were used as porogens for generating mesopores in the shell matrix of hollow silica and the octadecyl precursor produced the largest mesopore among the different porogens, of dimension ca. 4.1 nm. The mesoporous hollow particles were thoroughly characterized by small-angle X-ray diffraction (SXRD), thermal (TG/DTA) and nitrogen sorption analyses, infra-red (FTIR) and nuclear magnetic resonance ((13)C-CP MAS NMR and (29)Si MAS NMR) spectroscopies, and transmission electron microscopy (TEM). The mesoporous hollow silica nanospheres have been investigated for drug-delivery application by an in vitro method using ibuprofen as a model drug. The hollow silica nanospheres exhibited higher storage capacity than the well-known mesoporous silica MCM-41. Propylamine functionalized hollow particles show a more sustained release pattern than their unfunctionalized counterparts, suggesting a huge potential of hollow silica nanospheres in the controlled delivery of small drug molecules.

  9. Multifunctional reduction-responsive SPIO and DOX-loaded PEGylated polymeric lipid vesicles for magnetic resonance imaging-guided drug delivery

    International Nuclear Information System (INIS)

    Wang, Sheng; Yang, Weitao; Wang, Hanjie; Chang, Jin; Gong, Xiaoqun; Du, Hongli; Guo, Fangfang; Zhang, Bingbo

    2016-01-01

    Multifunctional superparamagnetic iron-oxide (SPIO)-based nanoparticles have been emerging as candidate nanosystems for cancer diagnosis and therapy. Here, we report the use of reduction- responsive SPIO/doxorubicin (DOX)-loaded poly(ethylene glycol) monomethyl ether (PEG)ylated polymeric lipid vesicles (SPIO and DOX-PPLVs) as a novel theranostic system for tumor magnetic resonance imaging (MRI) diagnosis and controlled drug delivery. These SPIO and DOX-PPLVs are composed of SPIOs that function as MR contrast agents for tumor enhancement and PPLVs as polymer matrices for encapsulating SPIO and antitumor drugs. The in vitro characterizations show that the SPIO and DOX-PPLVs have nanosized structures (∼80 nm), excellent colloidal stability,  good biocompatibility, as well as T _2-weighted MRI capability with a relatively high T _2 relaxivity (r _2 = 213.82 mM"−"1 s"−"1). In vitro drug release studies reveal that the release rate of DOX from the SPIO and DOX-PPLVs is accelerated in the reduction environment. An in vitro cellular uptake study and an antitumor study show that the SPIO and DOX-PPLVs have magnetic targeting properties and effective antitumor activity. In vivo studies show the SPIO and DOX-PPLVs have excellent T _2-weighted tumor targeted MRI capability, image-guided drug delivery capability, and high antitumor effects. These results suggest that the SPIO and DOX-PPLVs are promising nanocarriers for MRI diagnosis and cancer therapy applications. (paper)

  10. Development of self-assembled molecular structures on polymeric surfaces and their applications as ultrasonically responsive barrier coatings for on-demand, pulsatile drug delivery

    Science.gov (United States)

    Kwok, Connie Sau-Kuen

    Nature in the form of DNA, proteins, and cells has the remarkable ability to interact with its environment by processing biological information through specific molecular recognition at the interface. As such, materials that are capable of triggering an appropriate biological response need to be engineered at the biomaterial surface. Chemically and structurally well-defined self-assembled monolayers (SAMs), biomimetics of the lipid bilayer in cell membranes, have been created and studied mostly on rigid metallic surfaces. This dissertation is motivated by the lack of methods to generate a molecularly designed surface for biomedical polymers and thus provides an enabling technology to engineer a polymeric surface precisely at a molecular and cellular level. To take this innovation one step further, we demonstrated that such self-assembled molecular structure coated on drug-containing polymeric devices could act as a stimulus-responsive barrier for controlled drug delivery. A simple, one-step procedure for generating ordered, crystalline methylene chains on polymeric surfaces via urethane linkages was successfully developed. The self-assemblies and molecular structures of these crystalline methylene chains are comparable to the SAM model surfaces, as evidenced by various surface characterization techniques (XPS, TOF-SIMS, and FTIR-ATR). For the first time, these self-assembled molecular structures are shown to function collectively as an ultrasound-responsive barrier membrane for pulsatile drug delivery, including delivery of low-molecular-weight ciprofloxacin and high-molecular-weight insulin. Encouraging results, based on the insulin-activated deoxyglucose uptakes in adipocytes, indicate that the released insulin remained biologically active. Both chemical and acoustic analyses suggest that the ultrasound-assisted release mechanism is primarily induced by transient cavitation, which causes temporary disruption of the self-assembled overlayer, and thus allows

  11. Genetically engineered nanocarriers for drug delivery

    Directory of Open Access Journals (Sweden)

    Shi P

    2014-03-01

    Full Text Available Pu Shi, Joshua A Gustafson, J Andrew MacKayDepartment of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USAAbstract: Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins.Keywords: polymeric drug carrier, non-polymeric drug carrier, gene delivery, GE drug carriers

  12. Improving the drug delivery characteristics of graphene oxide based polymer nanocomposites through the “one-pot” synthetic approach of single-electron-transfer living radical polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Peng; Liu, Meiying; Tian, Jianwen; Deng, Fengjie [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wang, Ke [Department of Chemistry and the Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing 100084 (China); Xu, Dazhuang [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Liu, Liangji [Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006 (China); Zhang, Xiaoyong, E-mail: xiaoyongzhang1980@gmail.com [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wei, Yen, E-mail: weiyen@tsinghua.edu.cn [Department of Chemistry and the Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing 100084 (China)

    2016-08-15

    Graphical abstract: The PEGylated graphene oxides with high water dispersibility, good biocompatibility as well as high drug loading capability were fabricated via “one-pot” SET-LRP. - Highlights: • Surface modification of graphene oxide with polymers. • One-pot single-electron-transfer living radical polymerization. • Improving drug delivery characteristics. • The synthetic approach is rather simple, universal and effective. - Abstract: Graphene oxide (GO) based polymer nanocomposites have attracted extensive research interest recently for their outstanding physicochemical properties and potential applications. However, surface modification of GO with synthetic polymers has demonstrated to be trouble for most polymerization procedures are occurred under non-aqueous solution, which will in turn lead to the restacking of GO. In this work, a facile and efficient “one-pot” strategy has been developed for surface modification of GO with synthetic polymers through single-electron-transfer living radical polymerization (SET-LRP). The GO based polymer nanocomposites were obtained via SET-LRP in aqueous solution using poly(ethylene glycol) methyl ether methacrylate (PEGMA) as the monomer and 11-bromoundecanoic acid as the initiator, which could be effectively adsorbed on GO through hydrophobic interaction. The successful preparation of GO based polymer nanocomposites was confirmed by a series of characterization techniques such as {sup 1}H nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermogravimetric analysis, transmission electron microscopy and X-ray photoelectron spectroscopy. The resultant products exhibit high water disperisibility, excellent biocompatibility and high efficient drug loading capability, making these PEGylated GO nanocomposites promising candidates for biomedical applications.

  13. Soluble polymer conjugates for drug delivery.

    Science.gov (United States)

    Minko, Tamara

    2005-01-01

    The use of water-soluble polymeric conjugates as drug carriers offers several possible advantages. These advantages include: (1) improved drug pharmacokinetics; (2) decreased toxicity to healthy organs; (3) possible facilitation of accumulation and preferential uptake by targeted cells; (4) programmed profile of drug release. In this review, we will consider the main types of useful polymeric conjugates and their role and effectiveness as carriers in drug delivery systems.: © 2005 Elsevier Ltd . All rights reserved.

  14. 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.

  15. Transdermal drug delivery

    OpenAIRE

    Prausnitz, Mark R.; Langer, Robert

    2008-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability ...

  16. pH responsive cross-linked polymeric matrices based on natural polymers: effect of process variables on swelling characterization and drug delivery properties.

    Science.gov (United States)

    Naeem, Fahad; Khan, Samiullah; Jalil, Aamir; Ranjha, Nazar Muhammad; Riaz, Amina; Haider, Malik Salman; Sarwar, Shoaib; Saher, Fareha; Afzal, Samrin

    2017-01-01

    Introduction: The current work was aimed to design and synthesize novel crosslinked pH-sensitive gelatin/pectin (Ge/Pec) hydrogels using different polymeric ratios and to explore the effect of polymers and degree of crosslinking on dynamic, equilibrium swelling and in vitro release behavior of the model drug (Mannitol). Methods: The Ge/Pec based hydrogels were prepared using glutaraldehyde as the crosslinker. Various structural parameters that affect their release behavior were determined, including swelling study, porosity, sol-gel analysis, average molecular weight between crosslinks (Mc), volume fraction of polymer (V2,s), solvent interaction parameter (χ) and diffusion coefficient. The synthesized hydrogels were subjected to various characterization tools like Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and DSC differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Results: The hydrogels show highest water uptake and release at lower pH values. The FTIR spectra showed an interaction between Ge and Pec, and the drug-loaded samples also showed the drug-related peaks, indicating proper loading of the drug. DSC and TGA studies confirmed the thermal stability of hydrogel samples, while SEM showed the porous nature of hydrogels. The drug release followed non-Fickian diffusion or anomalous mechanism. Conclusion: Aforementioned characterizations reveal the successful formation of copolymer hydrogels. The pH-sensitive swelling ability and drug release behavior suggest that the rate of polymer chain relaxation and drug diffusion from these hydrogels are comparable which also predicts their possible use for site-specific drug delivery.

  17. pH responsive cross-linked polymeric matrices based on natural polymers: effect of process variables on swelling characterization and drug delivery properties

    Directory of Open Access Journals (Sweden)

    Fahad Naeem

    2017-08-01

    Full Text Available Introduction: The current work was aimed to design and synthesize novel crosslinked pH-sensitive gelatin/pectin (Ge/Pec hydrogels using different polymeric ratios and to explore the effect of polymers and degree of crosslinking on dynamic, equilibrium swelling and in vitro release behavior of the model drug (Mannitol. Methods: The Ge/Pec based hydrogels were prepared using glutaraldehyde as the crosslinker. Various structural parameters that affect their release behavior were determined, including swelling study, porosity, sol-gel analysis, average molecular weight between crosslinks (Mc, volume fraction of polymer (V2,s, solvent interaction parameter (χ and diffusion coefficient. The synthesized hydrogels were subjected to various characterization tools like Fourier transform infrared spectroscopy (FTIR, X-ray diffraction (XRD and DSC differential scanning calorimetry (DSC and scanning electron microscopy (SEM. Results: The hydrogels show highest water uptake and release at lower pH values. The FTIR spectra showed an interaction between Ge and Pec, and the drug-loaded samples also showed the drug-related peaks, indicating proper loading of the drug. DSC and TGA studies confirmed the thermal stability of hydrogel samples, while SEM showed the porous nature of hydrogels. The drug release followed non-Fickian diffusion or anomalous mechanism. Conclusion: Aforementioned characterizations reveal the successful formation of copolymer hydrogels. The pH-sensitive swelling ability and drug release behavior suggest that the rate of polymer chain relaxation and drug diffusion from these hydrogels are comparable which also predicts their possible use for site-specific drug delivery.

  18. Development and Characterization of Lecithin-based Self-assembling Mixed Polymeric Micellar (saMPMs) Drug Delivery Systems for Curcumin

    Science.gov (United States)

    Chen, Ling-Chun; Chen, Yin-Chen; Su, Chia-Yu; Wong, Wan-Ping; Sheu, Ming-Thau; Ho, Hsiu-O.

    2016-11-01

    Self-assembling mixed polymeric micelles (saMPMs) were developed for overcoming major obstacles of poor bioavailability (BA) associated with curcumin delivery. Lecithin added was functioned to enlarge the hydrophobic core of MPMs providing greater solubilization capacity. Amphiphilic polymers (sodium deoxycholate [NaDOC], TPGS, CREMOPHOR, or a PLURONIC series) were examined for potentially self-assembling to form MPMs (saMPMs) with the addition of lecithin. Particle size, size distribution, encapsulation efficacy (E.E.), and drug loading (D.L.) of the mixed micelles were optimally studied for their influences on the physical stability and release of encapsulated drugs. Overall, curcumin:lecithin:NaDOC and curcumin:lecithin:PLURONIC P123 in ratios of 2:1:5 and 5:2:20, respectively, were optimally obtained with a particle size of 80%, and a D.L. of >10%. The formulated system efficiently stabilized curcumin in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C and delayed the in vitro curcumin release. In vivo results further demonstrated that the slow release of curcumin from micelles and prolonged duration increased the curcumin BA followed oral and intravenous administrations in rats. Thus, lecithin-based saMPMs represent an effective curcumin delivery system, and enhancing BA of curcumin can enable its wide applications for treating human disorders.

  19. Transdermal drug delivery

    Science.gov (United States)

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

  20. Design, synthesis and evaluation of biotin decorated inulin-based polymeric micelles as long-circulating nanocarriers for targeted drug delivery.

    Science.gov (United States)

    Mandracchia, Delia; Rosato, Antonio; Trapani, Adriana; Chlapanidas, Theodora; Montagner, Isabella Monia; Perteghella, Sara; Di Franco, Cinzia; Torre, Maria Luisa; Trapani, Giuseppe; Tripodo, Giuseppe

    2017-04-01

    Here, long-circulating behaviors of Inulin-based nanomicelles are demonstrated for the first time in vivo. We show the synthesis and evaluation of biotin (BIO)-decorated polymeric INVITE micelles constituted of substances of natural origin, Inulin (INU) and Vitamin E (VITE), as long-circulating carriers for receptor-mediated targeted drug delivery. The resulting INVITE or INVITE-BIO micelles, nanometrically sized, did not reveal any cytotoxicity after 24h of incubation with Caco-2 cells. Moreover, in vitro studies on Caco-2 cells monolayers indicated that the transport of INVITE-BIO micelles was faster than surface unmodified INVITE micelles. In vivo optical imaging studies evidenced that, upon intravenous administration, INVITE-BIO micelles were quantitatively present in the body up to 48h. Instead, after oral administration, the micelles were not found in the systemic circulation but eliminated with the normal intestinal content. In conclusion, INVITE-BIO micelles may enhance drug accumulation in tumor-cells over-expressing the receptor for biotin through receptor mediated endocytosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. TRANSDERMAL DRUG DELIVERY SYSTEM: REVIEW

    OpenAIRE

    Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma

    2012-01-01

    Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...

  2. Eudragit ® FS 30 D polymeric films containing chondroitin sulfate as candidates for use in coating seeking modified delivery of drugs

    Directory of Open Access Journals (Sweden)

    Camila Borges dos Reis

    Full Text Available ABSTRACT Polymeric films associating different concentrations of Eudragit(r FS 30 D (EFS and chondroitin sulfate (CS were produced by casting for the development of a new target-specific site material. Formed films kept a final polymer mass of 4% (w/v in the following proportions: EFS 100:00 CS (control, EFS 95:05 CS, EFS 90:10 CS and EFS 80:20 CS. They were analyzed for physical and chemical characteristics using Fourier transform infrared spectroscopy (FTIR, scanning electron microscopy (SEM and Raman spectroscopy. Furthermore, they were characterized by their water vapor permeability and degree of hydration at different conditions simulating the gastrointestinal tract. No chemical interactions were observed between CS and EFS, suggesting only a physical interaction between them in the different combinations tested. The results suggest that EFS and CS, when combined, may form films that are candidates for coating processes seeking a modified drug delivery, especially due to the synergism between pH dependency and specific biodegradability properties by the colonic microbiota. EFS 90:10 CS proved to be the most suitable for this purpose considering hydration and permeability characteristics of different associations analyzed.

  3. Smart Polymers in Nasal Drug Delivery.

    Science.gov (United States)

    Chonkar, Ankita; Nayak, Usha; Udupa, N

    2015-01-01

    Nasal drug delivery has now been recognized as a promising route for drug delivery due to its capability of transporting a drug to systemic circulation and central nervous system. Though nasal mucosa offers improved bioavailability and quick onset of action of the drug, main disadvantage associated with nasal drug delivery is mucocilliary clearance due to which drug particles get cleared from the nose before complete absorption through nasal mucosa. Therefore, mucoadhesive polymeric approach can be successfully used to enhance the retention of the drug on nasal mucosal surface. Here, some of the aspects of the stimuli responsive polymers have been discussed which possess liquid state at the room temperature and in response to nasal temperature, pH and ions present in mucous, can undergo in situ gelation in nasal cavity. In this review, several temperature responsive, pH responsive and ion responsive polymers used in nasal delivery, their gelling mechanisms have been discussed. Smart polymers not only able to enhance the retention of the drug in nasal cavity but also provide controlled release, ease of administration, enhanced permeation of the drug and protection of the drug from mucosal enzymes. Thus smart polymeric approach can be effectively used for nasal delivery of peptide drugs, central nervous system dugs and hormones.

  4. Drug delivery and formulations.

    Science.gov (United States)

    Breitkreutz, Jörg; Boos, Joachim

    2011-01-01

    Paediatric drug delivery is a major challenge in drug development. Because of the heterogeneous nature of the patient group, ranging from newborns to adolescents, there is a need to use appropriate excipients, drug dosage forms and delivery devices for different age groups. So far, there is a lack of suitable and safe drug formulations for children, especially for the very young and seriously ill patients. The new EU legislation will enforce paediatric clinical trials and drug development. Current advances in paediatric drug delivery include interesting new concepts such as fast-dissolving drug formulations, including orodispersible tablets and oral thin strips (buccal wafers), and multiparticulate dosage forms based on mini-tabletting or pelletization technologies. Parenteral administration is likely to remain the first choice for children in the neonatal period and for emergency cases. Alternative routes of administration include transdermal, pulmonary and nasal drug delivery systems. A few products are already available on the market, but others still need further investigations and clinical proof of concept.

  5. Microfabrication for Drug Delivery

    Science.gov (United States)

    Koch, Brendan; Rubino, Ilaria; Quan, Fu-Shi; Yoo, Bongyoung; Choi, Hyo-Jick

    2016-01-01

    This review is devoted to discussing the application of microfabrication technologies to target challenges encountered in life processes by the development of drug delivery systems. Recently, microfabrication has been largely applied to solve health and pharmaceutical science issues. In particular, fabrication methods along with compatible materials have been successfully designed to produce multifunctional, highly effective drug delivery systems. Microfabrication offers unique tools that can tackle problems in this field, such as ease of mass production with high quality control and low cost, complexity of architecture design and a broad range of materials. Presented is an overview of silicon- and polymer-based fabrication methods that are key in the production of microfabricated drug delivery systems. Moreover, the efforts focused on studying the biocompatibility of materials used in microfabrication are analyzed. Finally, this review discusses representative ways microfabrication has been employed to develop systems delivering drugs through the transdermal and oral route, and to improve drug eluting implants. Additionally, microfabricated vaccine delivery systems are presented due to the great impact they can have in obtaining a cold chain-free vaccine, with long-term stability. Microfabrication will continue to offer new, alternative solutions for the development of smart, advanced drug delivery systems. PMID:28773770

  6. Supersaturating drug delivery systems

    DEFF Research Database (Denmark)

    Laitinen, Riikka; Löbmann, Korbinian; Grohganz, Holger

    2017-01-01

    of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading......Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement...... strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition...

  7. An overview of polymeric dosage forms in buccal drug delivery: State of art, design of formulations and their in vivo performance evaluation.

    Science.gov (United States)

    Fonseca-Santos, Bruno; Chorilli, Marlus

    2018-05-01

    Owing to the ease of the administration, the oral cavity is an attractive site for the delivery of drugs. The main difficulty for administration via the buccal route is an effective physiological removal mechanism of the oral cavity that takes way the formulation from the buccal site and decreases the bioavailability of drugs. The use of mucoadhesive polymers in buccal drug delivery shows assessing buccal drug permeation and absorption, however some studies bring an in vivo performance. This review points to the use of polymers in the manufacture of drug delivery systems (hydrogels, films and tablets) and shows the results of their in vivo performance tests. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery.

    Science.gov (United States)

    Mahlumba, Pakama; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

    2016-07-30

    Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of proteins and peptides, including large size, short half-life, capability to provoke immune responses and susceptibility to degradation. Various delivery routes and delivery systems have been utilized to improve bioavailability, patient acceptability and reduce biodegradation. The ocular route remains of great interest, particularly for responsive delivery of macromolecules due to the anatomy and physiology of the eye that makes it a sensitive and complex environment. Research in this field is slowly gaining attention as this could be the breakthrough in ocular drug delivery of macromolecules. This work reviews stimuli-responsive polymeric delivery systems, their use in the delivery of therapeutic proteins and peptides as well as examples of proteins and peptides used in the treatment of ocular disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound and magnetic field. In addition, it discusses the current progress in responsive ocular drug delivery. Furthermore, it explores future prospects in the use of stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli-responsive polymers offer great potential in improving the delivery of ocular therapeutics, therefore there is a need to consider them in order to guarantee a local, sustained and ideal delivery of ocular proteins and peptides, evading tissue invasion and systemic side-effects.

  9. MRI in ocular drug delivery

    OpenAIRE

    Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

    2008-01-01

    Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery de...

  10. Thiolated polymers as mucoadhesive drug delivery systems.

    Science.gov (United States)

    Duggan, Sarah; Cummins, Wayne; O' Donovan, Orla; Hughes, Helen; Owens, Eleanor

    2017-03-30

    Mucoadhesion is the process of binding a material to the mucosal layer of the body. Utilising both natural and synthetic polymers, mucoadhesive drug delivery is a method of controlled drug release which allows for intimate contact between the polymer and a target tissue. It has the potential to increase bioavailability, decrease potential side effects and offer protection to more sensitive drugs such as proteins and peptide based drugs. The thiolation of polymers has, in the last number of years, come to the fore of mucoadhesive drug delivery, markedly improving mucoadhesion due to the introduction of free thiol groups onto the polymer backbone while also offering a more cohesive polymeric matrix for the slower and more controlled release of drug. This review explores the concept of mucoadhesion and the recent advances in both the polymers and the methods of thiolation used in the synthesis of mucoadhesive drug delivery devices. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Hydrogel nanoparticles in drug delivery.

    Science.gov (United States)

    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.

  12. Microcontainers - an oral drug delivery system for poorly soluble drugs

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Petersen, Ritika Singh; Marizza, Paolo

    In oral delivery, it can sometimes be necessary to employ drug delivery systems to achieve targeted delivery to the intestine. Microcontainers are polymeric, cylindrical devices in the micrometer size range (Figure 1), and are suggested as a promising oral drug delivery system [1],[2]. The purpose...... of these studies was to fabricate microcontainers in either SU-8 or biodegradable poly-L-lactic acid (PLLA), and fill the microcontainers with poorly soluble drugs. Furthermore, the application of the microcontainers as an oral drug delivery system was investigated in terms of release, in situ intestinal perfusion...... medium at pH 6.5 was observed. In situ intestinal perfusions were performed in rats of the Eudragit-coated ASSF-filled microcontainers and compared to a furosemide solution. At the end of the study, the small intestine was harvested from the rat and imaged under a light microscope. The absorption rate...

  13. Dendrimers for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Abhay Singh Chauhan

    2018-04-01

    Full Text Available Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine (PAMAM dendrimers in 1985. Application of dendrimers as a drug delivery system started in late 1990s. Dendrimers for drug delivery are employed using two approaches: (i formulation and (ii nanoconstruct. In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. We have demonstrated the utility of PAMAM dendrimers for enhancing solubility, stability and oral bioavailability of various drugs. Drug entrapment and drug release from dendrimers can be controlled by modifying dendrimer surfaces and generations. PAMAM dendrimers are also shown to increase transdermal permeation and specific drug targeting. Dendrimer platforms can be engineered to attach targeting ligands and imaging molecules to create a nanodevice. Dendrimer nanotechnology, due to its multifunctional ability, has the potential to create next generation nanodevices.

  14. Drug delivery through microneedles

    NARCIS (Netherlands)

    Luttge, R.; Dietzel, A.

    2016-01-01

    Drug delivery through microneedles is a new form of a pharmaceutical dosage system. While single microneedles have been clinically applied already, the out-of-plane integration of a multitude of microneedles in a pharmaceutical patch is a disruptive technology. To take advantage of micro- and

  15. Evaluation of a combined drug-delivery system for proteins assembled with polymeric nanoparticles and porous microspheres; characterization and protein integrity studies.

    Science.gov (United States)

    Alcalá-Alcalá, Sergio; Benítez-Cardoza, Claudia G; Lima-Muñoz, Enrique J; Piñón-Segundo, Elizabeth; Quintanar-Guerrero, David

    2015-07-15

    This work presents an evaluation of the adsorption/infiltration process in relation to the loading of a model protein, α-amylase, into an assembled biodegradable polymeric system, free of organic solvents and made up of poly(D,L-lactide-co-glycolide) acid (PLGA). Systems were assembled in a friendly aqueous medium by adsorbing and infiltrating polymeric nanoparticles into porous microspheres. These assembled systems are able to load therapeutic amounts of the drug through adsorption of the protein onto the large surface area characteristic of polymeric nanoparticles. The subsequent infiltration of nanoparticles adsorbed with the protein into porous microspheres enabled the controlled release of the protein as a function of the amount of infiltrated nanoparticles, since the surface area available on the porous structure is saturated at different levels, thus modifying the protein release rate. Findings were confirmed by both the BET technique (N2 isotherms) and in vitro release studies. During the adsorption process, the pH of the medium plays an important role by creating an environment that favors adsorption between the surfaces of the micro- and nano-structures and the protein. Finally, assays of α-amylase activity using 2-chloro-4-nitrophenyl-α-D-maltotrioside (CNP-G3) as the substrate and the circular dichroism technique confirmed that when this new approach was used no conformational changes were observed in the protein after release. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Nanocomposite thin films for triggerable drug delivery.

    Science.gov (United States)

    Vannozzi, Lorenzo; Iacovacci, Veronica; Menciassi, Arianna; Ricotti, Leonardo

    2018-05-01

    Traditional drug release systems normally rely on a passive delivery of therapeutic compounds, which can be partially programmed, prior to injection or implantation, through variations in the material composition. With this strategy, the drug release kinetics cannot be remotely modified and thus adapted to changing therapeutic needs. To overcome this issue, drug delivery systems able to respond to external stimuli are highly desirable, as they allow a high level of temporal and spatial control over drug release kinetics, in an operator-dependent fashion. Areas covered: On-demand drug delivery systems actually represent a frontier in this field and are attracting an increasing interest at both research and industrial level. Stimuli-responsive thin films, enabled by nanofillers, hold a tremendous potential in the field of triggerable drug delivery systems. The inclusion of responsive elements in homogeneous or heterogeneous thin film-shaped polymeric matrices strengthens and/or adds intriguing properties to conventional (bare) materials in film shape. Expert opinion: This Expert Opinion review aims to discuss the approaches currently pursued to achieve an effective on-demand drug delivery, through nanocomposite thin films. Different triggering mechanisms allowing a fine control on drug delivery are described, together with current challenges and possible future applications in therapy and surgery.

  17. Biomimetics in drug delivery systems: A critical review.

    Science.gov (United States)

    Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh

    2017-05-10

    Today, the advanced drug delivery systems have been focused on targeted drug delivery fields. The novel drug delivery is involved with the improvement of the capacity of drug loading in drug carriers, cellular uptake of drug carriers, and the sustained release of drugs within target cells. In this review, six groups of therapeutic drug carriers including biomimetic hydrogels, biomimetic micelles, biomimetic liposomes, biomimetic dendrimers, biomimetic polymeric carriers and biomimetic nanostructures, are studied. The subject takes advantage of the biomimetic methods of productions or the biomimetic techniques for the surface modifications, similar to what accrues in natural cells. Moreover, the effects of these biomimetic approaches for promoting the drug efficiency in targeted drug delivery are visible. The study demonstrates that the fabrication of biomimetic nanocomposite drug carriers could noticeably promote the efficiency of drugs in targeted drug delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. One-step shell polymerization of inorganic nanoparticles and their applications in SERS/nonlinear optical imaging, drug delivery, and catalysis.

    Science.gov (United States)

    Liu, Tzu-Ming; Yu, Jiashing; Chang, C Allen; Chiou, Arthur; Chiang, Huihua Kenny; Chuang, Yu-Chun; Wu, Cheng-Han; Hsu, Che-Hao; Chen, Po-An; Huang, Chih-Chia

    2014-07-07

    Surface functionalized nanoparticles have found their applications in several fields including biophotonics, nanobiomedicine, biosensing, drug delivery, and catalysis. Quite often, the nanoparticle surfaces must be post-coated with organic or inorganic layers during the synthesis before use. This work reports a generally one-pot synthesis method for the preparation of various inorganic-organic core-shell nanostructures (Au@polymer, Ag@polymer, Cu@polymer, Fe3O4@polymer, and TiO2@polymer), which led to new optical, magnetic, and catalytic applications. This green synthesis involved reacting inorganic precursors and poly(styrene-alt-maleic acid). The polystyrene blocks separated from the external aqueous environment acting as a hydrophobic depot for aromatic drugs and thus illustrated the integration of functional nanoobjects for drug delivery. Among these nanocomposites, the Au@polymer nanoparticles with good biocompatibility exhibited shell-dependent signal enhancement in the surface plasmon resonance shift, nonlinear fluorescence, and surface-enhanced Raman scattering properties. These unique optical properties were used for dual-modality imaging on the delivery of the aromatic photosensitizer for photodynamic therapy to HeLa cells.

  19. In vitro and ex vivo evaluation of polymeric nanoparticles for vaginal and rectal delivery of the anti-HIV drug dapivirine.

    Science.gov (United States)

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

    2013-07-01

    Prevention strategies such as the development of microbicides are thought to be valuable in the fight against HIV/AIDS. Despite recent achievements, there is still a long road ahead in the field, particularly at the level of drug formulation. Drug nanocarriers based on polymers may be useful in enhancing local drug delivery while limiting systemic exposure. We prepared differently surface-engineered poly(ε-caprolactone) (PCL) nanoparticles (NPs) and tested their ability to modulate the permeability and retention of dapivirine in cell monolayers and pig vaginal and rectal mucosa. NPs coated with poly(ethylene oxide) (PEO) were shown able to reduce permeability across monolayers/tissues, while modification of nanosystems with cetyl trimethylammonium bromide (CTAB) enhanced transport. In the case of coating NPs with sodium lauryl sulfate (SLS), dapivirine permeability was unchanged. All NPs increased monolayer/tissue drug retention as compared to unformulated dapivirine. This fact was associated, at least partially, to the ability of NPs to be taken up by cells or penetrate mucosal tissue. Cell and tissue toxicity was also affected differently by NPs: PEO modification decreased the in vitro (but not ex vivo) toxicity of dapivirine, while higher toxicity was generally observed for NPs coated with SLS or CTAB. Overall, presented results support that PCL nanoparticles are capable of modulating drug permeability and retention in cell monolayers and mucosal tissues relevant for vaginal and rectal delivery of microbicides. In particular, PEO-modified dapivirine-loaded PCL NPs may be advantageous in increasing drug residence at epithelial cell lines/mucosal tissues, which may potentially increase the efficacy of microbicide drugs.

  20. Controlled drug delivery systems towards new frontiers in patient care

    CERN Document Server

    Rossi, Filippo; Masi, Maurizio

    2016-01-01

    This book offers a state-of-the-art overview of controlled drug delivery systems, covering the most important innovative applications. The principles of controlled drug release and the mechanisms involved in controlled release are clearly explained. The various existing polymeric drug delivery systems are reviewed, and new frontiers in material design are examined in detail, covering a wide range of polymer modification techniques. The concluding chapter is a case study focusing on use of a drug-eluting stent. The book is designed to provide the reader with a complete understanding of the mechanisms and design of controlled drug delivery systems, and to this end includes numerous step-by-step tutorials. It illustrates how chemical engineers can advance medical care by designing polymeric delivery systems that achieve either temporal or spatial control of drug delivery and thus ensure more effective therapy that eliminates the potential for both under-and overdosing.

  1. 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.

  2. Development, optimization and evaluation of polymeric electrospun nanofiber: A tool for local delivery of fluconazole for management of vaginal candidiasis.

    Science.gov (United States)

    Sharma, Rahul; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    The present study is designed to explore the localized delivery of fluconazole using mucoadhesive polymeric nanofibers. Drug-loaded polymeric nanofibers were fabricated by the electrospinning method using polyvinyl alcohol (PVA) as the polymeric constituent. The prepared nanofibers were found to be uniform, non-beaded and non-woven, with the diameter of the fibers ranging from 150 to 180 nm. Further drug release studies indicate a sustained release of fluconazole over a period of 6 h. The results of studies on anti-microbial activity indicated that drug-loaded polymeric nanofibers exhibit superior anti-microbial activity against Candida albicans, when compared to the plain drug.

  3. Emerging Frontiers in Drug Delivery.

    Science.gov (United States)

    Tibbitt, Mark W; Dahlman, James E; Langer, Robert

    2016-01-27

    Medicine relies on the use of pharmacologically active agents (drugs) to manage and treat disease. However, drugs are not inherently effective; the benefit of a drug is directly related to the manner by which it is administered or delivered. Drug delivery can affect drug pharmacokinetics, absorption, distribution, metabolism, duration of therapeutic effect, excretion, and toxicity. As new therapeutics (e.g., biologics) are being developed, there is an accompanying need for improved chemistries and materials to deliver them to the target site in the body, at a therapeutic concentration, and for the required period of time. In this Perspective, we provide an historical overview of drug delivery and controlled release followed by highlights of four emerging areas in the field of drug delivery: systemic RNA delivery, drug delivery for localized therapy, oral drug delivery systems, and biologic drug delivery systems. In each case, we present the barriers to effective drug delivery as well as chemical and materials advances that are enabling the field to overcome these hurdles for clinical impact.

  4. 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.

  5. Design and construction of polymerized-chitosan coated Fe{sub 3}O{sub 4} magnetic nanoparticles and its application for hydrophobic drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Yongling [Key Laboratory for Liquid–solid Structural Evolution and Processing of Materials (Ministry of Education), Engineering Ceramics Key Laboratory of Shandong Province, Shandong University, Jinan 250061 (China); School of Materials Science and Engineering, University of Jinan, Jinan 250022 (China); Shen, Shirley Z. [Materials Science and Engineering, CSIRO, Highett Vic 3190 (Australia); Sun, Huadong [College of Chemical Engineering, China University of Petroleum, Qing Dao 266555 (China); Sun, Kangning, E-mail: sunkangning@sdu.edu.cn [Key Laboratory for Liquid–solid Structural Evolution and Processing of Materials (Ministry of Education), Engineering Ceramics Key Laboratory of Shandong Province, Shandong University, Jinan 250061 (China); School of Materials Science and Engineering, University of Jinan, Jinan 250022 (China); Liu, Futian, E-mail: mse_liuft@ujn.edu.cn [Key Laboratory for Liquid–solid Structural Evolution and Processing of Materials (Ministry of Education), Engineering Ceramics Key Laboratory of Shandong Province, Shandong University, Jinan 250061 (China); School of Materials Science and Engineering, University of Jinan, Jinan 250022 (China); Qi, Yushi; Yan, Jun [School of Materials Science and Engineering, University of Jinan, Jinan 250022 (China)

    2015-03-01

    In this study, a novel hydrogel, chitosan (CS) crosslinked carboxymethyl-β-cyclodextrin (CM-β-CD) polymer modified Fe{sub 3}O{sub 4} magnetic nanoparticles was synthesized for delivering hydrophobic anticancer drug 5-fluorouracil (CS-CDpoly-MNPs). Carboxymethyl-β-cyclodextrin being grafted on the Fe{sub 3}O{sub 4} nanoparticles (CDpoly-MNPs) contributed to an enhancement of adsorption capacities because of the inclusion abilities of its hydrophobic cavity with insoluble anticancer drugs through host–guest interactions. Experimental results indicated that the amounts of crosslinking agent and bonding times played a crucial role in determining morphology features of the hybrid nanocarriers. The nanocarriers exhibited a high loading efficiency (44.7 ± 1.8%) with a high saturation magnetization of 43.8 emu/g. UV–Vis spectroscopy results showed that anticancer drug 5-fluorouracil (5-Fu) could be successfully included into the cavities of the covalently linked CDpoly-MNPs. Moreover, the free carboxymethyl groups could enhance the bonding interactions between the covalently linked CDpoly-MNPs and anticancer drugs. In vitro release studies revealed that the release behaviors of CS-CDpoly-MNPs carriers were pH dependent and demonstrated a swelling and diffusion controlled release. A lower pH value led to swelling effect and electrostatic repulsion contributing to the protonation amine impact of NH{sub 3}{sup +}, and thus resulted in a higher release rate of 5-Fu. The mechanism of 5-Fu encapsulated into the magnetic chitosan nanoparticles was tentatively proposed. - Graphical abstract: A novel nanocarrier, chitosan-coated magnetic drug carrier nanoparticle (CS-CDpoly-MNPs) is fabricated for the delivery of insoluble anticancer drug by grafting CM-β-CD onto the magnetite surface. The grafting of CM-dextrins onto the surface of Fe{sub 3}O{sub 4} nanocrystal clusters can markedly increase the loading capacity of 5-Fu by virtue of CM-dextrins/5-Fu inclusion complex

  6. Asymmetrical Polymer Vesicles for Drug delivery and Other Applications

    Directory of Open Access Journals (Sweden)

    Yi Zhao

    2017-06-01

    Full Text Available Scientists have been attracted by polymersomes as versatile drug delivery systems since the last two decades. Polymersomes have the potential to be versatile drug delivery systems because of their tunable membrane formulations, stabilities in vivo, various physicochemical properties, controlled release mechanisms, targeting abilities, and capacities to encapsulate a wide range of drugs and other molecules. Asymmetrical polymersomes are nano- to micro-sized polymeric capsules with asymmetrical membranes, which means, they have different outer and inner coronas so that they can exhibit better endocytosis rate and endosomal escape ability than other polymeric systems with symmetrical membranes. Hence, asymmetrical polymersomes are highly promising as self-assembled nano-delivery systems in the future for in vivo therapeutics delivery and diagnostic imaging applications. In this review, we prepared a summary about recent research progresses of asymmetrical polymersomes in the following aspects: synthesis, preparation, applications in drug delivery and others.

  7. Acetal-Linked Paclitaxel Polymeric Prodrug Based on Functionalized mPEG-PCL Diblock Polymer for pH-Triggered Drug Delivery

    Directory of Open Access Journals (Sweden)

    Yinglei Zhai

    2017-12-01

    Full Text Available The differences in micro-environment between cancer cells and the normal ones offer the possibility to develop stimuli-responsive drug-delivery systems for overcoming the drawbacks in the clinical use of anticancer drugs, such as paclitaxel, doxorubicin, and etc. Hence, we developed a novel endosomal pH-sensitive paclitaxel (PTX prodrug micelles based on functionalized poly(ethylene glycol-poly(ε-caprolactone (mPEG-PCL diblock polymer with an acid-cleavable acetal (Ace linkage (mPEG-PCL-Ace-PTX. The mPEG-PCL-Ace-PTX5 with a high drug content of 23.5 wt % was self-assembled in phosphate buffer (pH 7.4, 10 mM into nanosized micelles with an average diameter of 68.5 nm. The in vitro release studies demonstrated that mPEG-PCL-Ace-PTX5 micelles was highly pH-sensitive, in which 16.8%, 32.8%, and 48.2% of parent free PTX was released from mPEG-PCL-Ace-PTX5 micelles in 48 h at pH 7.4, 6.0, and 5.0, respectively. Thiazolyl Blue Tetrazolium Bromide (MTT assays suggested that the pH-sensitive PTX prodrug micelles displayed higher therapeutic efficacy against MCF-7 cells compared with free PTX. Therefore, the PTX prodrug micelles with acetal bond may offer a promising strategy for cancer therapy.

  8. Self-Assembled Hydrogel Nanoparticles for Drug Delivery Applications

    Directory of Open Access Journals (Sweden)

    Miguel Gama

    2010-02-01

    Full Text Available Hydrogel nanoparticles—also referred to as polymeric nanogels or macromolecular micelles—are emerging as promising drug carriers for therapeutic applications. These nanostructures hold versatility and properties suitable for the delivery of bioactive molecules, namely of biopharmaceuticals. This article reviews the latest developments in the use of self-assembled polymeric nanogels for drug delivery applications, including small molecular weight drugs, proteins, peptides, oligosaccharides, vaccines and nucleic acids. The materials and techniques used in the development of self-assembling nanogels are also described.

  9. Ceramic drug-delivery devices.

    Science.gov (United States)

    Lasserre, A; Bajpai, P K

    1998-01-01

    A variety of ceramics and delivery systems have been used to deliver chemicals, biologicals, and drugs at various rates for desired periods of time from different sites of implantation. In vitro and in vivo studies have shown that ceramics can successfully be used as drug-delivery devices. Matrices, inserts, reservoirs, cements, and particles have been used to deliver a large variety of therapeutic agents such as antibiotics, anticancer drugs, anticoagulants, analgesics, growth factors, hormones, steroids, and vaccines. In this article, the advantages and disadvantages of conventional drug-delivery systems and the different approaches used to deliver chemical and biological agents by means of ceramic systems will be reviewed.

  10. Amphiphilic block copolymers for drug delivery.

    Science.gov (United States)

    Adams, Monica L; Lavasanifar, Afsaneh; Kwon, Glen S

    2003-07-01

    Amphiphilic block copolymers (ABCs) have been used extensively in pharmaceutical applications ranging from sustained-release technologies to gene delivery. The utility of ABCs for delivery of therapeutic agents results from their unique chemical composition, which is characterized by a hydrophilic block that is chemically tethered to a hydrophobic block. In aqueous solution, polymeric micelles are formed via the association of ABCs into nanoscopic core/shell structures at or above the critical micelle concentration. Upon micellization, the hydrophobic core regions serve as reservoirs for hydrophobic drugs, which may be loaded by chemical, physical, or electrostatic means, depending on the specific functionalities of the core-forming block and the solubilizate. Although the Pluronics, composed of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide), are the most widely studied ABC system, copolymers containing poly(L-amino acid) and poly(ester) hydrophobic blocks have also shown great promise in delivery applications. Because each ABC has unique advantages with respect to drug delivery, it may be possible to choose appropriate block copolymers for specific purposes, such as prolonging circulation time, introduction of targeting moieties, and modification of the drug-release profile. ABCs have been used for numerous pharmaceutical applications including drug solubilization/stabilization, alteration of the pharmacokinetic profile of encapsulated substances, and suppression of multidrug resistance. The purpose of this minireview is to provide a concise, yet detailed, introduction to the use of ABCs and polymeric micelles as delivery agents as well as to highlight current and past work in this area. Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association

  11. Macrophage specific drug delivery in experimental leishmaniasis.

    Science.gov (United States)

    Basu, Mukul Kumar; Lala, Sanchaita

    2004-09-01

    Macrophage-specific delivery systems are the subject of much interest nowadays, because of the fact that macrophages act as host cells for many parasites and bacteria, which give rise to outbreak of so many deadly diseases(eg. leishmaniasis, tuberculosis etc.) in humans. To combat these deadly diseases initially macrophage specific liposomal delivery system were thought of and tested in vivo against experimental leishmaniasis in hamsters using a series of indigenous or synthetic antileishmanial compounds and the results were critically discussed. In vitro testing was also done against macrophages infected with Leishmania donovani, the causative agent for visceral leishmaniasis. The common problem of liposome therapy being their larger size, stability and storage, non-ionic surfactant vesicles, niosomes were prepared, for their different drug distribution and release characteristics compared to liposomes. When tested in vivo, the retention capacity of niosomes was found to be higher than that of liposomes due to the absence of lipid molecules and their smaller size. Thus the therapeutic efficacy of certain antileishmanial compounds was found to be better than that in the liposomal form. The niosomes, being cheaper, less toxic, biodegradable and non-immunogenic, were considered for sometime as suitable alternatives to liposomes as drug carriers. Besides the advent of other classical drugs carriers(e.g. neoglycoproteins), the biggest challenge came from polymeric delivery vehicles, specially the polymeric nanoparticles which were made of cost effective biodegradable polymers and different natural polymers. Because of very small size and highly stable nature, use of nanoparticles as effective drug carriers has been explored in experimental leishmaniasis using a series of antileishmanial compounds, both of indigenous and synthetic origin. The feasibility of application in vivo, when tested for biological as well as for other physicochemical parameters, the polymeric

  12. Providing an address for delivery of nanoencapsulated TB drugs

    CSIR Research Space (South Africa)

    Lemmer, Yolandy

    2010-06-01

    Full Text Available compliance and drug resistance pose a great challenge to TB treatment programs worldwide. To improve the current inadequate therapeutic management of TB, a polymeric anti-TB nanodrug delivery system, for anti-TB drugs, was developed that could enable entry...

  13. Organoclays for drug delivery Systems

    OpenAIRE

    Canovas Creus, Alba

    2008-01-01

    Modified clays can be used as carriers of drugs due to their suitable properties and structure in order to achieve improvements in drug delivery. The study of this thesis starts with an introduction to mineral clays and its classification, properties and characterization, then deepens into modified clays (properties, comparison with mineral clays, applications and procedure of modification). Another chapter is focused in drug delivery: definition, its difficulties nowadays and the different w...

  14. Bioresponsive matrices in drug delivery

    Directory of Open Access Journals (Sweden)

    Ye George JC

    2010-11-01

    Full Text Available Abstract For years, the field of drug delivery has focused on (1 controlling the release of a therapeutic and (2 targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli.

  15. Drug delivery across length scales.

    Science.gov (United States)

    Delcassian, Derfogail; Patel, Asha K; Cortinas, Abel B; Langer, Robert

    2018-02-20

    Over the last century, there has been a dramatic change in the nature of therapeutic, biologically active molecules available to treat disease. Therapies have evolved from extracted natural products towards rationally designed biomolecules, including small molecules, engineered proteins and nucleic acids. The use of potent drugs which target specific organs, cells or biochemical pathways, necessitates new tools which can enable controlled delivery and dosing of these therapeutics to their biological targets. Here, we review the miniaturisation of drug delivery systems from the macro to nano-scale, focussing on controlled dosing and controlled targeting as two key parameters in drug delivery device design. We describe how the miniaturisation of these devices enables the move from repeated, systemic dosing, to on-demand, targeted delivery of therapeutic drugs and highlight areas of focus for the future.

  16. Oral delivery of anticancer drugs

    DEFF Research Database (Denmark)

    Thanki, Kaushik; Gangwal, Rahul P; Sangamwar, Abhay T

    2013-01-01

    The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes improvement in quality of life of patients and reduced health care costs. Subsequently, the challenges...... incurred in the oral delivery of anticancer agents have been especially emphasized. Sincere efforts have been made to compile the various physicochemical properties of anticancer drugs from either literature or predicted in silico via GastroPlus™. The later section of the paper reviews various emerging...... trends to tackle the challenges associated with oral delivery of anticancer drugs. These invariably include efflux transporter based-, functional excipient- and nanocarrier based-approaches. The role of drug nanocrystals and various others such as polymer based- and lipid based...

  17. Polymeric Micelles as Novel Carriers for Poorly Soluble Drugs--A Review.

    Science.gov (United States)

    Reddy, B Pavan Kumar; Yadav, Hemant K S; Nagesha, Dattatri K; Raizaday, Abhay; Karim, Abdul

    2015-06-01

    Polymeric micelles are used as 'smart drug carriers' for targeting certain areas of the body by making them stimuli-sensitive or by attachment of a specific ligand molecule onto their surface. The main aim of using polymeric micelles is to deliver the poorly water soluble drugs. Now-a-days they are used especially in the areas of cancer therapy also. In this article we have reviewed several aspects of polymeric micelles concerning their mechanism of formation, chemical nature, preparation and characterization techniques, and their applications in the areas of drug delivery.

  18. Microwave Assisted Drug Delivery

    DEFF Research Database (Denmark)

    Jónasson, Sævar Þór; Zhurbenko, Vitaliy; Johansen, Tom Keinicke

    2014-01-01

    In this work, the microwave radiation is adopted for remote activation of pharmaceutical drug capsules inside the human body in order to release drugs at a pre-determined time and location. An array of controllable transmitting sources is used to produce a constructive interference at a certain...... focus point inside the body, where the drugs are then released from the specially designed capsules. An experimental setup for microwave activation has been developed and tested on a body phantom that emulates the human torso. A design of sensitive receiving structures for integration with a drug...

  19. Biomaterials for drug delivery patches.

    Science.gov (United States)

    Santos, Lúcia F; Correia, Ilídio J; Silva, A Sofia; Mano, João F

    2018-06-15

    The limited efficiency of conventional drugs has been instigated the development of new and more effective drug delivery systems (DDS). Transdermal DDS, are associated with numerous advantages such its painless application and less frequent replacement and greater flexibility of dosing, features that triggered the research and development of such devices. Such systems have been produced using either biopolymer; or synthetic polymers. Although the first ones are safer, biocompatible and present a controlled degradation by human enzymes or water, the second ones are the most currently available in the market due to their greater mechanical resistance and flexibility, and non-degradation over time. This review highlights the most recent advances (mainly in the last five years) of patches aimed for transdermal drug delivery, focusing on the different materials (natural, synthetic and blends) and latest designs for the development of such devices, emphasizing also their combination with drug carriers that enable enhanced drug solubility and a more controlled release of the drug over the time. The benefits and limitations of different patches formulations are considered with reference to their appliance to transdermal drug delivery. Furthermore, a record of the currently available patches on the market is given, featuring their most relevant characteristics. Finally, a list of most recent/ongoing clinical trials regarding the use of patches for skin disorders is detailed and critical insights on the current state of patches for transdermal drug delivery are also provided. Copyright © 2018. Published by Elsevier B.V.

  20. Microcontainers for Intestinal Drug Delivery

    DEFF Research Database (Denmark)

    Tentor, Fabio; Mazzoni, Chiara; Keller, Stephan Sylvest

    Among all the drug administration routes, the oral one is the most preferred by the patients being less invasive, faster and easier. Oral drug delivery systems designed to target the intestine are produced by powder technology and capsule formulations. Those systems including micro- and nano...

  1. Albumin-based drug delivery

    DEFF Research Database (Denmark)

    Larsen, Maja Thim; Kuhlmann, Matthias; Hvam, Michael Lykke

    2016-01-01

    The effectiveness of a drug is dependent on accumulation at the site of action at therapeutic levels, however, challenges such as rapid renal clearance, degradation or non-specific accumulation requires drug delivery enabling technologies. Albumin is a natural transport protein with multiple ligand...... binding sites, cellular receptor engagement, and a long circulatory half-life due to interaction with the recycling neonatal Fc receptor. Exploitation of these properties promotes albumin as an attractive candidate for half-life extension and targeted intracellular delivery of drugs attached by covalent...... conjugation, genetic fusions, association or ligand-mediated association. This review will give an overview of albumin-based products with focus on the natural biological properties and molecular interactions that can be harnessed for the design of a next-generation drug delivery platform....

  2. Polymer architecture and drug delivery.

    Science.gov (United States)

    Qiu, Li Yan; Bae, You Han

    2006-01-01

    Polymers occupy a major portion of materials used for controlled release formulations and drug-targeting systems because this class of materials presents seemingly endless diversity in topology and chemistry. This is a crucial advantage over other classes of materials to meet the ever-increasing requirements of new designs of drug delivery formulations. The polymer architecture (topology) describes the shape of a single polymer molecule. Every natural, seminatural, and synthetic polymer falls into one of categorized architectures: linear, graft, branched, cross-linked, block, star-shaped, and dendron/dendrimer topology. Although this topic spans a truly broad area in polymer science, this review introduces polymer architectures along with brief synthetic approaches for pharmaceutical scientists who are not familiar with polymer science, summarizes the characteristic properties of each architecture useful for drug delivery applications, and covers recent advances in drug delivery relevant to polymer architecture.

  3. Polymeric Gene Delivery for Diabetic Treatment

    Directory of Open Access Journals (Sweden)

    Sung Wan Kim

    2011-08-01

    Full Text Available Several polymers were used to delivery genes to diabetic animals. Polyaminobutyl glycolic acid was utilized to deliver IL-10 plasmid DNA to prevent autoimmune insulitis of non-obese diabetic (NOD mouse. Polyethylene glycol grafted polylysine was combined with antisense glutamic acid decarboxylase (GAD MRNA to represent GAD autoantigene expression. GLP1 and TSTA (SP-EX4 were delivered by bioreducible polymer to stop diabetic progression. Fas siRNA delivery was carried out to treat diabetic NOD mice animal.

  4. Biodegradable polymers for targeted delivery of anti-cancer drugs.

    Science.gov (United States)

    Doppalapudi, Sindhu; Jain, Anjali; Domb, Abraham J; Khan, Wahid

    2016-06-01

    Biodegradable polymers have been used for more than three decades in cancer treatment and have received increased interest in recent years. A range of biodegradable polymeric drug delivery systems designed for localized and systemic administration of therapeutic agents as well as tumor-targeting macromolecules has entered into the clinical phase of development, indicating the significance of biodegradable polymers in cancer therapy. This review elaborates upon applications of biodegradable polymers in the delivery and targeting of anti-cancer agents. Design of various drug delivery systems based on biodegradable polymers has been described. Moreover, the indication of polymers in the targeted delivery of chemotherapeutic drugs via passive, active targeting, and localized drug delivery are also covered. Biodegradable polymer-based drug delivery systems have the potential to deliver the payload to the target and can enhance drug availability at desired sites. Systemic toxicity and serious side effects observed with conventional cancer therapeutics can be significantly reduced with targeted polymeric systems. Still, there are many challenges that need to be met with respect to the degradation kinetics of the system, diffusion of drug payload within solid tumors, targeting tumoral tissue and tumor heterogeneity.

  5. Polymer nanogels: a versatile nanoscopic drug delivery platform

    Science.gov (United States)

    Chacko, Reuben T.; Ventura, Judy; Zhuang, Jiaming; Thayumanavan, S.

    2012-01-01

    In this review we put the spotlight on crosslinked polymer nanogels, a promising platform that has the characteristics of an “ideal” drug delivery vehicle. Some of the key aspects of drug delivery vehicle design like stability, response to biologically relevant stimuli, passive targeting, active targeting, toxicity and ease of synthesis are discussed. We discuss several delivery systems in this light and highlight some examples of systems, which satisfy some or all of these design requirements. In particular, we point to the advantages that crosslinked polymeric systems bring to drug delivery. We review some of the synthetic methods of nanogel synthesis and conclude with the diverse applications in drug delivery where nanogels have been fruitfully employed. PMID:22342438

  6. Advances in buccal drug delivery.

    Science.gov (United States)

    Birudaraj, Raj; Mahalingam, Ravichandran; Li, Xiaoling; Jasti, Bhaskara R

    2005-01-01

    The buccal route offers an attractive alternative for systemic drug delivery of drugs because of better patient compliance, ease of dosage form removal in emergencies, robustness, and good accessibility. Use of buccal mucosa for drug absorption was first attempted by Sobrero in 1847, and since then much research was done to deliver drugs through this route. Today, research is more focused on the development of suitable delivery devices, permeation enhancement, and buccal delivery of drugs that undergo a first-pass effect, such as cardiovascular drugs, analgesics, and peptides. In addition, studies have been conducted on the development of controlled or slow release delivery systems for systemic and local therapy of diseases in the oral cavity. In this review, the anatomy and physiology of buccal mucosa, followed by discussion of recent literature on the buccal permeation enhancement, and pathways of enhancement for various molecules are detailed. In addition, bioadhesion theories from historic perspective and current status are discussed. The various dosage forms on the market and in different stages of development are also reviewed.

  7. Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

    Directory of Open Access Journals (Sweden)

    Priya Bawa

    2011-12-01

    Full Text Available Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.

  8. pH-sensitive polymeric cisplatin-ion complex with styrene-maleic acid copolymer exhibits tumor-selective drug delivery and antitumor activity as a result of the enhanced permeability and retention effect.

    Science.gov (United States)

    Saisyo, Atsuyuki; Nakamura, Hideaki; Fang, Jun; Tsukigawa, Kenji; Greish, Khaled; Furukawa, Hiroyuki; Maeda, Hiroshi

    2016-02-01

    Cisplatin (CDDP) is widely used to treat various cancers. However, its distribution to normal tissues causes serious adverse effects. For this study, we synthesized a complex of styrene-maleic acid copolymer (SMA) and CDDP (SMA-CDDP), which formed polymeric micelles, to achieve tumor-selective drug delivery based on the enhanced permeability and retention (EPR) effect. SMA-CDDP is obtained by regulating the pH of the reaction solution of SMA and CDDP. The mean SMA-CDDP particle size was 102.5 nm in PBS according to electrophoretic light scattering, and the CDDP content was 20.1% (w/w). The release rate of free CDDP derivatives from the SMA-CDDP complex at physiological pH was quite slow (0.75%/day), whereas it was much faster at pH 5.5 (4.4%/day). SMA-CDDP thus had weaker in vitro toxicity at pH 7.4 but higher cytotoxicity at pH 5.5. In vivo pharmacokinetic studies showed a 5-fold higher tumor concentration of SMA-CDDP than of free CDDP. SMA-CDDP had more effective antitumor potential but lower toxicity than did free CDDP in mice after i.v. administration. Administration of parental free CDDP at 4 mg/kg×3 caused a weight loss of more than 5%; SMA-CDDP at 60 mg/kg (CDDP equivalent)×3 caused no significant weight change but markedly suppressed S-180 tumor growth. These findings together suggested using micelles of the SMA-CDDP complex as a cancer chemotherapeutic agent because of beneficial properties-tumor-selective accumulation and relatively rapid drug release at the acidic pH of the tumor-which resulted in superior antitumor effects and fewer side effects compared with free CDDP. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Nanostructures for protein drug delivery.

    Science.gov (United States)

    Pachioni-Vasconcelos, Juliana de Almeida; Lopes, André Moreni; Apolinário, Alexsandra Conceição; Valenzuela-Oses, Johanna Karina; Costa, Juliana Souza Ribeiro; Nascimento, Laura de Oliveira; Pessoa, Adalberto; Barbosa, Leandro Ramos Souza; Rangel-Yagui, Carlota de Oliveira

    2016-02-01

    Use of nanoscale devices as carriers for drugs and imaging agents has been extensively investigated and successful examples can already be found in therapy. In parallel, recombinant DNA technology together with molecular biology has opened up numerous possibilities for the large-scale production of many proteins of pharmaceutical interest, reflecting in the exponentially growing number of drugs of biotechnological origin. When we consider protein drugs, however, there are specific criteria to take into account to select adequate nanostructured systems as drug carriers. In this review, we highlight the main features, advantages, drawbacks and recent developments of nanostructures for protein encapsulation, such as nanoemulsions, liposomes, polymersomes, single-protein nanocapsules and hydrogel nanoparticles. We also discuss the importance of nanoparticle stabilization, as well as future opportunities and challenges in nanostructures for protein drug delivery.

  10. 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.

  11. Advanced drug and gene delivery systems based on functional biodegradable polycarbonates and copolymers

    NARCIS (Netherlands)

    Chen, Wei; Meng, Fenghua; Cheng, R.; Deng, C.; Feijen, Jan; Zhong, Zhiyuan

    2014-01-01

    Biodegradable polymeric nanocarriers are one of the most promising systems for targeted and controlled drug and gene delivery. They have shown several unique advantages such as excellent biocompatibility, prolonged circulation time, passive tumor targeting via the enhanced permeability and retention

  12. Clinical developments of chemotherapeutic nanomedicines: Polymers and liposomes for delivery of camptothecins and platinum (II) drugs

    KAUST Repository

    Kieler-Ferguson, Heidi M.; Frechet, Jean; Szoka, Francis C.

    2013-01-01

    For the past 40 years, liposomal and polymeric delivery vehicles have been studied as systems capable of modulating the cytotoxicity of small molecule chemotherapeutics, increasing tumor bearing animal survival times, and improving drug targeting

  13. Novel Polymeric Prodrugs of Valproic Acid as Anti- Epilepsy Drugs ...

    African Journals Online (AJOL)

    Epilepsy Drugs: Synthesis, Characterization and In-vitro ... The release of VPA from polymeric prodrugs was studied using cellophane ... pharmacokinetics and accessibility in market [8]. ..... between the drug and polymer chain can affect.

  14. Molecularly Imprinted Polymers: Novel Discovery for Drug Delivery.

    Science.gov (United States)

    Dhanashree, Surve; Priyanka, Mohite; Manisha, Karpe; Vilasrao, Kadam

    2016-01-01

    Molecularly imprinted polymers (MIP) are novel carriers synthesized by imprinting of a template over a polymer. This paper presents the recent application of MIP for diagnostic and therapeutic drug delivery. MIP owing to their 3D polymeric structures and due to bond formation with the template serves as a reservoir of active causing stimuli sensitive, enantioselective, targetted and/or controlled release. The review elaborates about key factors for optimization of MIP, controlled release by MIP for various administration routes various forms like patches, contact lenses, nanowires along with illustrations. To overcome the limitation of organic solvent usage causing increased cost, water compatible MIP and use of supercritical fluid technology for molecular imprinting were developed. Novel methods for developing water compatible MIP like pickering emulsion polymerization, co-precipitation method, cyclodextrin imprinting, surface grafting, controlled/living radical chain polymerization methods are described with illustration in this review. Various protein imprinting methods like bulk, epitope and surface imprinting are described along with illustrations. Further, application of MIP in microdevices as biomimetic sensing element for personalized therapy is elaborated. Although development and application of MIP in drug delivery is still at its infancy, constant efforts of researchers will lead to a novel intelligent drug delivery with commercial value. Efforts should be directed in developing solid oral dosage forms consisting of MIP for therapeutic protein and peptide delivery and targeted release of potent drugs addressing life threatening disease like cancer. Amalgamation of bio-engineering and pharmaceutical techniques can make these future prospects into reality.

  15. Ultrasound mediated nanoparticle drug delivery

    Science.gov (United States)

    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

  16. Food, physiology and drug delivery.

    Science.gov (United States)

    Varum, F J O; Hatton, G B; Basit, A W

    2013-12-05

    Gastrointestinal physiology is dynamic and complex at the best of times, and a multitude of known variables can affect the overall bioavailability of drugs delivered via the oral route. Yet while the influences of food and beverage intake as just two of these variables on oral drug delivery have been extensively documented in the wider literature, specific information on their effects remains sporadic, and is not so much contextually reviewed. Food co-ingestion with oral dosage forms can mediate several changes to drug bioavailability, yet the precise mechanisms underlying this have yet to be fully elucidated. Likewise, the often detrimental effects of alcohol (ethanol) on dosage form performance have been widely observed experimentally, but knowledge of which has only moderately impacted on clinical practice. Here, we attempt to piece together the available subject matter relating to the influences of both solid and liquid foodstuffs on the gastrointestinal milieu and the implications for oral drug delivery, with particular emphasis on the behaviour of modified-release dosage forms, formulation robustness and drug absorption. Providing better insight into these influences, and exemplifying cases where formulations have been developed or modified to circumvent their associated problems, can help to appropriately direct the design of future in vitro digestive modelling systems as well as oral dosage forms resilient to these effects. Moreover, this will help to better our understanding of the impact of food and alcohol intake on normal gut behaviour and function. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Drug delivery device including electrolytic pump

    KAUST Repository

    Foulds, Ian G.; Buttner, Ulrich; Yi, Ying

    2016-01-01

    Systems and methods are provided for a drug delivery device and use of the device for drug delivery. In various aspects, the drug delivery device combines a “solid drug in reservoir” (SDR) system with an electrolytic pump. In various aspects an improved electrolytic pump is provided including, in particular, an improved electrolytic pump for use with a drug delivery device, for example an implantable drug delivery device. A catalytic reformer can be incorporated in a periodically pulsed electrolytic pump to provide stable pumping performance and reduced actuation cycle.

  18. Drug delivery device including electrolytic pump

    KAUST Repository

    Foulds, Ian G.

    2016-03-31

    Systems and methods are provided for a drug delivery device and use of the device for drug delivery. In various aspects, the drug delivery device combines a “solid drug in reservoir” (SDR) system with an electrolytic pump. In various aspects an improved electrolytic pump is provided including, in particular, an improved electrolytic pump for use with a drug delivery device, for example an implantable drug delivery device. A catalytic reformer can be incorporated in a periodically pulsed electrolytic pump to provide stable pumping performance and reduced actuation cycle.

  19. 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.

  20. Buccal mucosa as a route for systemic drug delivery: a review.

    Science.gov (United States)

    Shojaei, A H

    1998-01-01

    Within the oral mucosal cavity, the buccal region offers an attractive route of administration for systemic drug delivery. The mucosa has a rich blood supply and it is relatively permeable. It is the objective of this article to review buccal drug delivery by discussing the structure and environment of the oral mucosa and the experimental methods used in assessing buccal drug permeation/absorption. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based delivery systems

  1. Ionic liquids in drug delivery.

    Science.gov (United States)

    Shamshina, Julia L; Barber, Patrick S; Rogers, Robin D

    2013-10-01

    To overcome potential problems with solid-state APIs, such as polymorphism, solubility and bioavailability, pure liquid salt (ionic liquid) forms of active pharmaceutical ingredients (API-ILs) are considered here as a design strategy. After a critical review of the current literature, the recent development of the API-ILs strategy is presented, with a particular focus on the liquefaction of drugs. A variety of IL tools for control over the liquid salt state of matter are discussed including choice of counterion to produce an IL from a given API; the concept of oligomeric ions that enables liquefaction of solid ILs by changing the stoichiometry or complexity of the ions; formation of 'liquid co-crystals' where hydrogen bonding is the driving force in the liquefaction of a neutral acid-base complex; combining an IL strategy with the prodrug strategy to improve the delivery of solid APIs; using ILs as delivery agents via trapping a drug in a micelle and finally ILs designed with tunable hydrophilic-lipophilic balance that matches the structural requirements needed to solubilize poorly water-soluble APIs. The authors believe that API-IL approaches may save failed lead candidates, extend the patent life of current APIs, lead to new delivery options or even new pharmaceutical action. They encourage the pharmaceutical industry to invest more research into the API-IL platform as it could lead to fast-tracked approval based on similarities to the APIs already approved.

  2. 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.

  3. Recent Advances and Perspectives in Liposomes for Cutaneous Drug Delivery.

    Science.gov (United States)

    Carita, Amanda C; Eloy, Josimar O; Chorilli, Marlus; Lee, Robert J; Leonardi, Gislaine Ricci

    2018-02-13

    The cutaneous route is attractive for the delivery of drugs in the treatment of a wide variety of diseases. However the stratum corneum (SC) is an effective barrier that hampers skin penetration. Within this context, liposomes emerge as a potential carrier for improving topical delivery of therapeutic agents. In this review, we aimed to discuss key aspects for the topical delivery by drug-loaded liposomes. Phospholipid type and phase transition temperature have been shown to affect liposomal topical delivery. The effect of surface charge is subject to considerable variation depending on drug and composition. In addition, modified vesicles with the presence of components for permeation enhancement, such as surfactants and solvents, have been shown to have a considerable effect. These liposomes include: Transfersomes, Niosomes, Ethosomes, Transethosomes, Invasomes, coated liposomes, penetration enhancer containing vesicles (PEVs), fatty acids vesicles, Archaeosomes and Marinosomes. Furthermore, adding polymeric coating onto liposome surface could influence cutaneous delivery. Mechanisms of delivery include intact vesicular skin penetration, free drug diffusion, permeation enhancement, vesicle adsorption to and/or fusion with the SC, trans-appendageal penetration, among others. Finally, several skin conditions, including acne, melasma, skin aging, fungal infections and skin cancer, have benefited from liposomal topical delivery of drugs, with promising in vitro and in vivo results. However, despite the existence of some clinical trials, more studies are needed to be conducted in order to explore the potential of liposomes in the dermatological field. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Ultrasound-guided drug delivery in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chowdhury, Sayan Mullick; Lee, Tae Hwa; Willmann, Jugen K. [Dept. of Radiology, Stanford University School of Medicine, Stanford (United States)

    2017-07-15

    Recent advancements in ultrasound and microbubble (USMB) mediated drug delivery technology has shown that this approach can improve spatially confined delivery of drugs and genes to target tissues while reducing systemic dose and toxicity. The mechanism behind enhanced delivery of therapeutics is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. In this review, progress and challenges of USMB mediated drug delivery are summarized, with special focus on cancer therapy.

  5. Ultrasound-guided drug delivery in cancer

    Directory of Open Access Journals (Sweden)

    Sayan Mullick Chowdhury

    2017-07-01

    Full Text Available Recent advancements in ultrasound and microbubble (USMB mediated drug delivery technology has shown that this approach can improve spatially confined delivery of drugs and genes to target tissues while reducing systemic dose and toxicity. The mechanism behind enhanced delivery of therapeutics is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. In this review, progress and challenges of USMB mediated drug delivery are summarized, with special focus on cancer therapy.

  6. Polymeric drugs: Advances in the development of pharmacologically active polymers

    Science.gov (United States)

    Li, Jing; Yu, Fei; Chen, Yi; Oupický, David

    2015-01-01

    Synthetic polymers play a critical role in pharmaceutical discovery and development. Current research and applications of pharmaceutical polymers are mainly focused on their functions as excipients and inert carriers of other pharmacologically active agents. This review article surveys recent advances in alternative pharmaceutical use of polymers as pharmacologically active agents known as polymeric drugs. Emphasis is placed on the benefits of polymeric drugs that are associated with their macromolecular character and their ability to explore biologically relevant multivalency processes. We discuss the main therapeutic uses of polymeric drugs as sequestrants, antimicrobials, antivirals, and anticancer and anti-inflammatory agents. PMID:26410809

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Critical Assessment of Implantable Drug Delivery Devices in Glaucoma Management

    Directory of Open Access Journals (Sweden)

    Dharani Manickavasagam

    2013-01-01

    Full Text Available Glaucoma is a group of heterogeneous disorders involving progressive optic neuropathy that can culminate into visual impairment and irreversible blindness. Effective therapeutic interventions must address underlying vulnerability of retinal ganglion cells (RGCs to degeneration in conjunction with correcting other associated risk factors (such as elevated intraocular pressure. However, realization of therapeutic outcomes is heavily dependent on suitable delivery system that can overcome myriads of anatomical and physiological barriers to intraocular drug delivery. Development of clinically viable sustained release systems in glaucoma is a widely recognized unmet need. In this regard, implantable delivery systems may relieve the burden of chronic drug administration while potentially ensuring high intraocular drug bioavailability. Presently there are no FDA-approved implantable drug delivery devices for glaucoma even though there are several ongoing clinical studies. The paper critically assessed the prospects of polymeric implantable delivery systems in glaucoma while identifying factors that can dictate (a patient tolerability and acceptance, (b drug stability and drug release profiles, (c therapeutic efficacy, and (d toxicity and biocompatibility. The information gathered could be useful in future research and development efforts on implantable delivery systems in glaucoma.

  9. Microspheres and Nanotechnology for Drug Delivery.

    Science.gov (United States)

    Jóhannesson, Gauti; Stefánsson, Einar; Loftsson, Thorsteinn

    2016-01-01

    Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye. © 2016 S. Karger AG, Basel.

  10. PREPARATION AND CHARACTERIZATION OF CHITOSAN TABLETS OF ACECLOFENAC FOR COLON TARGETED DRUG DELIVERY

    OpenAIRE

    UMA DEVI,THIRUGANESH, SURESH

    2013-01-01

    The present study objective was to develop novel colon specific drug delivery systems for aceclofenac using chitosan as a microbially degradable polymeric carrier and to coat the optimized batches with a pH dependent polymeric coating solution containing Eudragit L 100 and S 100 (1:4). Tablets containing four proportions of chitosan were prepared. The tablets were evaluated for physicochemical properties, drug content, dissolution, water uptake & erosion characteristics, in vitro drug rel...

  11. Nanostructured materials for selective recognition and targeted drug delivery

    International Nuclear Information System (INIS)

    Kotrotsiou, O; Kotti, K; Dini, E; Kammona, O; Kiparissides, C

    2005-01-01

    Selective recognition requires the introduction of a molecular memory into a polymer matrix in order to make it capable of rebinding an analyte with a very high specificity. In addition, targeted drug delivery requires drug-loaded vesicles which preferentially localize to the sites of injury and avoid uptake into uninvolved tissues. The rapid evolution of nanotechnology is aiming to fulfill the goal of selective recognition and optimal drug delivery through the development of molecularly imprinted polymeric (MIP) nanoparticles, tailor-made for a diverse range of analytes (e.g., pharmaceuticals, pesticides, amino acids, etc.) and of nanostructured targeted drug carriers (e.g., liposomes and micelles) with increased circulation lifetimes. In the present study, PLGA microparticles containing multilamellar vesicles (MLVs), and MIP nanoparticles were synthesized to be employed as drug carriers and synthetic receptors respectively

  12. Polymeric micelles as a drug carrier for tumor targeting

    Directory of Open Access Journals (Sweden)

    Neha M Dand

    2013-01-01

    Full Text Available Polymeric micelle can be targeted to tumor site by passive and active mechanism. Some inherent properties of polymeric micelle such as size in nanorange, stability in plasma, longevity in vivo, and pathological characteristics of tumor make polymeric micelles to be targeted at the tumor site by passive mechanism called enhanced permeability and retention effect. Polymeric micelle formed from the amphiphilic block copolymer is suitable for encapsulation of poorly water soluble, hydrophobic anticancer drugs. Other characteristics of polymeric micelles such as separated functionality at the outer shell are useful for targeting the anticancer drug to tumor by active mechanisms. Polymeric micelles can be conjugated with many ligands such as antibodies fragments, epidermal growth factors, α2 -glycoprotein, transferrine, and folate to target micelles to cancer cells. Application of heat and ultrasound are the alternative methods to enhance drug accumulation in tumoral cells. Targeting using micelles can also be done to tumor angiogenesis which is the potentially promising target for anticancer drugs. This review summarizes about recently available information regarding targeting the anticancer drug to the tumor site using polymeric micelles.

  13. Buccoadhesive drug delivery systems--extensive review on recent patents.

    Science.gov (United States)

    Pathan, Shadab A; Iqbal, Zeenat; Sahani, Jasjeet K; Talegaonkar, Sushma; Khar, Roop K; Ahmad, Farhan J

    2008-01-01

    Peroral administration of drugs, although most preferred by both clinicians and patients has several disadvantages such as hepatic first pass metabolism and enzymatic degradation within the GI tract, that prohibit oral administration of certain classes of drugs especially peptides and proteins. Consequently, other absorptive mucosae are considered as potential sites for administration of these drugs. Among the various transmucosal routes studied the buccal mucosa offers several advantages for controlled drug delivery for extended period of time. The mucosa is well supplied with both vascular and lymphatic drainage and first-pass metabolism in the liver and pre-systemic elimination in the gastrointestinal tract is avoided. The area is well suited for a retentive device and appears to be acceptable to the patient. With the right dosage form, design and formulation, the permeability and the local environment of the mucosa can be controlled and manipulated in order to accommodate drug permeation. Buccal drug delivery is thus a promising area for continued research with the aim of systemic and local delivery of orally inefficient drugs as well as feasible and attractive alternative for non-invasive delivery of potent protein and peptide drug molecules. Extensive review pertaining specifically to the patents relating to buccal drug delivery is currently available. However, many patents e.g. US patents 6, 585,997; US20030059376A1 etc. have been mentioned in few articles. It is the objective of this article to extensively review buccal drug delivery by discussing the recent patents available. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based delivery systems.

  14. Self-nanoemulsifying drug delivery systems for oral insulin delivery

    DEFF Research Database (Denmark)

    Li, Ping; Tan, Angel; Prestidge, Clive A

    2014-01-01

    This study aims at evaluating the combination of self-nanoemulsifying drug delivery systems (SNEDDS) and enteric-coated capsules as a potential delivery strategy for oral delivery of insulin. The SNEDDS preconcentrates, loaded with insulin-phospholipid complex at different levels (0, 2.5 and 10% w...

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

    CERN Document Server

    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.

  16. A REVIEW ON OSMOTIC DRUG DELIVERY SYSTEM

    OpenAIRE

    Harnish Patel; Upendra Patel; Hiren Kadikar; Bhavin Bhimani; Dhiren Daslaniya; Ghanshyam Patel

    2012-01-01

    Conventional oral drug delivery systems supply an instantaneous release of drug, which cannot control the release of the drug and effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the process of osmosis. Osmotic devices are the most promising strategy based systems for controlled drug delivery. They are the most reliable con...

  17. Combination Drug Delivery Approaches in Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jun H. Lee

    2012-01-01

    Full Text Available Disseminated metastatic breast cancer needs aggressive treatment due to its reduced response to anticancer treatment and hence low survival and quality of life. Although in theory a combination drug therapy has advantages over single-agent therapy, no appreciable survival enhancement is generally reported whereas increased toxicity is frequently seen in combination treatment especially in chemotherapy. Currently used combination treatments in metastatic breast cancer will be discussed with their challenges leading to the introduction of novel combination anticancer drug delivery systems that aim to overcome these challenges. Widely studied drug delivery systems such as liposomes, dendrimers, polymeric nanoparticles, and water-soluble polymers can concurrently carry multiple anticancer drugs in one platform. These carriers can provide improved target specificity achieved by passive and/or active targeting mechanisms.

  18. Transdermal drug delivery: approaches and significance

    OpenAIRE

    Murthy, SATHYANARAYANA

    2012-01-01

    S Narasimha MurthyDepartment of Pharmaceutics, The University of Mississippi, USATransdermal drug delivery systems deliver drugs through the skin as an alternative to oral, intravascular, subcutaneous, and transmucosal routes. Potential advantages of transdermal delivery include, but are not limited to, elimination of first-pass metabolism, steady delivery/blood levels, better patient compliance, reduced systemic drug interactions, possible dose intervention, avoidance of medically assisted d...

  19. SMART POLYMERS: INNOVATIONS IN NOVEL DRUG DELIVERY

    OpenAIRE

    Apoorva Mahajan; Geeta Aggarwal

    2011-01-01

    Smart polymers are attracting the researchers for development of novel drug delivery systems. Importance of smart polymers is rising day by day as these polymers undergo large reversible, physical or chemical changes in response to small changes in the environmental conditions such as pH, temperature, dual- stimuli, light and phase transition. Smart polymers are representing promising means for targeted drug delivery, enhanced drug delivery, gene therapy, actuator stimuli and protein folders....

  20. Collagen macromolecular drug delivery systems

    International Nuclear Information System (INIS)

    Gilbert, D.L.

    1988-01-01

    The objective of this study was to examine collagen for use as a macromolecular drug delivery system by determining the mechanism of release through a matrix. Collagen membranes varying in porosity, crosslinking density, structure and crosslinker were fabricated. Collagen characterized by infrared spectroscopy and solution viscosity was determined to be pure and native. The collagen membranes were determined to possess native vs. non-native quaternary structure and porous vs. dense aggregate membranes by electron microscopy. Collagen monolithic devices containing a model macromolecule (inulin) were fabricated. In vitro release rates were found to be linear with respect to t 1/2 and were affected by crosslinking density, crosslinker and structure. The biodegradation of the collagen matrix was also examined. In vivo biocompatibility, degradation and 14 C-inulin release rates were evaluated subcutaneously in rats

  1. Buccal Mucosa as A Route for Systemic Drug Delivery: A Review

    OpenAIRE

    Dhaval A. Pate; M. R. Pate; K. R. Pate; N. M. Pate

    2012-01-01

    Within the oral mucosal cavity, the buccal region offers an attractive route of administration for systemic drug delivery. The mucosa has a rich blood supply and it is relatively permeable. It is the objective of this article to review buccal drug delivery by discussing the structure and environment of the oral mucosa and the experimental methods used in assessing buccal drug permeation/absorption. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based deliv...

  2. Microemulsion Drug Delivery Systems for Radiopharmacy Studies

    Directory of Open Access Journals (Sweden)

    Emre Ozgenc

    2016-11-01

    Full Text Available Microemulsions have been used increasingly for last year’s because of ideal properties like favorable drug delivery, ease of preparation and physical stability. They have been improved the solubility and efficacy of the drug and reduce the side effects. Use of radiolabeled microemulsions plays an alternative role in drug delivery systems by investigating the formation, stability and application of microemulsions in radiopharmacy. Gama scintigraphic method is well recognized for developing and detecting the biodistribution of newly developed drugs or formulation. This review will focus on how radionuclides are able to play role with characterization studies of microemulsion drug delivery systems.

  3. Thiomers for oral delivery of hydrophilic macromolecular drugs.

    Science.gov (United States)

    Bernkop-Schnürch, Andreas; Hoffer, Martin H; Kafedjiiski, Krum

    2004-11-01

    In recent years thiolated polymers (thiomers) have appeared as a promising new tool in oral drug delivery. Thiomers are obtained by the immobilisation of thio-bearing ligands to mucoadhesive polymeric excipients. By the formation of disulfide bonds with mucus glycoproteins, the mucoadhesive properties of thiomers are up to 130-fold improved compared with the corresponding unmodified polymers. Owing to the formation of inter- and intramolecular disulfide bonds within the thiomer itself, matrix tablets and particulate delivery systems show strong cohesive properties, resulting in comparatively higher stability, prolonged disintegration times and a more controlled drug release. The permeation of hydrophilic macromolecular drugs through the gastrointestinal (GI) mucosa can be improved by the use of thiomers. Furthermore, some thiomers exhibit improved inhibitory properties towards GI peptidases. The efficacy of thiomers in oral drug delivery has been demonstrated by various in vivo studies. A pharmacological efficacy of 1%, for example, was achieved in rats by oral administration of calcitonin tablets comprising a thiomer. Furthermore, tablets comprising a thiomer and pegylated insulin resulted in a pharmacological efficacy of 7% after oral application to diabetic mice. Low-molecular-weight heparin embedded in thiolated polycarbophil led to an absolute bioavailability of > or = 20% after oral administration to rats. In these studies, formulations comprising the corresponding unmodified polymer had only a marginal or no effect. These results indicate drug carrier systems based on thiomers appear to be a promising tool for oral delivery of hydrophilic macromolecular drugs.

  4. 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.

  5. Permeation enhancer strategies in transdermal drug delivery.

    Science.gov (United States)

    Marwah, Harneet; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Today, ∼74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.

  6. Drug delivery glucantime in PVP/chitosan membranes

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Maria J.A.; Lugao, Ademar B.; Parra, Duclerc F., E-mail: mariajhho@yahoo.com.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Amato, Valdir S. [Universidade de Sao Paulo (DMIP/FM/USP), Sao Paulo, SP (Brazil). Faculdade de Medicina. Departamento de Molestias Infecciosas e Parasitarias

    2015-07-01

    The current study of polymer science considers the area of biomedical application very important to establish developments in new polymeric materials. Examples of that are hydrogels for controlled release of drugs. In this work, hydrogels of poly (N-2-vinil-pyrrolidone) (PVP) containing chitosan and clay nanoparticles were obtained and characterized to investigate chitosan influence on Glucantime drug delivery. The matrixes were crosslinked by gamma irradiation process with doses of 25 kGy. Hydrogels morphologies were observed by X Ray diffraction (DRX). Atomic Force Microscopy (AFM) and swelling kinetic at 22 °C to study the capacity of water retention and, finally, drug delivery tests were performed 'in vitro'. The system showed higher gel fraction for the matrix with 1.0% of clay and 0.5% of chitosan. In this case, besides the interactions of clay ions with PVP, there are interactions of chitosan amine group with PVP amide group. (author)

  7. Cell-penetrating peptides for drug delivery across membrane barriers

    DEFF Research Database (Denmark)

    Foged, Camilla; Nielsen, Hanne Moerck

    2008-01-01

    During the last decade, cell-penetrating peptides have been investigated for their ability to overcome the plasma membrane barrier of mammalian cells for the intracellular or transcellular delivery of cargoes as diverse as low molecular weight drugs, imaging agents, oligonucleotides, peptides......, proteins and colloidal carriers such as liposomes and polymeric nanoparticles. Their ability to cross biological membranes in a non-disruptive way without apparent toxicity is highly desired for increasing drug bioavailability. This review provides an overview of the application of cell......-penetrating peptides as transmembrane drug delivery agents, according to the recent literature, and discusses critical issues and future challenges in relation to fully understanding the fundamental principles of the cell-penetrating peptide-mediated membrane translocation of cargoes and the exploitation...

  8. Drug delivery glucantime in PVP/chitosan membranes

    International Nuclear Information System (INIS)

    Oliveira, Maria J.A.; Lugao, Ademar B.; Parra, Duclerc F.; Amato, Valdir S.

    2015-01-01

    The current study of polymer science considers the area of biomedical application very important to establish developments in new polymeric materials. Examples of that are hydrogels for controlled release of drugs. In this work, hydrogels of poly (N-2-vinil-pyrrolidone) (PVP) containing chitosan and clay nanoparticles were obtained and characterized to investigate chitosan influence on Glucantime drug delivery. The matrixes were crosslinked by gamma irradiation process with doses of 25 kGy. Hydrogels morphologies were observed by X Ray diffraction (DRX). Atomic Force Microscopy (AFM) and swelling kinetic at 22 °C to study the capacity of water retention and, finally, drug delivery tests were performed 'in vitro'. The system showed higher gel fraction for the matrix with 1.0% of clay and 0.5% of chitosan. In this case, besides the interactions of clay ions with PVP, there are interactions of chitosan amine group with PVP amide group. (author)

  9. 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.

  10. Thermoresponsive polymeric radionuclide delivery system - an injectable brachytherapy

    Czech Academy of Sciences Publication Activity Database

    Hrubý, Martin; Poučková, P.; Zadinová, M.; Kučka, Jan; Lebeda, Ondřej

    2011-01-01

    Roč. 42, č. 5 (2011), s. 484-488 ISSN 0928-0987 R&D Projects: GA ČR GPP207/10/P054; GA AV ČR IAAX00500803; GA MŠk 1M0505; GA MŠk 2B06165 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z10480505 Keywords : thermoresponsive polymer * brachytherapa * drug delivery Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.212, year: 2011

  11. Film forming systems for topical and transdermal drug delivery

    Directory of Open Access Journals (Sweden)

    Kashmira Kathe

    2017-11-01

    Full Text Available Skin is considered as an important route of administration of drugs for both local and systemic effects. The effectiveness of topical therapy depends on the physicochemical properties of the drug and adherence of the patient to the treatment regimen as well as the system's ability to adhere to skin during the therapy so as to promote drug penetration through the skin barrier. Conventional formulations for topical and dermatological administration of drugs have certain limitations like poor adherence to skin, poor permeability and compromised patient compliance. For the treatment of diseases of body tissues and wounds, the drug has to be maintained at the site of treatment for an effective period of time. Topical film forming systems are such developing drug delivery systems meant for topical application to the skin, which adhere to the body, forming a thin transparent film and provide delivery of the active ingredients to the body tissue. These are intended for skin application as emollient or protective and for local action or transdermal penetration of medicament for systemic action. The transparency is an appreciable feature of this polymeric system which greatly influences the patient acceptance. In the current discussion, the film forming systems are described as a promising choice for topical and transdermal drug delivery. Further the various types of film forming systems (sprays/solutions, gels and emulsions along with their evaluation parameters have also been reviewed.

  12. Protein-Based Drug-Delivery Materials

    OpenAIRE

    Jao, Dave; Xue, Ye; Medina, Jethro; Hu, Xiao

    2017-01-01

    There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based polymers are increasingly used for drug and vaccine delivery to cross these biological barriers and through blood circulation to their molecular site of action. Protein-based pol...

  13. Synthetic Lipoproteins as Carriers for Drug Delivery.

    Science.gov (United States)

    Huang, Gangliang; Liu, Yang; Huang, Hualiang

    2016-01-01

    Synthetic lipoprotein is an effective carrier of targeted delivery for drugs. It has the very small size, good biocompatibility, suitable half-life, and specific lipoprotein receptorbinding capacity. Compared with the traditional natural lipoprotein, synthetic lipoprotein not only retains the original biological characteristics and functions, but also exhibits the excellent characteristics in drug delivery. Herein, the advantages, development, applications, and prospect of synthetic lipoproteins as drug carriers were summarized.

  14. 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.

  15. Nanoscale drug delivery for targeted chemotherapy.

    Science.gov (United States)

    Xin, Yong; Huang, Qian; Tang, Jian-Qin; Hou, Xiao-Yang; Zhang, Pei; Zhang, Long Zhen; Jiang, Guan

    2016-08-28

    Despite significant improvements in diagnostic methods and innovations in therapies for specific cancers, effective treatments for neoplastic diseases still represent major challenges. Nanotechnology as an emerging technology has been widely used in many fields and also provides a new opportunity for the targeted delivery of cancer drugs. Nanoscale delivery of chemotherapy drugs to the tumor site is highly desirable. Recent studies have shown that nanoscale drug delivery systems not only have the ability to destroy cancer cells but may also be carriers for chemotherapy drugs. Some studies have demonstrated that delivery of chemotherapy via nanoscale carriers has greater therapeutic benefit than either treatment modality alone. In this review, novel approaches to nanoscale delivery of chemotherapy are described and recent progress in this field is discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Nanotechnology and Drug Delivery Part 2: Nanostructures for Drug ...

    African Journals Online (AJOL)

    Some challenges associated with the technology as it relates to drug effectiveness, toxicity, stability, pharmacokinetics and drug regulatory control are discussed in this review. Clearly, nanotechnology is a welcome development that is set to transform drug delivery and drug supply chain management, if optimally developed ...

  17. Self-assembled polymeric nanocarriers for the targeted delivery of retinoic acid to the hair follicle

    Science.gov (United States)

    Lapteva, Maria; Möller, Michael; Gurny, Robert; Kalia, Yogeshvar N.

    2015-11-01

    Acne vulgaris is a highly prevalent dermatological disease of the pilosebaceous unit (PSU). An inability to target drug delivery to the PSU results in poor treatment efficacy and the incidence of local side-effects. Cutaneous application of nanoparticulate systems is reported to induce preferential accumulation in appendageal structures. The aim of this work was to prepare stable polymeric micelles containing retinoic acid (RA) using a biodegradable and biocompatible diblock methoxy-poly(ethylene glycol)-poly(hexylsubstituted lactic acid) copolymer (MPEG-dihexPLA) and to evaluate their ability to deliver RA to skin. An innovative punch biopsy sample preparation method was developed to selectively quantify follicular delivery; the amounts of RA present were compared to those in bulk skin, (i.e. without PSU), which served as the control. RA was successfully incorporated into micelle nanocarriers and protected from photoisomerization by inclusion of Quinoline Yellow. Incorporation into the spherical, homogeneous and nanometer-scale micelles (dn 400-fold. Drug delivery experiments in vitro showed that micelles were able to deliver RA to porcine and human skins more efficiently than Retin-A® Micro (0.04%), a marketed gel containing RA loaded microspheres, (7.1 +/- 1.1% vs. 0.4 +/- 0.1% and 7.5 +/- 0.8% vs. 0.8 +/- 0.1% of the applied dose, respectively). In contrast to a non-colloidal RA solution, Effederm® (0.05%), both the RA loaded MPEG-dihexPLA polymeric micelles (0.005%) and Retin-A® Micro (0.04%) displayed selectivity for delivery to the PSU with 2-fold higher delivery to PSU containing samples than to control samples. Moreover, the micelle formulation outperformed Retin-A® Micro in terms of delivery efficiency to PSU presenting human skin (10.4 +/- 3.2% vs. 0.6 +/- 0.2%, respectively). The results indicate that the polymeric micelle formulation enabled an increased and targeted delivery of RA to the PSU, potentially translating to a safer and more efficient

  18. 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

  19. 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.

  20. Natural and synthetic biomaterials for controlled drug delivery.

    Science.gov (United States)

    Kim, Jang Kyoung; Kim, Hyung Jin; Chung, Jee-Young; Lee, Jong-Hwan; Young, Seok-Beom; Kim, Yong-Hee

    2014-01-01

    A wide variety of delivery systems have been developed and many products based on the drug delivery technology are commercially available. The development of controlled-release technologies accelerated new dosage form design by altering pharmacokinetic and pharmacodynamics profiles of given drugs, resulting in improved efficacy and safety. Various natural or synthetic polymers have been applied to make matrix, reservoir or implant forms due to the characteristics of polymers, especially ease of control for modifications of biocompatibility, biodegradation, porosity, charge, mechanical strength and hydrophobicity/hydrophilicity. Hydrogel is a hydrophilic, polymeric network capable of imbibing large amount of water and biological fluids. This review article introduces various applications of natural and synthetic polymer-based hydrogels from pharmaceutical, biomedical and bioengineering points of view.

  1. Current trends in the use of vitamin E-based micellar nanocarriers for anticancer drug delivery.

    Science.gov (United States)

    Muddineti, Omkara Swami; Ghosh, Balaram; Biswas, Swati

    2017-06-01

    Owing to the complexity of cancer pathogenesis, conventional chemotherapy can be an inadequate method of killing cancer cells effectively. Nanoparticle-based drug delivery systems have been widely exploited pre-clinically in recent years. Areas covered: Incorporation of vitamin-E in nanocarriers have the advantage of (1) improving the hydrophobicity of the drug delivery system, thereby improving the solubility of the loaded poorly soluble anticancer drugs, (2) enhancing the biocompatibility of the polymeric drug carriers, and (3) improving the anticancer potential of the chemotherapeutic agents by reversing the cellular drug resistance via simultaneous administration. In addition to being a powerful antioxidant, vitamin E demonstrated its anticancer potential by inducing apoptosis in various cancer cell lines. Various vitamin E analogs have proven their ability to cause marked inhibition of drug efflux transporters. Expert opinion: The review discusses the potential of incorporating vitamin E in the polymeric micelles which are designed to carry poorly water-soluble anticancer drugs. Current applications of various vitamin E-based polymeric micelles with emphasis on the use of α-tocopherol, D-α-tocopheryl succinate (α-TOS) and its conjugates such as D-α-tocopheryl polyethylene glycol-succinate (TPGS) in micellar system is delineated. Advantages of utilizing polymeric micelles for drug delivery and the challenges to treat cancer, including multiple drug resistance have been discussed.

  2. Smart Drug Delivery Systems in Cancer Therapy.

    Science.gov (United States)

    Unsoy, Gozde; Gunduz, Ufuk

    2018-02-08

    Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Protein-Based Drug-Delivery Materials

    Directory of Open Access Journals (Sweden)

    Dave Jao

    2017-05-01

    Full Text Available There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based polymers are increasingly used for drug and vaccine delivery to cross these biological barriers and through blood circulation to their molecular site of action. Protein-based polymers compared to synthetic polymers have the advantages of good biocompatibility, biodegradability, environmental sustainability, cost effectiveness and availability. This review addresses the sources of protein-based polymers, compares the similarity and differences, and highlights characteristic properties and functionality of these protein materials for sustained and controlled drug release. Targeted drug delivery using highly functional multicomponent protein composites to guide active drugs to the site of interest will also be discussed. A systematical elucidation of drug-delivery efficiency in the case of molecular weight, particle size, shape, morphology, and porosity of materials will then be demonstrated to achieve increased drug absorption. Finally, several important biomedical applications of protein-based materials with drug-delivery function—including bone healing, antibiotic release, wound healing, and corneal regeneration, as well as diabetes, neuroinflammation and cancer treatments—are summarized at the end of this review.

  4. Developing a Dissociative Nanocontainer for Peptide Drug Delivery

    Directory of Open Access Journals (Sweden)

    Patrick Kelly

    2015-10-01

    Full Text Available The potency, selectivity, and decreased side effects of bioactive peptides have propelled these agents to the forefront of pharmacological research. Peptides are especially promising for the treatment of neurological disorders and pain. However, delivery of peptide therapeutics often requires invasive techniques, which is a major obstacle to their widespread application. We have developed a tailored peptide drug delivery system in which the viral capsid of P22 bacteriophage is modified to serve as a tunable nanocontainer for the packaging and controlled release of bioactive peptides. Recent efforts have demonstrated that P22 nanocontainers can effectively encapsulate analgesic peptides and translocate them across blood-brain-barrier (BBB models. However, release of encapsulated peptides at their target site remains a challenge. Here a Ring Opening Metathesis Polymerization (ROMP reaction is applied to trigger P22 nanocontainer disassembly under physiological conditions. Specifically, the ROMP substrate norbornene (5-Norbornene-2-carboxylic acid is conjugated to the exterior of a loaded P22 nanocontainer and Grubbs II Catalyst is used to trigger the polymerization reaction leading to nanocontainer disassembly. Our results demonstrate initial attempts to characterize the ROMP-triggered release of cargo peptides from P22 nanocontainers. This work provides proof-of-concept for the construction of a triggerable peptide drug delivery system using viral nanocontainers.

  5. 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.

  6. Novel Polymeric Prodrugs of Valproic Acid as Anti- Epilepsy Drugs ...

    African Journals Online (AJOL)

    The release of VPA from polymeric prodrugs was studied using cellophane membrane dialysis bags containing aqueous buffer solutions (pH 1, 7 and 10) at 37 oC. The quantity of released drug was detected by ultraviolet (UV) spectroscopy. Results: 1H-NMR and elemental analyses data for calculating mole composition of ...

  7. 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.

  8. Chitosan microspheres in novel drug delivery systems.

    Science.gov (United States)

    Mitra, Analava; Dey, Baishakhi

    2011-07-01

    The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems.

  9. Drug delivery properties of macroporous polystyrene solid foams.

    Science.gov (United States)

    Canal, Cristina; Aparicio, Rosa Maria; Vilchez, Alejandro; Esquena, Jordi; García-Celma, Maria José

    2012-01-01

    Polymeric porous foams have been evaluated as possible new pharmaceutical dosage forms. These materials were obtained by polymerization in the continuous phase of highly concentrated emulsions prepared by the phase inversion temperature method. Their porosity, specific surface and surface topography were characterized, and the incorporation and release of active principles was studied using ketoprofen as model lipophilic molecule. Solid foams with very high pore volume, mainly inside macropores, were obtained by this method. The pore morphology of the materials was characterized, and very rough topography was observed, which contributed to their nearly superhydrophobic properties. These solid foams could be used as delivery systems for active principles with pharmaceutical interest, and in the present work ketoprofen was used as a model lipophilic molecule. Drug incorporation and release was studied from solid foam disks, using different concentrations of the loading solutions, achieving a delayed release with short lag-time.

  10. A cyclically actuated electrolytic drug delivery device

    KAUST Repository

    Yi, Ying; Buttner, Ulrich; Foulds, Ian G.

    2015-01-01

    This work, focusing on an implantable drug delivery system, presents the first prototype electrolytic pump that combines a catalytic reformer and a cyclically actuated mode. These features improve the release performance and extend the lifetime

  11. Brain tumor-targeted drug delivery strategies

    Directory of Open Access Journals (Sweden)

    Xiaoli Wei

    2014-06-01

    Full Text Available Despite the application of aggressive surgery, radiotherapy and chemotherapy in clinics, brain tumors are still a difficult health challenge due to their fast development and poor prognosis. Brain tumor-targeted drug delivery systems, which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue, are a promising new approach to brain tumor treatments. Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues, potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery. In this review, we briefly describe the physiological characteristics of brain tumors, including blood–brain/brain tumor barriers, the tumor microenvironment, and tumor stem cells. We also review targeted delivery strategies and introduce a systematic targeted drug delivery strategy to overcome the challenges.

  12. Patient's Guide to Aerosol Drug Delivery

    Science.gov (United States)

    ... these 3 different bad effects (or symptoms ) will bet- ter prepare you to understand the 5 categories ... in many ways that impact aerosol drug delivery. Thinking ability (under- standing how and when to use ...

  13. Polymeric anticancer drugs with pH-controlled activation

    Czech Academy of Sciences Publication Activity Database

    Ulbrich, Karel; Šubr, Vladimír

    2004-01-01

    Roč. 56, č. 7 (2004), s. 1023-1050 ISSN 0169-409X R&D Projects: GA ČR GA305/02/1425; GA AV ČR KSK4055109 Institutional research plan: CEZ:AV0Z4050913 Keywords : drug delivery * drug release * drug targeting Subject RIV: CC - Organic Chemistry Impact factor: 7.763, year: 2004

  14. Polymer based drug delivery systems for mycobacterial infections.

    Science.gov (United States)

    Pandey, Rajesh; Khuller, G K

    2004-07-01

    In the last decade, polymer based technologies have found wide biomedical applications. Polymers, whether synthetic (e.g. polylactide-co-glycolide or PLG) or natural (e.g. alginate, chitosan etc.), have the property of encapsulating a diverse range of molecules of biological interest and bear distinct therapeutic advantages such as controlled release of drugs, protection against the premature degradation of drugs and reduction in drug toxicity. These are important considerations in the long-duration treatment of chronic infectious diseases such as tuberculosis in which patient non-compliance is the major obstacle to successful chemotherapy. Antitubercular drugs, singly or in combination, have been encapsulated in polymers to provide controlled drug release and the system also offers the flexibility of selecting various routes of administration such as oral, subcutaneous and aerosol. The present review highlights the approaches towards the preparation of polymeric antitubercular drug delivery systems, emphasizing how the route of administration may influence drug bioavailability as well as the chemotherapeutic efficacy. In addition, the pros and cons of the various delivery systems are also discussed.

  15. Ion-Responsive Drug Delivery Systems.

    Science.gov (United States)

    Yoshida, Takayuki; Shakushiro, Kohsuke; Sako, Kazuhiro

    2018-02-08

    Some kinds of cations and anions are contained in body fluids such as blood, interstitial fluid, gastrointestinal juice, and tears at relatively high concentration. Ionresponsive drug delivery is available to design the unique dosage formulations which provide optimized drug therapy with effective, safe and convenient dosing of drugs. The objective of the present review was to collect, summarize, and categorize recent research findings on ion-responsive drug delivery systems. Ions in body fluid/formulations caused structural changes of polymers/molecules contained in the formulations, allow formulations exhibit functions. The polymers/molecules responding to ions were ion-exchange resins/fibers, anionic or cationic polymers, polymers exhibiting transition at lower critical solution temperature, self-assemble supramolecular systems, peptides, and metalorganic frameworks. The functions of ion-responsive drug delivery systems were categorized to controlled drug release, site-specific drug release, in situ gelation, prolonged retention at the target sites, and enhancement of drug permeation. Administration of the formulations via oral, ophthalmic, transdermal, and nasal routes has showed significant advantages in the recent literatures. Many kinds of drug delivery systems responding to ions have been reported recently for several administration routes. Improvement and advancement of these systems can maximize drugs potential and contribute to patients in the world. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Polymeric composite membranes for temperature and pH-responsive delivery of doxorubicin hydrochloride

    Directory of Open Access Journals (Sweden)

    Sahar Mohamaddoust Aliabadi

    2015-07-01

    Full Text Available Objective(s: Nowadays hydrogels are one of the upcoming classes of polymer-based controlled-release drug delivery systems. Temperature and pH-responsive delivery systems have drawn much attention because some diseases reveal themselves by a change in temperature and/or pH. The objective of this work is to prepare and characterize composite membrane using responsive nanoparticles into a polymer matrix. Materials and Methods: These nanoparticles were made of the copolymer poly (N-isopropylacrylamide-co-methaçrylic acid by an aqueous dispersion polymerization process and are responsible for dual sensitivity to temperature and pH. Morphology study with SEM, swelling behavior with Dynamic Light Scattering Technique, in vitro drug release behavior with side-by-side Diffusion Cells were also investigated in this paper. Doxorubicin hydrochloride was used as a model solute. Results:The study on the release of doxorubicin hydrochloride showed that the release rate was higher at pH 5 than pH 7.4, increased with the increase of temperature. Nevertheless, ionic strength only poses a minor direct effect at higher pH. Conclusion:Such system may be potentially used as a tumor-targeting doxorubicin hydrochloride delivery in the body.

  17. Nanomedicine Drug Delivery across Mucous Membranes

    Science.gov (United States)

    Lancina, Michael George, III

    Control over the distribution of therapeutic compounds is a complex and somewhat overlooked field of pharmaceutical research. When swallowing a pill or receiving an injection, it is commonly assumed that drug will spread throughout the body in a more or less uniform concentration and find its way to wherever it is needed. In truth, drug biodistribuition is highly non-uniform and dependent on a large number of factors. The development of advanced drug delivery systems to control biodistribution can produce significant advances in clinical treatments without the need to discover new therapeutic compounds. This work focuses on a number of nanostructured materials designed to improve drug delivery by direct and efficient transfer of drugs across one of the body's external mucous membranes. Chapter 1 outlines the central concept that unites these studies: nanomaterials and cationic particles can be used to delivery therapeutic compounds across mucous membranes. Special attention is given to dendritic nanoparticles. In chapter 2, uses for dendrimers in ocular drug delivery are presented. The studies are divided into two main groups: topical and injectable formulations. Chapter 3 does not involve dendrimers but instead another cationic particle used in transmembrane drug delivery, chitosan. Next, a dendrimer based nanofiber mat was used to deliver anti-glaucoma drugs in chapter 4. A three week in vivo efficacy trial showed dendrimer nanofiber mats outperformed traditional eye drops in terms of intra-ocular pressure decrease in a normotensive rat model. Finally, we have developed a new dendrimer based anti-glaucoma drug in chapter 5. Collectively, these studies demonstrate some of the potential applications for nanotechnology to improve transmembrane drug delivery. These particles and fibers are able to readily adhere and penetrate across epithelial cell lays. Utilizing these materials to improve drug absorption through these portals has the potential to improve the

  18. Microfluidic device for drug delivery

    Science.gov (United States)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2010-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  19. Mucus as a Barrier to Drug Delivery

    DEFF Research Database (Denmark)

    Bøgh, Marie; Nielsen, Hanne Mørck

    2015-01-01

    Viscoelastic mucus lines all mucosal surfaces of the body and forms a potential barrier to mucosal drug delivery. Mucus is mainly composed of water and mucins; high-molecular weight glycoproteins forming an entangled network. Consequently, mucus forms a steric barrier and due to its negative charge...... barrier to drug delivery. Current knowledge of mucus characteristics and barrier properties, as achieved by state-of-the-art methodologies, is the topic of this MiniReview emphasizing the gastrointestinal mucus and an overall focus on oral drug delivery. Cell culture-based in vitro models are well......, studies of peptide and protein drug diffusion in and through mucus and studies of mucus-penetrating nanoparticles are included to illustrate the mucus as a potentially important barrier to obtain sufficient bioavailability of orally administered drugs, and thus an important parameter to address...

  20. Microneedles for drug and vaccine delivery

    Science.gov (United States)

    Kim, Yeu-Chun; Park, Jung-Hwan; Prausnitz, Mark R.

    2012-01-01

    Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990’s when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications. PMID:22575858

  1. Chrono pharmacotherapy: A pulsatile Drug Delivery

    Directory of Open Access Journals (Sweden)

    Huma Hameed

    2015-01-01

    Full Text Available Chronopharmacotherapy refers to a treatment in which controlled drug delivery is achieved according to circadian rhythms of disease by enhancing therapeutic outcomes and minimizing side effects. Colon targeting has gained great importance not only for the treatment of local diseases such as Crohn’s disease, inflammatory bowel disease and ulcerative colitis but also very important in systemic delivery of proteins/peptides, antiasthmatic drugs, antidiabetic agents and antihypertensive drugs, which mostly show their efficacy based on circadian rhythms of the body.Colon drug delivery is one of the difficult approaches to achieve the targeted and desired outcomes through pulsatile drug delivery by avoiding dose dumping.The main reasonbehind the use of pulsatile delivery is provision ofconstant drug release where a zero-order release is notpreferred. Chronopharmacotherapy in colon targeting play its role bymany systems such ascapsular systems, pulsatile system and osmotic systems, which are based on use of rupturable membranes and biodegradable polymers.The objective of this review article is to provide latest knowledge about drugs with chrono-pharmacological behavior entails night time dosing specially to the colon.

  2. Calcium phosphate ceramics in drug delivery

    Science.gov (United States)

    Bose, Susmita; Tarafder, Solaiman; Edgington, Joe; Bandyopadhyay, Amit

    2011-04-01

    Calcium phosphate (CaP) particulates, cements and scaffolds have attracted significant interest as drug delivery vehicles. CaP systems, including both hydroxyapaptite and tricalcium phosphates, possess variable stoichiometry, functionality and dissolution properties which make them suitable for cellular delivery. Their chemical similarity to bone and thus biocompatibility, as well as variable surface charge density contribute to their controlled release properties. Among specific research areas, nanoparticle size, morphology, surface area due to porosity, and chemistry controlled release kinetics are the most active. This article discusses CaP systems in their particulate, cements, and scaffold forms for drug, protein, and growth factor delivery toward orthopedic and dental applications.

  3. Spray-on transdermal drug delivery systems.

    Science.gov (United States)

    Ibrahim, Sarah A

    2015-02-01

    Transdermal drug delivery possesses superior advantages over other routes of administration, particularly minimizing first-pass metabolism. Transdermal drug delivery is challenged by the barrier nature of skin. Numerous technologies have been developed to overcome the relatively low skin permeability, including spray-on transdermal systems. A transdermal spray-on system (TSS) usually consists of a solution containing the drug, a volatile solvent and in many cases a chemical penetration enhancer. TSS promotes drug delivery via the complex interplay between solvent evaporation and drug-solvent drag into skin. The volatile solvent carries the drug into the upper layers of the stratum corneum, and as the volatile solvent evaporates, an increase in the thermodynamic activity of the drug occurs resulting in an increased drug loading in skin. TSS is easily applied, delivering flexible drug dosage and associated with lower incidence of skin irritation. TSS provides a fast-drying product where the volatile solvent enables uniform drug distribution with minimal vehicle deposition on skin. TSS ensures precise dose administration that is aesthetically appealing and eliminates concerns of residual drug associated with transdermal patches. Furthermore, it provides a better alternative to traditional transdermal products due to ease of product development and manufacturing.

  4. Mucoadhesive Buccal Drug Delivery System

    OpenAIRE

    Pooja P.Thakkar; Meghana J.Chaudhari; Ami M.Soni; Dharti P.Pandya; Darshan A.Modi

    2012-01-01

    The buccal region of the oral cavity is an attractive target for administration of the drug of choice,particularly in overcoming deficiencies associated with the latter mode of administration. Problems suchas high first-pass metabolism and drug degradation in the gastrointestinal environment can becircumvented by administering the drug via the buccal route. Mucoadhesion can be defined as a state inwhich two components, of which one is of biological origin are held together for extended period...

  5. 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.

  6. Ocular Insert: Dosage Form for Sustain Opthalmic Drug Delivery

    Directory of Open Access Journals (Sweden)

    Sunil Kumar

    2012-06-01

    Full Text Available Except for skin, the eye is the most easily accessible site for topical administration of a medication. Traditional topical ophthalmic formulations (eye drops and ointments have poor bioavailability because of rapid pre-corneal elimination, conjunctival absorption, solution drainage by gravity, induced lacrimation and normal tear turnover. This leads to frequent installations of concentrated medication to achieve a therapeutic effect. The typical “pulse-entry” type drug release observed with ocular aqueous solutions (eye drops, suspensions and ointments can be replaced by more controlled, sustained, and continuous drug delivery, using a controlled-release ocular drug delivery system. Ocular inserts are solid or semisolid sterile preparations, of appropriate size and shape, designed to be inserted behind the eyelid or held on the eye and to deliver drugs for topical or systemic effect. These are polymeric systems into which the drug is incorporated as a solution or dispersion. They are better tolerated as to drainage and tear flow compared with other ophthalmic formulation and produce reliable drug release in the conjunctival cul-de-sac.

  7. Drug delivery's quest for polymers: Where are the frontiers?

    Science.gov (United States)

    Merkle, Hans P

    2015-11-01

    Since the legendary 1964 article of Folkman and Long entitled "The use of silicone rubber as a carrier for prolonged drug therapy" the role of polymers in controlled drug delivery has come a long way. Today it is evident that polymers play a crucial if not the prime role in this field. The latest boost owes to the interest in drug delivery for the purpose of tissue engineering in regenerative medicine. The focus of this commentary is on a selection of general and personal observations that are characteristic for the current state of polymer therapeutics and carriers. It briefly highlights selected examples for the long march of synthetic polymer-drug conjugates from bench to bedside, comments on the ambivalence of selected polymers as inert excipients versus biological response modifiers, and on the yet unsolved dilemma of cationic polymers for the delivery of nucleic acid therapeutics. Further subjects are the complex design of multifunctional polymeric carriers including recent concepts towards functional supramolecular polymers, as well as observations on stimuli-sensitive polymers and the currently ongoing trend towards natural and naturally-derived biopolymers. The final topic is the discovery and early development of a novel type of biodegradable polyesters for parenteral use. Altogether, it is not the basic and applied research in polymer therapeutics and carriers, but the translational process that is the key hurdle to proceed towards an authoritative approval of new polymer therapeutics and carriers. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Influence of microemulsions on cutaneous drug delivery

    DEFF Research Database (Denmark)

    Kreilgaard, Mads

    2002-01-01

    In attempt to increase cutaneous drug delivery, microemulsion vehicles have been more and more frequently employed over recent years. Microemulsion formulations have been shown to be superior for both transdermal and dermal delivery of particularly lipophilic compounds, but also hydrophilic...... compounds appear to benefit from application in microemulsions compared to conventional vehicles, like hydrogels, emulsions and liposomes. The favourable drug delivery properties of microemulsions appear to mainly be attributed to the excellent solubility properties. However, the vehicles may also act...... as penetration enhancers depending on the oil/surfactant constituents, which involves a risk of inducing local irritancy. The correlation between microemulsion structure/composition and drug delivery potential is not yet fully elucidated. However, a few studies have indicated that the internal structure...

  9. A pulsed mode electrolytic drug delivery device

    KAUST Repository

    Yi, Ying; Buttner, Ulrich; Carreno, Armando Arpys Arevalo; Conchouso Gonzalez, David; Foulds, Ian G.

    2015-01-01

    This paper reports the design of a proof-of-concept drug delivery device that is actuated using the bubbles formed during electrolysis. The device uses a platinum (Pt) coated nickel (Ni) metal foam and a solid drug in reservoir (SDR) approach

  10. A wireless actuating drug delivery system

    International Nuclear Information System (INIS)

    Jo, Won-Jun; Baek, Seung-Ki; Park, Jung-Hwan

    2015-01-01

    A wireless actuating drug delivery system was devised. The system is based on induction heating for drug delivery. In this study, thermally generated nitrogen gas produced by induction heating of azobisisobutyronitrile (AIBN) was utilized for pressure-driven release of the drug. The delivery device consists of an actuator chamber, a drug reservoir, and a microchannel. A semicircular copper disc (5 and 6 mm in diameter and 100 µm thick), and thermal conductive tape were integrated as the heating element in the actuator chamber. The final device was 2.7 mm thick. 28 µl of drug solution were placed in the reservoir and the device released the drug quickly at the rate of 6 µl s −1 by induction heating at 160 µT of magnetic intensity. The entire drug solution was released and dispersed after subcutaneous implantation under identical experimental condition. This study demonstrates that the device was simply prepared and drug delivery could be achieved by wireless actuation of a thin, pressure-driven actuator. (paper)

  11. A cyclically actuated electrolytic drug delivery device

    KAUST Repository

    Yi, Ying

    2015-01-01

    This work, focusing on an implantable drug delivery system, presents the first prototype electrolytic pump that combines a catalytic reformer and a cyclically actuated mode. These features improve the release performance and extend the lifetime of the device. Using our platinum (Pt)-coated carbon fiber mesh that acts as a catalytic reforming element, the cyclical mode is improved because the faster recombination rate allows for a shorter cycling time for drug delivery. Another feature of our device is that it uses a solid-drug-in-reservoir (SDR) approach, which allows small amounts of a solid drug to be dissolved in human fluid, forming a reproducible drug solution for long-term therapies. We have conducted proof-of-principle drug delivery studies using such an electrolytic pump and solvent blue 38 as the drug substitute. These tests demonstrate power-controlled and pulsatile release profiles of the chemical substance, as well as the feasibility of this device. A drug delivery rate of 11.44 ± 0.56 μg min-1 was achieved by using an input power of 4 mW for multiple pulses, which indicates the stability of our system. © The Royal Society of Chemistry 2015.

  12. Chemical Penetration Enhancers for Transdermal Drug Delivery ...

    African Journals Online (AJOL)

    for transdermal administration. The permeation of drug through skin can be enhanced by both chemical penetration enhancement and physical methods. In this review, we have discussed the chemical penetration enhancement technology for transdermal drug delivery as well as the probable mechanisms of action.

  13. A pulsed mode electrolytic drug delivery device

    International Nuclear Information System (INIS)

    Yi, Ying; Foulds, Ian G; Buttner, Ulrich; Carreno, Armando A A; Conchouso, David

    2015-01-01

    This paper reports the design of a proof-of-concept drug delivery device that is actuated using the bubbles formed during electrolysis. The device uses a platinum (Pt) coated nickel (Ni) metal foam and a solid drug in reservoir (SDR) approach to improve the device’s performance. This electrochemically-driven pump has many features that are unlike conventional drug delivery devices: it is capable of pumping periodically and being refilled automatically; it features drug release control; and it enables targeted delivery. Pt-coated metal foam is used as a catalytic reforming element, which reduces the period of each delivery cycle. Two methods were used for fabricating the Pt-coated metal: sputtering and electroplating. Of these two methods, the sputtered Pt-coated metal foam has a higher pumping rate; it also has a comparable recombination rate when compared to the electroplated Pt-coated metal foam. The only drawback of this catalytic reformer is that it consumes nickel scaffold. Considering long-term applications, the electroplated Pt metal foam was selected for drug delivery, where a controlled drug release rate of 2.2 μg  ±  0.3 μg per actuation pulse was achieved using 4 mW of power. (paper)

  14. A pulsed mode electrolytic drug delivery device

    KAUST Repository

    Yi, Ying

    2015-09-14

    This paper reports the design of a proof-of-concept drug delivery device that is actuated using the bubbles formed during electrolysis. The device uses a platinum (Pt) coated nickel (Ni) metal foam and a solid drug in reservoir (SDR) approach to improve the device\\'s performance. This electrochemically-driven pump has many features that are unlike conventional drug delivery devices: it is capable of pumping periodically and being refilled automatically; it features drug release control; and it enables targeted delivery. Pt-coated metal foam is used as a catalytic reforming element, which reduces the period of each delivery cycle. Two methods were used for fabricating the Pt-coated metal: sputtering and electroplating. Of these two methods, the sputtered Pt-coated metal foam has a higher pumping rate; it also has a comparable recombination rate when compared to the electroplated Pt-coated metal foam. The only drawback of this catalytic reformer is that it consumes nickel scaffold. Considering long-term applications, the electroplated Pt metal foam was selected for drug delivery, where a controlled drug release rate of 2.2 μg ± 0.3 μg per actuation pulse was achieved using 4 mW of power.

  15. Sustained Release Drug Delivery Applications of Polyurethanes

    Directory of Open Access Journals (Sweden)

    Michael B. Lowinger

    2018-05-01

    Full Text Available Since their introduction over 50 years ago, polyurethanes have been applied to nearly every industry. This review describes applications of polyurethanes to the development of modified release drug delivery. Although drug delivery research leveraging polyurethanes has been ongoing for decades, there has been renewed and substantial interest in the field in recent years. The chemistry of polyurethanes and the mechanisms of drug release from sustained release dosage forms are briefly reviewed. Studies to assess the impact of intrinsic drug properties on release from polyurethane-based formulations are considered. The impact of hydrophilic water swelling polyurethanes on drug diffusivity and release rate is discussed. The role of pore formers in modulating drug release rate is examined. Finally, the value of assessing mechanical properties of the dosage form and approaches taken in the literature are described.

  16. Computational Amphiphilic Materials for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Naresh eThota

    2015-10-01

    Full Text Available Amphiphilic materials can assemble into a wide variety of morphologies and have emerged as a novel class of candidates for drug delivery. Along with a large number of experiments reported, computational studies have been also conducted in this field. At an atomistic/molecular level, computations can facilitate quantitative understanding of experimental observations and secure fundamental interpretation of underlying phenomena. This review summarizes the recent computational efforts on amphiphilic copolymers and peptides for drug delivery. Atom-resolution and time-resolved insights are provided from bottom-up to microscopically elucidate the mechanisms of drug loading/release, which are indispensable in the rational screening and design of new amphiphiles for high-efficacy drug delivery.

  17. Recombinant Amphiphilic Protein Micelles for Drug Delivery

    OpenAIRE

    Kim, Wookhyun; Xiao, Jiantao; Chaikof, Elliot L.

    2011-01-01

    Amphiphilic block polypeptides can self-assemble into a range of nanostructures in solution, including micelles and vesicles. Our group has recently described the capacity of recombinant amphiphilic diblock copolypeptides to form highly stable micelles. In this report, we demonstrate the utility of protein nanoparticles to serve as a vehicle for controlled drug delivery. Drug-loaded micelles were produced by encapsulating dipyridamole as a model hydrophobic drug with anti-inflammatory activit...

  18. 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.

  19. Trojan Microparticles for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Thierry F. Vandamme

    2012-01-01

    Full Text Available During the last decade, the US Food and Drug Administration (FDA have regulated a wide range of products, (foods, cosmetics, drugs, devices, veterinary, and tobacco which may utilize micro and nanotechnology or contain nanomaterials. Nanotechnology allows scientists to create, explore, and manipulate materials in nano-regime. Such materials have chemical, physical, and biological properties that are quite different from their bulk counterparts. For pharmaceutical applications and in order to improve their administration (oral, pulmonary and dermal, the nanocarriers can be spread into microparticles. These supramolecular associations can also modulate the kinetic releases of drugs entrapped in the nanoparticles. Different strategies to produce these hybrid particles and to optimize the release kinetics of encapsulated drugs are discussed in this review.

  20. Drug Delivery Research: The Invention Cycle.

    Science.gov (United States)

    Park, Kinam

    2016-07-05

    Controlled drug delivery systems have been successful in introducing improved formulations for better use of existing drugs and novel delivery of biologicals. The initial success of producing many oral products and some injectable depot formulations, however, reached a plateau, and the progress over the past three decades has been slow. This is likely due to the difficulties of formulating hydrophilic, high molecular weight drugs, such as proteins and nucleic acids, for targeting specific cells, month-long sustained delivery, and pulsatile release. Since the approaches that have served well for delivery of small molecules are not applicable to large molecules, it is time to develop new methods for biologicals. The process of developing future drug delivery systems, termed as the invention cycle, is proposed, and it starts with clearly defining the problems for developing certain formulations. Once the problems are well-defined, creative imagination examines all potential options and selects the best answer and alternatives. Then, innovation takes over to generate unique solutions for developing new formulations that resolve the previously identified problems. Ultimately, the new delivery systems will have to go through a translational process to produce the final formulations for clinical use. The invention cycle also emphasizes examining the reasons for success of certain formulations, not just the reasons for failure of many systems. Implementation of the new invention cycle requires new mechanisms of funding the younger generation of scientists and a new way of identifying their achievements, thereby releasing them from the burden of short-termism.

  1. Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs.

    Science.gov (United States)

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse; Yang, Mingshi; Nielsen, Hanne Mørck; Mu, Huiling

    2015-01-01

    Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract are summarized. Additionally, the paper provides an overview of recent studies on characterization of solid drug carriers for peptide/protein drugs, drug distribution in particles, drug release and stability in simulated GI fluids, as well as the absorption of peptide/protein drugs in cell-based models. The use of biorelevant media when applicable can increase the knowledge about the quality of DDS for oral protein delivery. Hopefully, the knowledge provided in this review will aid the establishment of improved biorelevant models capable of forecasting the performance of particulate DDS for oral peptide/protein delivery.

  2. Premature drug release of polymeric micelles and its effects on tumor targeting.

    Science.gov (United States)

    Miller, Tobias; Breyer, Sandra; van Colen, Gwenaelle; Mier, Walter; Haberkorn, Uwe; Geissler, Simon; Voss, Senta; Weigandt, Markus; Goepferich, Achim

    2013-03-10

    Based on the enhanced permeability and retention (EPR) effect, nanoparticles are believed to accumulate in tumors. In this conjunction, the stability of drug encapsulation is assumed to be sufficient. For clarification purposes, PEGylated poly-(D,L-lactic acid) (PEG-PDLLA) micelles which incorporated the hydrophobic model drug dechloro-4-iodo-fenofibrate (IFF) were investigated. H2N-PEG-PDLLA was synthesized, coupled to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and labeled with 111-indium. From this polymeric species, mixed micelles with H3CO-PEG-PDLLA were prepared which encapsulated the 125-iodine or 131-iodine labeled drug IFF. Bioimaging and biodistribution experiments in healthy and AR42J-tumor bearing mice were carried out to quantify the uptake of the drug and its carrier in single organs. As a result, upon injection of this system, a rapid dissociation of the polymeric carrier and the incorporated drug (system allowed for successful solubilization of the hydrophobic drug by physical incorporation into micelles whereas the tumor targeting properties of the drug delivery system could not be sufficiently shown. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Controlling fungal biofilms with functional drug delivery denture biomaterials.

    Science.gov (United States)

    Wen, Jianchuan; Jiang, Fuguang; Yeh, Chih-Ko; Sun, Yuyu

    2016-04-01

    Candida-associated denture stomatitis (CADS), caused by colonization and biofilm-formation of Candida species on denture surfaces, is a significant clinical concern. We show here that modification of conventional denture materials with functional groups can significantly increase drug binding capacity and control drug release rate of the resulting denture materials for potentially managing CADS. In our approach, poly(methyl methacrylate) (PMMA)-based denture resins were surface grafted with three kinds of polymers, poly(1-vinyl-2-pyrrolidinone) (PNVP), poly(methacrylic acid) (PMAA), and poly(2-hydroxyethyl methacrylate) (PHEMA), through plasma-initiated grafting polymerization. With a grafting yield as low as 2 wt%, the three classes of new functionalized denture materials showed significantly higher drug binding capacities toward miconazole, a widely used antifungal drug, than the original PMMA denture resin control, leading to sustained drug release and potent biofilm-controlling effects against Candida. Among the three classes of functionalized denture materials, PNVP-grafted resin provided the highest miconazole binding capability and the most powerful antifungal and biofilm-controlling activities. Drug binding mechanisms were studied. These results demonstrated the importance of specific interactions between drug molecules and functional groups on biomaterials, shedding lights on future design of CADS-managing denture materials and other related devices for controlled drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs.

    Science.gov (United States)

    Wang, Xue-Qing; Zhang, Qiang

    2012-10-01

    pH-sensitive polymeric nanoparticles are promising for oral drug delivery, especially for peptide/protein drugs and poorly water-soluble medicines. This review describes current status of pH-sensitive polymeric nanoparticles for oral drug delivery and introduces the mechanisms of drug release from them as well as possible reasons for absorption improvement, with emphasis on our contribution to this field. pH-sensitive polymeric nanoparticles are prepared mainly with polyanions, polycations, their mixtures or cross-linked polymers. The mechanisms of drug release are the result of carriers' dissolution, swelling or both of them at specific pH. The possible reasons for improvement of oral bioavailability include the following: improve drug stability, enhance mucoadhesion, prolong resident time in GI tract, ameliorate intestinal permeability and increase saturation solubility and dissolution rate for poorly water-soluble drugs. As for the advantages of pH-sensitive nanoparticles over conventional nanoparticles, we conclude that (1) most carriers used are enteric-coating materials and their safety has been approved. (2) The rapid dissolution or swelling of carriers at specific pH results in quick drug release and high drug concentration gradient, which is helpful for absorption. (3) At the specific pH carriers dissolve or swell, and the bioadhesion of carriers to mucosa becomes high because nanoparticles turn from solid to gel, which can facilitate drug absorption. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. 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

  6. Loading of microcontainers for oral drug delivery

    DEFF Research Database (Denmark)

    Marizza, Paolo

    The pharmaceutical research is facing several obstacles in the development of drug products for the oral delivery. The main problem deals with the intrinsic chemical nature of the new drug candidates, which are often poorly soluble and barely absorbed in the gastro-intestinal tract. Furthermore......, they are usually degraded before they are absorbed. These combined factors considerably reduce the bioavailability of many active ingredients. Several strategies have been developed to overcome these challenges. One of them are microfabricated drug delivery devices. Microreservoir based-systems are characterized...... of UV photolithography was developed. The fabrication of polymer patterns was optimized and loading with both small hydrophobic drugs and proteins was demonstrated. Finally, structural properties of hydrogels were elucidated by rheology and NMR with the perspective of controlling the drug release...

  7. Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs

    DEFF Research Database (Denmark)

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse

    2015-01-01

    Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe...... delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract...... biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral...

  8. Stimuli-Responsive Liposomes for Controlled Drug Delivery

    KAUST Repository

    Li, Wengang

    2014-09-01

    Liposomes are promising drug delivery vesicles due to their biodegradibility, large volume and biocompatibility towards both hydrophilic and hydrophobic drugs. They suffer, however, from poor stability which limits their use in controlled delivery applications. Herein, a novel method was devised for modification of liposomes with small molecules, polymers or nanoparticles to afford stimuli responsive systems that release on demand and stay relatively stable in the absence of the trigger.. This dissertation discusses thermosensitive, pH sensitive, light sensitive and magnetically triggered liposomes that have been prepared for controlled drug delivery application. RAFT polymerization was utilized for the preparation of thermosensitive liposomes (Cholesterol-PNIPAm) and acid-labile liposomes (DOPE-PAA). With low Mw Cholesterol-PNIPAm, the thermosensitive liposomes proved to be effective for controlled release and decreased the cytotoxicity of PNIPAm by eliciting the polymer doses. By crosslinking the DOPE-PAA on liposome surface with acid-labile diamine linkers, DOPE-PAA liposomes were verified to be sensitive at low pH. The effects of polymer structures (linear or hyperbranched) have also been studied for the stability and release properties of liposomes. Finally, a dual-responsive Au@SPIO embedded liposome hybrid (ALHs) was prepared with light-induced “on-and-off” function by photo-thermal process (visible light) and instant release properties triggered by alternating magnetic field, respectively. The ALH system would be further applied into the cellular imaging field as MRI contrast agent.

  9. Albumin and its application in drug delivery.

    Science.gov (United States)

    Sleep, Darrell

    2015-05-01

    Rapid clearance of drugs from the body results in short therapeutic half-life and is an integral property of many protein and peptide-based drugs. To maintain the desired therapeutic effect patients are required to administer higher doses more frequently, which is inconvenient and risks undesirable side effects. Drug delivery technologies aim to minimise the number of administrations and dose-related toxicity while maximising therapeutic efficacy. This review describes albumin's inherent biochemical and biophysical properties, which make it an attractive drug delivery platform and the developmental status of drugs that are associated, conjugated or genetically fused with albumin. Albumin interacts with a number of cell surface receptors including gp18, gp30, gp60, FcRn, cubilin and megalin. The importance of albumin's interaction with the FcRn receptor, the basis for albumin's long circulatory half-life, is described, as are engineered albumins with improved pharmacokinetics. Albumin naturally accumulates at tumours and sites of inflammation, a characteristic which can be augmented by the addition of targeting ligands. The development of albumin drug conjugates which reply upon this property is described. Albumin's inherent biochemical and biophysical properties make it an ideal drug delivery platform. Recent advances in our understanding of albumin physiology and the improvement in albumin-based therapies strongly suggest that albumin-based therapies have a significant advantage over alternative technologies in terms of half-life, stability, versatility, safety and ease of manufacture. Given the importance of the albumin:FcRn interaction, the interpretation of the pharmacokinetic and pharmacodynamic profiles of albumin-based therapeutics with disturbed albumin:FcRn interaction may have to be reassessed. The FcRn receptor has additional functionality, especially in relation to immunology, antigen presentation and delivery of proteins across mucosal membranes

  10. Aptamers for Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Partha Ray

    2010-05-01

    Full Text Available Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX. SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery.

  11. Preparation of grafted microspheres CPVA-g-PSSS and studies on their drug-carrying and colon-specific drug delivery properties

    International Nuclear Information System (INIS)

    Gao, Baojiao; Fang, Li; Men, Jiying; Zhang, Yanyan

    2013-01-01

    Sodium 4-styrene sulfonate (SSS) was graft-polymerized on the surfaces of crosslinked polyvinyl alcohol (CPVA) microspheres in a manner of surface-initiated graft-polymerization by using cerium salt-hydroxyl group redox initiation system, obtaining the grafted microspheres CPVA-g-PSSS. The chemical structure and physicochemical characters of CPVA-g-PSSS microspheres were fully characterized with infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and zeta potential determination. The aim of this work is to constitute a novel colon-specific drug delivery system via molecular design by using CPVA-g-PSSS microspheres as the drug-carrying material and by taking metronidazole (MTZ) as the model drug. The drug-carrying ability and mechanism of the grafted microspheres CPVA-g-PSSS for MTZ were investigated. Finally, in-vitro release tests for the drug-carrying microspheres were conducted. The experimental results show that in an acidic medium, the grafted microspheres CPVA-g-PSSS exhibit strong adsorption ability for MTZ by driving of electrostatic interaction, and have an adsorption capacity of 112 mg/g, displaying the high efficiency of drug-carrying. The in-vitro release behavior of the drug-carried microspheres is highly pH-sensitive. In the medium of pH = 1, the drug-carrying microspheres do not release the drug, whereas in the medium of pH = 7.4, a sudden delivery phenomenon of the drug will occur, displaying an excellent colon-specific drug delivery behavior. Highlights: ► A metronidazole colon-specific drug delivery was constituted using grafted polymeric microspheres. ► Grafted polymeric microspheres CPVA-g-PSSS were prepared via surface-initiated graft-polymerization. ► The release of the drug-carrying microspheres is highly pH-sensitive. ► The drug-carrying microspheres display an excellent colon-specific drug delivery behavior

  12. Preparation of grafted microspheres CPVA-g-PSSS and studies on their drug-carrying and colon-specific drug delivery properties

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Baojiao, E-mail: gaobaojiao@126.com [Department of Chemical Engineering, North University of China, Taiyuan 030051, People' s Republic of China (China); Fang, Li [School of Chemistry and Chemical engineering, Shanxi University, Taiyuan 030006 (China); Men, Jiying; Zhang, Yanyan [Department of Chemical Engineering, North University of China, Taiyuan 030051, People' s Republic of China (China)

    2013-04-01

    Sodium 4-styrene sulfonate (SSS) was graft-polymerized on the surfaces of crosslinked polyvinyl alcohol (CPVA) microspheres in a manner of surface-initiated graft-polymerization by using cerium salt-hydroxyl group redox initiation system, obtaining the grafted microspheres CPVA-g-PSSS. The chemical structure and physicochemical characters of CPVA-g-PSSS microspheres were fully characterized with infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and zeta potential determination. The aim of this work is to constitute a novel colon-specific drug delivery system via molecular design by using CPVA-g-PSSS microspheres as the drug-carrying material and by taking metronidazole (MTZ) as the model drug. The drug-carrying ability and mechanism of the grafted microspheres CPVA-g-PSSS for MTZ were investigated. Finally, in-vitro release tests for the drug-carrying microspheres were conducted. The experimental results show that in an acidic medium, the grafted microspheres CPVA-g-PSSS exhibit strong adsorption ability for MTZ by driving of electrostatic interaction, and have an adsorption capacity of 112 mg/g, displaying the high efficiency of drug-carrying. The in-vitro release behavior of the drug-carried microspheres is highly pH-sensitive. In the medium of pH = 1, the drug-carrying microspheres do not release the drug, whereas in the medium of pH = 7.4, a sudden delivery phenomenon of the drug will occur, displaying an excellent colon-specific drug delivery behavior. Highlights: ► A metronidazole colon-specific drug delivery was constituted using grafted polymeric microspheres. ► Grafted polymeric microspheres CPVA-g-PSSS were prepared via surface-initiated graft-polymerization. ► The release of the drug-carrying microspheres is highly pH-sensitive. ► The drug-carrying microspheres display an excellent colon-specific drug delivery behavior.

  13. Clinical developments of chemotherapeutic nanomedicines: Polymers and liposomes for delivery of camptothecins and platinum (II) drugs

    KAUST Repository

    Kieler-Ferguson, Heidi M.

    2013-01-17

    For the past 40 years, liposomal and polymeric delivery vehicles have been studied as systems capable of modulating the cytotoxicity of small molecule chemotherapeutics, increasing tumor bearing animal survival times, and improving drug targeting. Although a number of macromolecular-drug conjugates have progressed to clinical trials, tuning drug release to maintain efficacy in conjunction with controlling drug toxicity has prevented the clinical adoption of many vehicles. In this article, we review the motivations for and approaches to polymer and liposomal delivery with regard to camptothecin and cisplatin delivery. WIREs Nanomed Nanobiotechnol 2013, 5:130-138. doi: 10.1002/wnan.1209 For further resources related to this article, please visit the WIREs website. Conflict of interest: Drs Kieler-Ferguson and Fréchet declare no conflicts of interest. Dr Szoka is the founder of a liposome drug delivery company that is not working on any of the compounds mentioned in this article. © 2013 Wiley Periodicals, Inc.

  14. Plasmon resonant liposomes for controlled drug delivery

    Science.gov (United States)

    Knights-Mitchell, Shellie S.; Romanowski, Marek

    2015-03-01

    Nanotechnology use in drug delivery promotes a reduction in systemic toxicity, improved pharmacokinetics, and better drug bioavailability. Liposomes continue to be extensively researched as drug delivery systems (DDS) with formulations such as Doxil® and Ambisome® approved by FDA and successfully marketed in the United States. However, the limited ability to precisely control release of active ingredients from these vesicles continues to challenge the broad implementation of this technology. Moreover, the full potential of the carrier to sequester drugs until it can reach its intended target has yet to be realized. Here, we describe a liposomal DDS that releases therapeutic doses of an anticancer drug in response to external stimulus. Earlier, we introduced degradable plasmon resonant liposomes. These constructs, obtained by reducing gold on the liposome surface, facilitate spatial and temporal release of drugs upon laser light illumination that ultimately induces an increase in temperature. In this work, plasmon resonant liposomes have been developed to stably encapsulate and retain doxorubicin at physiological conditions represented by isotonic saline at 37o C and pH 7.4. Subsequently, they are stimulated to release contents either by a 5o C increase in temperature or by laser illumination (760 nm and 88 mW/cm2 power density). Successful development of degradable plasmon resonant liposomes responsive to near-infrared light or moderate hyperthermia can provide a new delivery method for multiple lipophilic and hydrophilic drugs with pharmacokinetic profiles that limit clinical utility.

  15. 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.

  16. Drug delivery approaches for breast cancer

    Directory of Open Access Journals (Sweden)

    Singh SK

    2017-08-01

    Full Text Available Santosh Kumar Singh,1 Shriti Singh,2 James W Lillard Jr,1 Rajesh Singh1 1Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA; 2Department of Kriya Sharir, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India Abstract: Breast cancer is one of the most common cancers affecting women worldwide. The controlled release of drugs to the precise site of the disease using a nanocarrier vehicle increases the therapeutic efficiency of the drugs. Nanotechnology-based approaches used to endorse clinical improvement from a disease also help to understand the interaction of malignant cells with their microenvironment. Receptor-based targeting is another approach for drug delivery which is undergoing clinical trials. Nanoparticles (NPs delivery has been proven to promise high loading capacity, less toxicity, and stability of the drugs or biomolecules compared to traditional chemotherapeutic drugs. The goal of this review is to present the current problems of breast cancer therapy and discuss the NP-based targeting to overcome the hurdles of conventional drug therapy approach. Keywords: breast cancer, nanoparticles, drug delivery systems

  17. Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues

    Directory of Open Access Journals (Sweden)

    Kanika Madaan

    2014-01-01

    Full Text Available Dendrimers are the emerging polymeric architectures that are known for their defined structures, versatility in drug delivery and high functionality whose properties resemble with biomolecules. These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach respectively. Moreover, high ratio of surface groups to molecular volume has made them a promising synthetic vector for gene delivery. Owing to these properties dendrimers have fascinated the researchers in the development of new drug carriers and they have been implicated in many therapeutic and biomedical applications. Despite of their extensive applications, their use in biological systems is limited due to toxicity issues associated with them. Considering this, the present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity.

  18. Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues

    Science.gov (United States)

    Madaan, Kanika; Kumar, Sandeep; Poonia, Neelam; Lather, Viney; Pandita, Deepti

    2014-01-01

    Dendrimers are the emerging polymeric architectures that are known for their defined structures, versatility in drug delivery and high functionality whose properties resemble with biomolecules. These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach) respectively. Moreover, high ratio of surface groups to molecular volume has made them a promising synthetic vector for gene delivery. Owing to these properties dendrimers have fascinated the researchers in the development of new drug carriers and they have been implicated in many therapeutic and biomedical applications. Despite of their extensive applications, their use in biological systems is limited due to toxicity issues associated with them. Considering this, the present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity. PMID:25035633

  19. Intracranial drug delivery for subarachnoid hemorrhage.

    Science.gov (United States)

    Macdonald, Robert Loch; Leung, Ming; Tice, Tom

    2012-01-01

    Tice and colleagues pioneered site-specific, sustained-release drug delivery to the brain almost 30 years ago. Currently there is one drug approved for use in this manner. Clinical trials in subarachnoid hemorrhage have led to approval of nimodipine for oral and intravenous use, but other drugs, such as clazosentan, hydroxymethylglutaryl CoA reductase inhibitors (statins) and magnesium, have not shown consistent clinical efficacy. We propose that intracranial delivery of drugs such as nimodipine, formulated in sustained-release preparations, are good candidates for improving outcome after subarachnoid hemorrhage because they can be administered to patients that are already undergoing surgery and who have a self-limited condition from which full recovery is possible.

  20. Nanoparticulate delivery systems for antiviral drugs.

    Science.gov (United States)

    Lembo, David; Cavalli, Roberta

    2010-01-01

    Nanomedicine opens new therapeutic avenues for attacking viral diseases and for improving treatment success rates. Nanoparticulate-based systems might change the release kinetics of antivirals, increase their bioavailability, improve their efficacy, restrict adverse drug side effects and reduce treatment costs. Moreover, they could permit the delivery of antiviral drugs to specific target sites and viral reservoirs in the body. These features are particularly relevant in viral diseases where high drug doses are needed, drugs are expensive and the success of a therapy is associated with a patient's adherence to the administration protocol. This review presents the current status in the emerging area of nanoparticulate delivery systems in antiviral therapy, providing their definition and description, and highlighting some peculiar features. The paper closes with a discussion on the future challenges that must be addressed before the potential of nanotechnology can be translated into safe and effective antiviral formulations for clinical use.

  1. Drug delivery system and radiation therapy

    International Nuclear Information System (INIS)

    Shibata, Tokushi

    2005-01-01

    This paper describes the review of radiation therapy, neutron capture therapy (NCT) and drug delivery system for the latter. In cancer radiation therapy, there are problems of body movement like breathing, needless irradiation of normal tissues, difficulty to decide the correct irradiation position and tumor morphology. NCT has advantages to overcome these, and since boron has a big cross section for thermal neutron, NPT uses the reaction 10 B(n, α) 7 Li in the target cancer which previously incorporated the boron-containing drug. During the period 1966-1996, 246 patients were treated with this in Japan and the treatment has been continued thereafter. The tasks for NCT are developments of drug delivery system efficient to deliver the drug into the tumor and of convenient neutron source like the accelerator. (S.I.)

  2. Recent Advances in Ocular Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Shinobu Fujii

    2011-01-01

    Full Text Available Transport of drugs applied by traditional dosage forms is restricted to the eye, and therapeutic drug concentrations in the target tissues are not maintained for a long duration since the eyes are protected by a unique anatomy and physiology. For the treatment of the anterior segment of the eye, various droppable products to prolong the retention time on the ocular surface have been introduced in the market. On the other hand, direct intravitreal implants, using biodegradable or non-biodegradable polymer technology, have been widely investigated for the treatment of chronic vitreoretinal diseases. There is urgent need to develop ocular drug delivery systems which provide controlled release for the treatment of chronic diseases, and increase patient’s and doctor’s convenience to reduce the dosing frequency and invasive treatment. In this article, progress of ocular drug delivery systems under clinical trials and in late experimental stage is reviewed.

  3. Thiolated Chitosan Masked Polymeric Microspheres with Incorporated Mesocellular Silica Foam (MCF for Intranasal Delivery of Paliperidone

    Directory of Open Access Journals (Sweden)

    Stavroula Nanaki

    2017-11-01

    Full Text Available In this study, mesocellular silica foam (MCF was used to encapsulate paliperidone, an antipsychotic drug used in patients suffering from bipolar disorder. MCF with the drug adsorbed was further encapsulated into poly(lactic acid (PLA and poly(lactide-co-glycolide (PLGA 75/25 w/w microspheres and these have been coated with thiolated chitosan. As found by TEM analysis, thiolated chitosan formed a thin layer on the polymeric microspheres’ surface and was used in order to enhance their mucoadhesiveness. These microspheres aimed at the intranasal delivery of paliperidone. The DSC and XRD studies showed that paliperidone was encapsulated in amorphous form inside the MCF silica and for this reason its dissolution profile was enhanced compared to the neat drug. In coated microspheres, thiolated chitosan reduced the initial burst effect of the paliperidone dissolution profile and in all cases sustained release formulations have been prepared. The release mechanism was also theoretically studied and three kinetic models were proposed and successfully fitted for a dissolution profile of prepared formulations to be found.

  4. Some Recent Advances in Transdermal Drug Delivery Systems ...

    African Journals Online (AJOL)

    Some Recent Advances in Transdermal Drug Delivery Systems. ... Advances in Transdermal Drug Delivery Systems. EC Ibezim, B Kabele-Toge, CO Anie, C Njoku. Abstract. Transdermal delivery systems are forms of drug delivery involving the dermis, as distinct from topical, oral or other forms of parenteral dosage forms.

  5. MODELING OF TARGETED DRUG DELIVERY PART II. MULTIPLE DRUG ADMINISTRATION

    Directory of Open Access Journals (Sweden)

    A. V. Zaborovskiy

    2017-01-01

    Full Text Available In oncology practice, despite significant advances in early cancer detection, surgery, radiotherapy, laser therapy, targeted therapy, etc., chemotherapy is unlikely to lose its relevance in the near future. In this context, the development of new antitumor agents is one of the most important problems of cancer research. In spite of the importance of searching for new compounds with antitumor activity, the possibilities of the “old” agents have not been fully exhausted. Targeted delivery of antitumor agents can give them a “second life”. When developing new targeted drugs and their further introduction into clinical practice, the change in their pharmacodynamics and pharmacokinetics plays a special role. The paper describes a pharmacokinetic model of the targeted drug delivery. The conditions under which it is meaningful to search for a delivery vehicle for the active substance were described. Primary screening of antitumor agents was undertaken to modify them for the targeted delivery based on underlying assumptions of the model.

  6. STRATEGIES AND PROSPECTS OF NASAL DRUG DELIVERY SYSTEMS

    OpenAIRE

    Gannu Praveen Kumar

    2012-01-01

    The recent advancement of nasal drug delivery systems has increased enormously and is gaining significant importance. Intranasal therapy has been an accepted form of treatment in the Ayurvedic system of Indian Medicine. The non-invasive delivery of nasal drug delivery systems made to exploit for the development of successful treatment. The advantages, disadvantages, mechanism of action and application of nasal drug delivery system in local delivery, systematic delivery, nasal vaccines and CNS...

  7. A facile degradable linkage for timed drug delivery

    International Nuclear Information System (INIS)

    Kenawy, E.; Abdel-Hay, F.I.; El-Newehy, M.H.; Ottenbrite, R.M.

    2005-01-01

    New drug delivery systems based on hydroxamic acid polymers were evaluated. The system support was the poly acryloyl chloride which was synthesized via free radical polymerization of acryloyl chloride in 1,4-dioxane, initiated with 2,2-azobisisobutyronitrile. Poly(N-alkyl substituted acrylamide) were synthesized in Poly(acryloyl chloride) was modified in two steps, the first is with N-hydroxysuccinimide to give the imide ester of poly(acryloyl). In the second step, the imide ester of poly(acryloyl) was reacted either with hydroxylamine or with (N-methyl hydroxylamine), respectively. The hydroxamic polymers were reacted with, the model drug, ketoprofen, in the presence of dicyclohexylcarbodiimide at -5 degree C. All products were characterized by elemental analysis, FTIR and 1 HNMR spectra. In vitro drug release study was performed at various ph and temperature to elucidate the influence of temperature and ph on the hydrolysis rate of the amido-ester bond that links the drug to the macromolecule. The amount of drug released from N-methyl hydroxamic acid polymers was higher than from hydroxamic acid polymers. All polymers showed higher drug release at 37 degree C than at room temperature (25 degree C) and at higher ph

  8. Specific drug delivery to the kidney

    NARCIS (Netherlands)

    Haas, M; Moolenaar, F; Meijer, DKF; de Zeeuw, D

    2002-01-01

    The mesangial cells of the glomerulus, the proximal tubular cells and the interstitial fibroblasts are the first choice targets for renal drug delivery since they play a pivotal role in many disease processes in the kidney. In the present review, only targeting to the proximal tubular cell is

  9. Immunological Risk of Injectable Drug Delivery Systems

    NARCIS (Netherlands)

    Jiskoot, W.; van Schie, R.M.F.; Carstens, M.G.; Schellekens, H.

    2009-01-01

    Injectable drug delivery systems (DDS) such as particulate carriers and water-soluble polymers are being used and developed for a wide variety of therapeutic applications. However, a number of immunological risks with serious clinical implications are associated with administration of DDS. These

  10. Biodegradable multiblock copolymers for drug delivery applications

    NARCIS (Netherlands)

    van Dijkhuizen-Radersma, Riemke

    2004-01-01

    With rapid advances in genomic research and biotechnology, an increasing number of pharmaceutical proteins and peptides become available for a variety of diseases. However, the efficient delivery of these drugs is hampered by their large size and (biological) instability. Consequently, to obtain a

  11. Carbon Nanotubes in Drug and Gene Delivery

    Science.gov (United States)

    Karimi, Mahdi; Ghasemi, Amir; Mirkiani, Soroush; Moosavi Basri, Seyed Masoud; Hamblin, Michael R.

    2017-10-01

    Recent important discoveries and developments in nanotechnology have had a remarkable and ever-increasing impact on many industries, especially materials science, pharmaceuticals, and biotechnology. Within this book, the authors describe different features of carbon nanotubes, survey the properties of both the multi-walled and single-walled varieties, and cover their applications in drug and gene delivery.

  12. Fluorescence optical imaging in anticancer drug delivery

    Czech Academy of Sciences Publication Activity Database

    Etrych, Tomáš; Lucas, H.; Janoušková, Olga; Chytil, Petr; Mueller, T.; Mäder, K.

    2016-01-01

    Roč. 226, 28 March (2016), s. 168-181 ISSN 0168-3659 R&D Projects: GA ČR(CZ) GA15-02986S; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : fluorescence imaging * drug delivery * theranostics Subject RIV: CD - Macromolecular Chemistry Impact factor: 7.786, year: 2016

  13. Nanocapsules: The Weapons for Novel Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Radhika Parasuramrajam

    2012-04-01

    Full Text Available Introduction: Nanocapsules, existing in miniscule size, range from 10 nm to 1000 nm. They consist of a liquid/solid core in which the drug is placed into a cavity, which is surrounded by a distinctive polymer membrane made up of natural or synthetic polymers. They have attracted great interest, because of the protective coating, which are usually pyrophoric and easily oxidized and delay the release of active ingredients. Methods: Various technical approaches are utilized for obtaining the nanocapsules; however, the methods of interfacial polymerization for monomer and the nano-deposition for preformed polymer are chiefly preferred. Most important characteristics in their preparation is particle size and size distribution which can be evaluated by using various techniques like X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, superconducting quantum interference device, multi angle laser light scattering and other spectroscopic techniques. Results: Nanocapsules possessing extremely high reproducibility have a broad range of life science applications. They may be applied in agrochemicals, genetic engineering, cosmetics, cleansing products, wastewater treatments, adhesive component applications, strategic delivery of the drug in tumors, nanocapsule bandages to fight infection, in radiotherapy and as liposomal nanocapsules in food science and agriculture. In addition, they can act as self-healing materials. Conclusion: The enhanced delivery of bioactive molecules through the targeted delivery by means of a nanocapsule opens numerous challenges and opportunities for the research and future development of novel improved therapies.

  14. [Drug delivery systems using nano-sized drug carriers].

    Science.gov (United States)

    Nakayama, Masamichi; Okano, Teruo

    2005-07-01

    Nanotechnology has attracted great attention all over the world in recent several years and has led to the establishment of the novel technical field of "nanomedicine" through collaboration with advanced medical technology. Particularly, site-specific drug targeting using particle drug carrier systems has made substantial progress and been actively developed. This review explains the essential factors (size and chemical character) of drug carriers to allow long circulation in the bloodstream avoiding the reticuloendothelial system, and shows the present status and future perspective of several types of nano-carrier systems (water-soluble polymer, liposome and polymeric micelle). We also introduce the novel concept of multi-targeting system (combination of two or more targeting methodologies) for ideal drug therapies.

  15. Fractional laser-assisted drug delivery

    DEFF Research Database (Denmark)

    Erlendsson, Andrés M; Doukas, Apostolos G; Farinelli, William A

    2016-01-01

    BACKGROUND AND OBJECTIVE: Ablative fractional laser (AFXL) is rapidly evolving as one of the foremost techniques for cutaneous drug delivery. While AFXL has effectively improved topical drug-induced clearance rates of actinic keratosis, treatment of basal cell carcinomas (BCCs) has been challenging......, potentially due to insufficient drug uptake in deeper skin layers. This study sought to investigate a standardized method to actively fill laser-generated channels by altering pressure, vacuum, and pressure (PVP), enquiring its effect on (i) relative filling of individual laser channels; (ii) cutaneous...

  16. Polymeric micelles with ionic cores containing biodegradable cross-links for delivery of chemotherapeutic agents.

    Science.gov (United States)

    Kim, Jong Oh; Sahay, Gaurav; Kabanov, Alexander V; Bronich, Tatiana K

    2010-04-12

    Novel functional polymeric nanocarriers with ionic cores containing biodegradable cross-links were developed for delivery of chemotherapeutic agents. Block ionomer complexes (BIC) of poly(ethylene oxide)-b-poly(methacylic acid) (PEO-b-PMA) and divalent metal cations (Ca(2+)) were utilized as templates. Disulfide bonds were introduced into the ionic cores by using cystamine as a biodegradable cross-linker. The resulting cross-linked micelles with disulfide bonds represented soft, hydrogel-like nanospheres and demonstrated a time-dependent degradation in the conditions mimicking the intracellular reducing environment. The ionic character of the cores allowed to achieve a very high level of doxorubicin (DOX) loading (50% w/w) into the cross-linked micelles. DOX-loaded degradable cross-linked micelles exhibited more potent cytotoxicity against human A2780 ovarian carcinoma cells as compared to micellar formulations without disulfide linkages. These novel biodegradable cross-linked micelles are expected to be attractive candidates for delivery of anticancer drugs.

  17. Formulation of two-layer dissolving polymeric microneedle patches for insulin transdermal delivery in diabetic mice.

    Science.gov (United States)

    Lee, I-Chi; Lin, Wei-Ming; Shu, Jwu-Ching; Tsai, Shau-Wei; Chen, Chih-Hao; Tsai, Meng-Tsan

    2017-01-01

    Dissolving microneedles (MNs) display high efficiency in delivering poorly permeable drugs and vaccines. Here, two-layer dissolving polymeric MN patches composed of gelatin and sodium carboxymethyl cellulose (CMC) were fabricated with a two-step casting and centrifuging process to localize the insulin in the needle and achieve efficient transdermal delivery of insulin. In vitro skin insertion capability was determined by staining with tissue-marking dye after insertion, and the real-time penetration depth was monitored using optical coherence tomography. Confocal microscopy images revealed that the rhodamine 6G and fluorescein isothiocyanate-labeled insulin (insulin-FITC) can gradually diffuse from the puncture sites to deeper tissue. Ex vivo drug-release profiles showed that 50% of the insulin was released and penetrated across the skin after 1 h, and the cumulative permeation reached 80% after 5 h. In vivo and pharmacodynamic studies were then conducted to estimate the feasibility of the administration of insulin-loaded dissolving MN patches on diabetic mice for glucose regulation. The total area above the glucose level versus time curve as an index of hypoglycemic effect was 128.4 ± 28.3 (% h) at 0.25 IU/kg. The relative pharmacologic availability and relative bioavailability (RBA) of insulin from MN patches were 95.6 and 85.7%, respectively. This study verified that the use of gelatin/CMC MN patches for insulin delivery achieved a satisfactory RBA compared to traditional hypodermic injection and presented a promising device to deliver poorly permeable protein drugs for diabetic therapy. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 84-93, 2017. © 2016 Wiley Periodicals, Inc.

  18. Oral transmucosal drug delivery for pediatric use.

    Science.gov (United States)

    Lam, Jenny K W; Xu, Yingying; Worsley, Alan; Wong, Ian C K

    2014-06-01

    The formulation of medicines for children remains a challenge. An ideal pediatric formulation must allow accurate dose administration and be in a dosage form that can be handled by the target age group. It is also important to consider the choices and the amount of excipients used in the formulation for this vulnerable age group. Although oral formulations are generally acceptable to most pediatric patients, they are not suitable for drugs with poor oral bioavailability or when a rapid clinical effect is required. In recent years, oral transmucosal delivery has emerged as an attractive route of administration for pediatric patients. With this route of administration, a drug is absorbed through the oral mucosa, therefore bypassing hepatic first pass metabolism and thus avoiding drug degradation or metabolism in the gastrointestinal tract. The high blood flow and relatively high permeability of the oral mucosa allow a quick onset of action to be achieved. It is a simple and non-invasive route of drug administration. However, there are several barriers that need to be overcome in the development of oral transmucosal products. This article aims to provide a comprehensive review of the current development of oral transmucosal delivery specifically for the pediatric population in order to achieve systemic drug delivery. The anatomical and physiological properties of the oral mucosa of infants and young children are carefully examined. The different dosage forms and formulation strategies that are suitable for young patients are discussed. © 2013.

  19. 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...

  20. Chitosan magnetic nanoparticles for drug delivery systems.

    Science.gov (United States)

    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.

  1. Nasal Delivery of High Molecular Weight Drugs

    Directory of Open Access Journals (Sweden)

    Erdal Cevher

    2009-09-01

    Full Text Available Nasal drug delivery may be used for either local or systemic effects. Low molecular weight drugs with are rapidly absorbed through nasal mucosa. The main reasons for this are the high permeability, fairly wide absorption area, porous and thin endothelial basement membrane of the nasal epithelium. Despite the many advantages of the nasal route, limitations such as the high molecular weight (HMW of drugs may impede drug absorption through the nasal mucosa. Recent studies have focused particularly on the nasal application of HMW therapeutic agents such as peptide-protein drugs and vaccines intended for systemic effects. Due to their hydrophilic structure, the nasal bioavailability of peptide and protein drugs is normally less than 1%. Besides their weak mucosal membrane permeability and enzymatic degradation in nasal mucosa, these drugs are rapidly cleared from the nasal cavity after administration because of mucociliary clearance. There are many approaches for increasing the residence time of drug formulations in the nasal cavity resulting in enhanced drug absorption. In this review article, nasal route and transport mechanisms across the nasal mucosa will be briefly presented. In the second part, current studies regarding the nasal application of macromolecular drugs and vaccines with nanoand micro-particulate carrier systems will be summarised.

  2. Self-Assembled Polymeric Micellar Nanoparticles as Nanocarriers for Poorly Soluble Anticancer Drug Ethaselen

    Directory of Open Access Journals (Sweden)

    Yang Zhuoli

    2009-01-01

    Full Text Available Abstract A series of monomethoxy poly(ethylene glycol-poly(lactide (mPEG-PLA diblock copolymers were synthesized, and mPEG-PLA micelle was fabricated and used as a nanocarrier for solubilization and delivery of a promising anticancer drug ethaselen. Ethaselen was efficiently encapsulated into the micelles by the dialysis method, and the solubility of ethaselen in water was remarkably increased up to 82 μg/mL before freeze-drying. The mean diameter of ethaselen-loaded micelles ranged from 51 to 98 nm with a narrow size distribution and depended on the length of PLA block. In vitro hemolysis study indicated that mPEG-PLA copolymers and ethaselen-loaded polymeric micelles had no hemolytic effect on the erythrocyte. The enhanced antitumor efficacy and reduced toxic effect of ethaselen-loaded polymeric micelle when compared with ethaselen-HP-β-CD inclusion were observed at the same dose in H22human liver cancer cell bearing mouse models. These suggested that mPEG-PLA polymeric micelle nanoparticles had great potential as nanocarriers for effective solubilization of poorly soluble ethaselen and further reducing side effects and toxicities of the drug.

  3. Design of new polymeric formulations for drug nanocarriers

    Science.gov (United States)

    Mattu, C.; Li, R.; Sartori, S.; Boffito, M.; Ramtoola, Z.; Ciardelli, G.

    2012-07-01

    In this work, novel strategies for the design and characterization of complex nanosized drug delivery systems for the release of different formulations were proposed and investigated. Natural or synthetic polymers, such as chitosan, poly (D,L lactide) (PLA) and proprietary polyesterurethanes, were used to prepare carriers for different applications in nanomedicine.

  4. Drug delivery and nanoparticles: Applications and hazards

    Directory of Open Access Journals (Sweden)

    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

  5. 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

  6. Multiscale modeling of transdermal drug delivery

    Science.gov (United States)

    Rim, Jee Eun

    2006-04-01

    This study addresses the modeling of transdermal diffusion of drugs, to better understand the permeation of molecules through the skin, and especially the stratum corneum, which forms the main permeation barrier of the skin. In transdermal delivery of systemic drugs, the drugs diffuse from a patch placed on the skin through the epidermis to the underlying blood vessels. The epidermis is the outermost layer of the skin and can be further divided into the stratum corneum (SC) and the viable epidermis layers. The SC consists of keratinous cells (corneocytes) embedded in the lipid multi-bilayers of the intercellular space. It is widely accepted that the barrier properties of the skin mostly arises from the ordered structure of the lipid bilayers. The diffusion path, at least for lipophilic molecules, seems to be mainly through the lipid bilayers. Despite the advantages of transdermal drug delivery compared to other drug delivery routes such as oral dosing and injections, the low percutaneous permeability of most compounds is a major difficulty in the wide application of transdermal drug delivery. In fact, many transdermal drug formulations include one or more permeation enhancers that increase the permeation of the drug significantly. During the last two decades, many researchers have studied percutaneous absorption of drugs both experimentally and theoretically. However, many are based on pharmacokinetic compartmental models, in which steady or pseudo-steady state conditions are assumed, with constant diffusivity and partitioning for single component systems. This study presents a framework for studying the multi-component diffusion of drugs coupled with enhancers through the skin by considering the microstructure of the stratum corneum (SC). A multiscale framework of modeling the transdermal diffusion of molecules is presented, by first calculating the microscopic diffusion coefficient in the lipid bilayers of the SC using molecular dynamics (MD). Then a

  7. 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

  8. Photopatternable Magnetic Hollowbots by Nd-Fe-B Nanocomposite for Potential Targeted Drug Delivery Applications

    Directory of Open Access Journals (Sweden)

    Hui Li

    2018-04-01

    Full Text Available In contrast to traditional drug administration, targeted drug delivery can prolong, localize, target and have a protected drug interaction with the diseased tissue. Drug delivery carriers, such as polymeric micelles, liposomes, dendrimers, nanotubes, and so on, are hard to scale-up, costly, and have short shelf life. Here we show the novel fabrication and characterization of photopatternable magnetic hollow microrobots that can potentially be utilized in microfluidics and drug delivery applications. These magnetic hollowbots can be fabricated using standard ultraviolet (UV lithography with low cost and easily accessible equipment, which results in them being easy to scale up, and inexpensive to fabricate. Contact-free actuation of freestanding magnetic hollowbots were demonstrated by using an applied 900 G external magnetic field to achieve the movement control in an aqueous environment. According to the movement clip, the average speed of the magnetic hollowbots was estimated to be 1.9 mm/s.

  9. Injectable In-Situ Gelling Controlled Release Drug Delivery System

    OpenAIRE

    Kulwant Singh; S. L. HariKumar

    2012-01-01

    The administration of poorly bioavailable drug through parenteral route is regarded the most efficient for drug delivery. Parenteral delivery provides rapid onset even for the drug with narrow therapeutic window, but to maintain the systemic drug level repeated installation are required which cause the patient discomfort. This can be overcome by designing the drug into a system, which control the drug release even through parenteral delivery, which improve patient compliance as well as pharma...

  10. A Comprehensive Review on: Transdermal drug delivery systems.

    OpenAIRE

    Kharat, Rekha; Bathe, Ritesh Suresh

    2016-01-01

    Transdermal drug delivery system was introduced to overcome the difficulties of drug delivery through oral route. Despite their relatively higher costs, transdermal delivery systems have proved advantageous for delivery of selected drugs, such as estrogens, testosterone, clonidine and nitro-glycerine. Transdermal delivery provides a leading edge over injectable and oral routes by increasing patient compliance and avoiding first pass metabolism respectively. Topical  administration  of  therap...

  11. Preparation of microspheres for slow release drug by radiation-induced suspension polymerization and their properties

    International Nuclear Information System (INIS)

    Yoshida, Masaru; Asano, Masaharu; Kaetsu, Isao

    1982-01-01

    The polymer microspheres containing drugs as drug delivery system were made by means of suspension-polymerization by radiation at low temperature by using glass-forming monomers which have stable supercooling properties and large polymerizability at low temperature. The particle distribution depended on the kind of monomer. It was found that the entrapping yield of drug in polymer microspheres increased with increasing viscosity of monomer and that the maximum value on the particle size distribution curve was also shifted to large particle diameter side. In the case of trimethylolpropane trimethacrylate monomer (43 cps), TMPT, the entrapping yield of drug reached 74% and the maximum value in particle size distribution curve appeared in the neighborhood of 105 to 210 mu m ranges. On the other hand, those values in neopentyl glycol dimethacrylate monomer (4 cps) were 12% in former and 44 -- 105 mu m in the latter. The release phenomenon of drugs from polymer microspheres was investigated. for example, the cumulative amount of mitomycin C (water soluble drug) released from TMPT polymer microsphere was about 90% after 30-day dissolution, while in the case of water-insoluble drug such as testosterone the amount of release was about 49% after 40-day dissolution. In all cases, the release rate is constant during the experimental period. Therefore, it was concluded that the release of drugs from polymer microspheres obtained in this study is possible over the long periods. (author)

  12. Stimuli-Responsive Liposomes for Controlled Drug Delivery

    KAUST Repository

    Li, Wengang

    2014-01-01

    Liposomes are promising drug delivery vesicles due to their biodegradibility, large volume and biocompatibility towards both hydrophilic and hydrophobic drugs. They suffer, however, from poor stability which limits their use in controlled delivery

  13. Advanced and controlled drug delivery systems in clinical disease management

    NARCIS (Netherlands)

    Brouwers, JRBJ

    1996-01-01

    Advanced and controlled drug delivery systems are important for clinical disease management. In this review the most important new systems which have reached clinical application are highlighted. Microbiologically controlled drug delivery is important for gastrointestinal diseases like ulcerative

  14. Microneedle Coating Techniques for Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Rita Haj-Ahmad

    2015-11-01

    Full Text Available Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates.

  15. Targeted Delivery of Protein Drugs by Nanocarriers

    Directory of Open Access Journals (Sweden)

    Antonella Battisti

    2010-03-01

    Full Text Available Recent advances in biotechnology demonstrate that peptides and proteins are the basis of a new generation of drugs. However, the transportation of protein drugs in the body is limited by their high molecular weight, which prevents the crossing of tissue barriers, and by their short lifetime due to immuno response and enzymatic degradation. Moreover, the ability to selectively deliver drugs to target organs, tissues or cells is a major challenge in the treatment of several human diseases, including cancer. Indeed, targeted delivery can be much more efficient than systemic application, while improving bioavailability and limiting undesirable side effects. This review describes how the use of targeted nanocarriers such as nanoparticles and liposomes can improve the pharmacokinetic properties of protein drugs, thus increasing their safety and maximizing the therapeutic effect.

  16. Polysaccharide-Based Micelles for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Nan Zhang

    2013-05-01

    Full Text Available Delivery of hydrophobic molecules and proteins has been an issue due to poor bioavailability following administration. Thus, micelle carrier systems are being investigated to improve drug solubility and stability. Due to problems with toxicity and immunogenicity, natural polysaccharides are being explored as substitutes for synthetic polymers in the development of new micelle systems. By grafting hydrophobic moieties to the polysaccharide backbone, self-assembled micelles can be readily formed in aqueous solution. Many polysaccharides also possess inherent bioactivity that can facilitate mucoadhesion, enhanced targeting of specific tissues, and a reduction in the inflammatory response. Furthermore, the hydrophilic nature of some polysaccharides can be exploited to enhance circulatory stability. This review will highlight the advantages of polysaccharide use in the development of drug delivery systems and will provide an overview of the polysaccharide-based micelles that have been developed to date.

  17. 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.

  18. Image-guided drug delivery: preclinical applications and clinical translation

    NARCIS (Netherlands)

    Ojha, Tarun; Rizzo, Larissa; Storm, Gerrit; Kiessling, Fabian; Lammers, Twan Gerardus Gertudis Maria

    2015-01-01

    Image-guided drug delivery refers to the combination of drug targeting and imaging. Preclinically, image-guided drug delivery can be used for several different purposes, including for monitoring biodistribution, target site accumulation, off-target localization, drug release and drug efficacy.

  19. Drug Delivery for Peripheral Nerve Regeneration

    Science.gov (United States)

    2015-11-01

    enhancement in dorsal root ganglion ( DRG ) cells with the released drug. In the first year of this 18 month project we have completed device fabrication of...the nerve guide conduit and drug delivery reservoir. We were able to release NGF at a concentration that enhancing DRG nerve growth in vitro. We next...KrF excimer laser system (Optec) and with diameters larger than 100μm using the VLS3.60 CO2 system (Universal Laser Systems )) (Figure 3). The laser

  20. Controlled Bioactive Molecules Delivery Strategies for Tendon and Ligament Tissue Engineering using Polymeric Nanofibers.

    Science.gov (United States)

    Hiong Teh, Thomas Kok; Hong Goh, James Cho; Toh, Siew Lok

    2015-01-01

    The interest in polymeric nanofibers has escalated over the past decade given its promise as tissue engineering scaffolds that can mimic the nanoscale structure of the native extracellular matrix. With functionalization of the polymeric nanofibers using bioactive molecules, localized signaling moieties can be established for the attached cells, to stimulate desired biological effects and direct cellular or tissue response. The inherently high surface area per unit mass of polymeric nanofibers can enhance cell adhesion, bioactive molecules loading and release efficiencies, and mass transfer properties. In this review article, the application of polymeric nanofibers for controlled bioactive molecules delivery will be discussed, with a focus on tendon and ligament tissue engineering. Various polymeric materials of different mechanical and degradation properties will be presented along with the nanofiber fabrication techniques explored. The bioactive molecules of interest for tendon and ligament tissue engineering, including growth factors and small molecules, will also be reviewed and compared in terms of their nanofiber incorporation strategies and release profiles. This article will also highlight and compare various innovative strategies to control the release of bioactive molecules spatiotemporally and explore an emerging tissue engineering strategy involving controlled multiple bioactive molecules sequential release. Finally, the review article concludes with challenges and future trends in the innovation and development of bioactive molecules delivery using polymeric nanofibers for tendon and ligament tissue engineering.

  1. 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.

  2. Advanced drug delivery approaches against periodontitis.

    Science.gov (United States)

    Joshi, Deeksha; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Periodontitis is an inflammatory disease of gums involving the degeneration of periodontal ligaments, creation of periodontal pocket and resorption of alveolar bone, resulting in the disruption of the support structure of teeth. According to WHO, 10-15% of the global population suffers from severe periodontitis. The disease results from the growth of a diverse microflora (especially anaerobes) in the pockets and release of toxins, enzymes and stimulation of body's immune response. Various local or systemic approaches were used for an effective treatment of periodontitis. Currently, controlled local drug delivery approach is more favorable as compared to systemic approach because it mainly focuses on improving the therapeutic outcomes by achieving factors like site-specific delivery, low dose requirement, bypass of first-pass metabolism, reduction in gastrointestinal side effects and decrease in dosing frequency. Overall it provides a safe and effective mode of treatment, which enhances patient compliance. Complete eradication of the organisms from the sites was not achieved by using various surgical and mechanical treatments. So a number of polymer-based delivery systems like fibers, films, chips, strips, microparticles, nanoparticles and nanofibers made from a variety of natural and synthetic materials have been successfully tested to deliver a variety of drugs. These systems are biocompatible and biodegradable, completely fill the pockets, and have strong retention on the target site due to excellent mucoadhesion properties. The review summarizes various available and recently developing targeted delivery devices for the treatment of periodontitis.

  3. 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...

  4. Glucantime drug delivery comparison between crosslinked membranes irradiation versus esterification

    International Nuclear Information System (INIS)

    Oliveira, Maria J.A.; Parra, Duclerc F.; Lugao, Ademar B.; Amato, Valdir S.

    2009-01-01

    Pentavalent Antimony (Glucantime) is the drug of choice for the treatment of Leishmaniasis. The disease is transmitted by the female bite of Phlebotomine sandflies. The sandflies inject the infective stage, metacyclic promastigotes, during blood meals. The protozoan parasite causes a spectrum of clinical diseases afflicting 12 million people worldwide. The use of hydrogels matrices for particular drug-release applications has been investigated with the synthesis of modified polymeric hydrogel of poly (vinyl alcohol) (PVAl), poly (N-viny-2- pyrrolidone) (PVP) and poly (ethylene glycol). They were processed using gamma radiation from Cobalt-60 source at 25 kGy dose. The characterization of the hydrogels was conducted and toxicity was evaluated. The dried hydrogel was analyzed for differential scanning calorimetry (DSC), thermogravimetry (TGA), swelling and gel content determinations. The membranes have no toxicity and gel content has revealed the crosslink degree. The chemical crosslinking depends on the acid concentration. Increase of the acid concentration increases the gel content, the thermal stability of the PVAl component and decreases the swelling capacity. The thermal stability of irradiated membranes is decreased in the presence of plasticizer. In contrast to ionizing radiation membranes described in the literature and formulated with PVAl/PEG, our new membranes composed by PVAl/PVP/PEG are more flexible and presents higher swelling capacity. The drug was immobilized in the hydrogels structures and the glucantime drug delivery was determined. (author)

  5. Glucantime drug delivery comparison between crosslinked membranes irradiation versus esterification

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Maria J.A.; Parra, Duclerc F.; Lugao, Ademar B., E-mail: mariajhho@yahoo.com.b, E-mail: dfparra@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil). Centro de Quimica e Meio Ambiente (CQMA); Amato, Valdir S. [Hospital das Clinicas (HC/USP), Sao Paulo, SP (Brazil). Div. de Clinica de Molestias Infecciosas e Parasitarias

    2009-07-01

    Pentavalent Antimony (Glucantime) is the drug of choice for the treatment of Leishmaniasis. The disease is transmitted by the female bite of Phlebotomine sandflies. The sandflies inject the infective stage, metacyclic promastigotes, during blood meals. The protozoan parasite causes a spectrum of clinical diseases afflicting 12 million people worldwide. The use of hydrogels matrices for particular drug-release applications has been investigated with the synthesis of modified polymeric hydrogel of poly (vinyl alcohol) (PVAl), poly (N-viny-2- pyrrolidone) (PVP) and poly (ethylene glycol). They were processed using gamma radiation from Cobalt-60 source at 25 kGy dose. The characterization of the hydrogels was conducted and toxicity was evaluated. The dried hydrogel was analyzed for differential scanning calorimetry (DSC), thermogravimetry (TGA), swelling and gel content determinations. The membranes have no toxicity and gel content has revealed the crosslink degree. The chemical crosslinking depends on the acid concentration. Increase of the acid concentration increases the gel content, the thermal stability of the PVAl component and decreases the swelling capacity. The thermal stability of irradiated membranes is decreased in the presence of plasticizer. In contrast to ionizing radiation membranes described in the literature and formulated with PVAl/PEG, our new membranes composed by PVAl/PVP/PEG are more flexible and presents higher swelling capacity. The drug was immobilized in the hydrogels structures and the glucantime drug delivery was determined. (author)

  6. 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.

  7. Drug Delivery to the Ischemic Brain

    Science.gov (United States)

    Thompson, Brandon J.; Ronaldson, Patrick T.

    2014-01-01

    Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

  8. Drug Delivery to CNS: Challenges and Opportunities with Emphasis on Biomaterials Based Drug Delivery Strategies.

    Science.gov (United States)

    Khambhla, Ekta; Shah, Viral; Baviskar, Kalpesh

    2016-01-01

    The current epoch has witnessed a lifestyle impregnated with stress, which is a major cause of several neurological disorders. High morbidity and mortality rate due to neurological diseases and disorders have generated a huge social impact. Despite voluminous research, patients suffering from fatal and/or debilitating CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy, Parkinson's, migraine and multiple sclerosis outnumbered those suffering from systemic cancer or heart diseases. The brain being a highly sensitive neuronal organ, has evolved with vasculature barriers, which regulates the efflux and influx of substances to CNS. Treatment of CNS diseases/disorders is challenging because of physiologic, metabolic and biochemical obstacles created by these barriers which comprise mainly of BBB and BCFB. The inability of achieving therapeutically active concentration has become the bottleneck level difficulty, hampering the therapeutic efficiency of several promising drug candidates for CNS related disorders. Parallel maturation of an effective CNS drug delivery strategy with CNS drug discovery is the need of the hour. Recently, the focus of the pharmaceutical community has aggravated in the direction of developing novel and more efficient drug delivery systems, giving the potential of more effective and safer CNS therapies. The present review outlines several hurdles in drug delivery to the CNS along with ideal physicochemical properties desired in drug substance/formulation for CNS delivery. The review also focuses on different conventional and novel strategies for drug delivery to the CNS. The article also assesses and emphasizes on possible benefits of biomaterial based formulations for drug delivery to the CNS.

  9. Enhanced cytotoxicity of anticancer drug delivered by novel nanoscale polymeric carrier

    Science.gov (United States)

    Stoika, R.; Boiko, N.; Senkiv, Y.; Shlyakhtina, Y.; Panchuk, R.; Finiuk, N.; Filyak, Y.; Bilyy, R.; Kit, Y.; Skorohyd, N.; Klyuchivska, O.; Zaichenko, A.; Mitina, N.; Ryabceva, A.

    2013-04-01

    We compared in vitro action of highly toxic anticancer drug doxorubicin under its delivery to the mammalian tumor cells in free form and after encapsulation in novel bio-functionalized nanoscale polymeric carrier. Such encapsulation was found to enhance significantly drug uptake by the targeted cells, as well as its cytotoxic action. 10 times higher cytotoxicity of the carrier-immobilized doxorubicin comparing to its free form was demonstrated by direct cell counting, and 5 times higher cytotoxicity of encapsulated doxorubicin was shown by FACS analysis. The polymeric carrier itself did not possess significant toxicity in vitro or in vivo (laboratory mice). The carrier protected against negative side effects of doxorubicin in mice with experimental NK/Ly lymphoma. The life duration of tumor-bearing animals treated with doxorubicin-carrier complex was significantly longer than life duration in animals treated with free doxorubicin. Besides, the effective treatment dose of the carrier-delivered doxorubicin in tumor-bearing mice was 10 times lower than such dose of free doxorubicin. Thus, novel nanoscale polymers possess high potential as drug carrier.

  10. Enhanced cytotoxicity of anticancer drug delivered by novel nanoscale polymeric carrier

    International Nuclear Information System (INIS)

    Stoika, R; Boiko, N; Panchuk, R; Filyak, Y; Senkiv, Y; Finiuk, N; Shlyakhtina, Y; Bilyy, R; Kit, Y; Skorohyd, N; Klyuchivska, O; Zaichenko, A; Mitina, N; Ryabceva, A

    2013-01-01

    We compared in vitro action of highly toxic anticancer drug doxorubicin under its delivery to the mammalian tumor cells in free form and after encapsulation in novel bio-functionalized nanoscale polymeric carrier. Such encapsulation was found to enhance significantly drug uptake by the targeted cells, as well as its cytotoxic action. 10 times higher cytotoxicity of the carrier-immobilized doxorubicin comparing to its free form was demonstrated by direct cell counting, and 5 times higher cytotoxicity of encapsulated doxorubicin was shown by FACS analysis. The polymeric carrier itself did not possess significant toxicity in vitro or in vivo (laboratory mice). The carrier protected against negative side effects of doxorubicin in mice with experimental NK/Ly lymphoma. The life duration of tumor-bearing animals treated with doxorubicin-carrier complex was significantly longer than life duration in animals treated with free doxorubicin. Besides, the effective treatment dose of the carrier-delivered doxorubicin in tumor-bearing mice was 10 times lower than such dose of free doxorubicin. Thus, novel nanoscale polymers possess high potential as drug carrier.

  11. Silk Electrogel Based Gastroretentive Drug Delivery System

    Science.gov (United States)

    Wang, Qianrui

    Gastric cancer has become a global pandemic and there is imperative to develop efficient therapies. Oral dosing strategy is the preferred route to deliver drugs for treating the disease. Recent studies suggested silk electro hydrogel, which is pH sensitive and reversible, has potential as a vehicle to deliver the drug in the stomach environment. The aim of this study is to establish in vitro electrogelation e-gel based silk gel as a gastroretentive drug delivery system. We successfully extended the duration of silk e-gel in artificial gastric juice by mixing silk solution with glycerol at different ratios before the electrogelation. Structural analysis indicated the extended duration was due to the change of beta sheet content. The glycerol mixed silk e-gel had good doxorubicin loading capability and could release doxorubicin in a sustained-release profile. Doxorubicin loaded silk e-gels were applied to human gastric cancer cells. Significant cell viability decrease was observed. We believe that with further characterization as well as functional analysis, the silk e-gel system has the potential to become an effective vehicle for gastric drug delivery applications.

  12. 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.

  13. Drug delivery system design and development for boron neutron capture therapy on cancer treatment

    International Nuclear Information System (INIS)

    Sherlock Huang, Lin-Chiang; Hsieh, Wen-Yuan; Chen, Jiun-Yu; Huang, Su-Chin; Chen, Jen-Kun; Hsu, Ming-Hua

    2014-01-01

    We have already synthesized a boron-containing polymeric micellar drug delivery system for boron neutron capture therapy (BNCT). The synthesized diblock copolymer, boron-terminated copolymers (Bpin-PLA-PEOz), consisted of biodegradable poly(D,L-lactide) (PLA) block and water-soluble polyelectrolyte poly(2-ethyl-2-oxazoline) (PEOz) block, and a cap of pinacol boronate ester (Bpin). In this study, we have demonstrated that synthesized Bpin-PLA-PEOz micelle has great potential to be boron drug delivery system with preliminary evaluation of biocompatibility and boron content. - Highlights: • Herein, we have synthesized boron-modified diblock copolymer. • Bpin-PLA-PEOz, which will be served as new boron containing vehicle for transporting the boron drug. • This boron containing Bpin-PLA-PEOz micelle was low toxicity can be applied to drug delivery

  14. Transdermal microneedles for drug delivery applications

    International Nuclear Information System (INIS)

    Teo, Ai Ling; Shearwood, Christopher; Ng, Kian Chye; Lu Jia; Moochhala, Shabbir

    2006-01-01

    Transdermal drug delivery (TDD) has many advantages, the main one being the ability to maintain the prolonged release of drugs to attain optimal blood concentrations. Unfortunately, nature has provided a very effective protective barrier, the stratum corneum (sc), which limits TDD to certain types of drugs with specific properties. In order to enhance TDD, the idea of using microneedles to painlessly penetrate the sc barrier has previously been proposed. In this paper, we will review the different microneedles that are currently being developed as well as our own efforts in this area. Based on our experiences, we will offer our view on the key parameters for effective transdermal microneedle design as well as future directions in this area

  15. Transdermal microneedles for drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Teo, Ai Ling [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Shearwood, Christopher [School of Mechanical and Aerospace Engineering, 50 Nanyang Avenue, Singapore 639798 (Singapore); Ng, Kian Chye [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Lu Jia [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Moochhala, Shabbir [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore)]. E-mail: mshabbir@dso.org.sg

    2006-07-25

    Transdermal drug delivery (TDD) has many advantages, the main one being the ability to maintain the prolonged release of drugs to attain optimal blood concentrations. Unfortunately, nature has provided a very effective protective barrier, the stratum corneum (sc), which limits TDD to certain types of drugs with specific properties. In order to enhance TDD, the idea of using microneedles to painlessly penetrate the sc barrier has previously been proposed. In this paper, we will review the different microneedles that are currently being developed as well as our own efforts in this area. Based on our experiences, we will offer our view on the key parameters for effective transdermal microneedle design as well as future directions in this area.

  16. Conductive polymer nanotube patch for fast and controlled in vivo transdermal drug delivery

    Science.gov (United States)

    Nguyen, Thao M.

    , while the control showed no visible drugs at the same depth. Most importantly, it was determined that the delivery of drugs into the blood stream was stable within 20 minutes. The functionalization of CP was also studied in order to enhance the properties and drug loading capabilities of the polymers. The co-polymerization of poly(3,4-(2-methylene)propylenedioxythiophene) (PMProDot) with polystyrene (PS) and polyvinylcarbazole (PVK) through the highly reactive methylene group was achieved. The modified PMProDot nanotubes demonstrated response times that were two times faster than without modification. The modification of PEDOT nanotubes with polydopamine, a biocompatible polymer, was also investigated and achieved. In depth characterization of functionalized CP demonstrate the ability to fine tune the properties of the polymer in order to achieve the required therapeutic drug release profile.

  17. Inhalation drug delivery devices: technology update

    Directory of Open Access Journals (Sweden)

    Ibrahim M

    2015-02-01

    Full Text Available Mariam Ibrahim, Rahul Verma, Lucila Garcia-ContrerasDepartment of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAbstract: The pulmonary route of administration has proven to be effective in local and systemic delivery of miscellaneous drugs and biopharmaceuticals to treat pulmonary and non-pulmonary diseases. A successful pulmonary administration requires a harmonic interaction between the drug formulation, the inhaler device, and the patient. However, the biggest single problem that accounts for the lack of desired effect or adverse outcomes is the incorrect use of the device due to lack of training in how to use the device or how to coordinate actuation and aerosol inhalation. This review summarizes the structural and mechanical features of aerosol delivery devices with respect to mechanisms of aerosol generation, their use with different formulations, and their advantages and limitations. A technological update of the current state-of-the-art designs proposed to overcome current challenges of existing devices is also provided.Keywords: pulmonary delivery, asthma, nebulizers, metered dose inhaler, dry powder inhaler

  18. Multiscale benchmarking of drug delivery vectors.

    Science.gov (United States)

    Summers, Huw D; Ware, Matthew J; Majithia, Ravish; Meissner, Kenith E; Godin, Biana; Rees, Paul

    2016-10-01

    Cross-system comparisons of drug delivery vectors are essential to ensure optimal design. An in-vitro experimental protocol is presented that separates the role of the delivery vector from that of its cargo in determining the cell response, thus allowing quantitative comparison of different systems. The technique is validated through benchmarking of the dose-response of human fibroblast cells exposed to the cationic molecule, polyethylene imine (PEI); delivered as a free molecule and as a cargo on the surface of CdSe nanoparticles and Silica microparticles. The exposure metrics are converted to a delivered dose with the transport properties of the different scale systems characterized by a delivery time, τ. The benchmarking highlights an agglomeration of the free PEI molecules into micron sized clusters and identifies the metric determining cell death as the total number of PEI molecules presented to cells, determined by the delivery vector dose and the surface density of the cargo. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Drug accumulation by means of noninvasive magnetic drug delivery system

    International Nuclear Information System (INIS)

    Chuzawa, M.; Mishima, F.; Akiyama, Y.; Nishijima, S.

    2011-01-01

    The medication is one of the most general treatment methods, but drugs diffuse in the normal tissues other than the target part by the blood circulation. Therefore, side effect in the medication, particularly for a drug with strong effect such as anti-cancer drug, are a serious issue. Drug Delivery System (DDS) which accumulates the drug locally in the human body is one of the techniques to solve the side-effects. Magnetic Drug Delivery System (MDDS) is one of the active DDSs, which uses the magnetic force. The objective of this study is to accumulate the ferromagnetic drugs noninvasively in the deep part of the body by using MDDS. It is necessary to generate high magnetic field and magnetic gradient at the target part to reduce the side-effects to the tissues with no diseases. The biomimetic model was composed, which consists of multiple model organs connected with diverged blood vessel model. The arrangement of magnetic field was examined to accumulate ferromagnetic drug particles in the target model organ by using a superconducting bulk magnet which can generate high magnetic fields. The arrangement of magnet was designed to generate high and stable magnetic field at the target model organ. The accumulation experiment of ferromagnetic particles has been conducted. In this study, rotating HTS bulk magnet around the axis of blood vessels by centering on the target part was suggested, and the model experiment for magnet rotation was conducted. As a result, the accumulation of the ferromagnetic particles to the target model organ in the deep part was confirmed.

  20. Drug-Induced Morphology Switch in Drug Delivery Systems Based on Poly(2-oxazoline)s

    Science.gov (United States)

    2015-01-01

    Defined aggregates of polymers such as polymeric micelles are of great importance in the development of pharmaceutical formulations. The amount of drug that can be formulated by a drug delivery system is an important issue, and most drug delivery systems suffer from their relatively low drug-loading capacity. However, as the loading capacities increase, i.e., promoted by good drug–polymer interactions, the drug may affect the morphology and stability of the micellar system. We investigated this effect in a prominent system with very high capacity for hydrophobic drugs and found extraordinary stability as well as a profound morphology change upon incorporation of paclitaxel into micelles of amphiphilic ABA poly(2-oxazoline) triblock copolymers. The hydrophilic blocks A comprised poly(2-methyl-2-oxazoline), while the middle blocks B were either just barely hydrophobic poly(2-n-butyl-2-oxazoline) or highly hydrophobic poly(2-n-nonyl-2-oxazoline). The aggregation behavior of both polymers and their formulations with varying paclitaxel contents were investigated by means of dynamic light scattering, atomic force microscopy, (cryogenic) transmission electron microscopy, and small-angle neutron scattering. While without drug, wormlike micelles were present, after incorporation of small amounts of drugs only spherical morphologies remained. Furthermore, the much more hydrophobic poly(2-n-nonyl-2-oxazoline)-containing triblock copolymer exhibited only half the capacity for paclitaxel than the poly(2-n-butyl-2-oxazoline)-containing copolymer along with a lower stability. In the latter, contents of paclitaxel of 8 wt % or higher resulted in a raspberry-like micellar core. PMID:24548260

  1. Recent advances in chitosan-based nanoparticulate pulmonary drug delivery

    Science.gov (United States)

    Islam, Nazrul; Ferro, Vito

    2016-07-01

    The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed.

  2. Pectin-based colon-specific drug delivery

    OpenAIRE

    Shailendra Shukla; Deepak Jain; Kavita Verma; Shiddarth Verma

    2011-01-01

    Colon-specific drug delivery have a great importance in the delivery of drugs for the treatment of local colonic, as well as systemic diseases like Crohn′s disease, ulcerative colitis, colorectal cancer, amoebiasis, asthma, arthritis and inflammation which can be achieved by targeted delivery of drug to colon. Specific systemic absorption in the colon gave interesting possibilities for the delivery of protein and peptides. It contains relatively less proteolytic enzyme activities in the colon...

  3. Fluorescence optical imaging in anticancer drug delivery.

    Science.gov (United States)

    Etrych, Tomáš; Lucas, Henrike; Janoušková, Olga; Chytil, Petr; Mueller, Thomas; Mäder, Karsten

    2016-03-28

    In the past several decades, nanosized drug delivery systems with various targeting functions and controlled drug release capabilities inside targeted tissues or cells have been intensively studied. Understanding their pharmacokinetic properties is crucial for the successful transition of this research into clinical practice. Among others, fluorescence imaging has become one of the most commonly used imaging tools in pre-clinical research. The development of increasing numbers of suitable fluorescent dyes excitable in the visible to near-infrared wavelengths of the spectrum has significantly expanded the applicability of fluorescence imaging. This paper focuses on the potential applications and limitations of non-invasive imaging techniques in the field of drug delivery, especially in anticancer therapy. Fluorescent imaging at both the cellular and systemic levels is discussed in detail. Additionally, we explore the possibility for simultaneous treatment and imaging using theranostics and combinations of different imaging techniques, e.g., fluorescence imaging with computed tomography. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. 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

  5. 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.

  6. Advanced progress of microencapsulation technologies: in vivo and in vitro models for studying oral and transdermal drug deliveries.

    Science.gov (United States)

    Lam, P L; Gambari, R

    2014-03-28

    This review provides an overall discussion of microencapsulation systems for both oral and transdermal drug deliveries. Clinically, many drugs, especially proteins and peptides, are susceptible to the gastrointestinal tract and the first-pass metabolism after oral administration while some drugs exhibit low skin permeability through transdermal delivery route. Medicated microcapsules as oral and transdermal drug delivery vehicles are believed to offer an extended drug effect at a relatively low dose and provide a better patient compliance. The polymeric microcapsules can be produced by different microencapsulation methods and the drug microencapsulation technology provides the quality preservation for drug stabilization. The release of the entrapped drug is controlled and prolonged for specific usages. Some recent studies have focused on the evaluation of drug containing microcapsules on potential biological and therapeutic applications. For the oral delivery, in vivo animal models were used for evaluating possible treatment effects of drug containing microcapsules. For the transdermal drug delivery, skin delivery models were introduced to investigate the potential skin delivery of medicated microcapsules. Finally, the challenges and limitations of drug microencapsulation in real life are discussed and the commercially available drug formulations using microencapsulation technology for oral and transdermal applications are shown. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Advancement in integrin facilitated drug delivery.

    Science.gov (United States)

    Arosio, Daniela; Casagrande, Cesare

    2016-02-01

    The research of integrin-targeted anticancer agents has recorded important advancements in ingenious design of delivery systems, based either on the prodrug approach, or on nanoparticle carriers, but for now, none of these has reached a clinical stage of development. Past work in this area has been extensively reviewed by us and others. Thus, the purpose and scope of the present review is to survey the advancement reported in the last 3years, with focus on innovative delivery systems that appear to afford openings for future developments. These systems exploit the labelling with conventional and novel integrin ligands for targeting the interface of cancer cells and of endothelial cells involved in cancer angiogenesis, with the proteins of the extracellular matrix, in the circulation, in tissues, and in tumour stroma, as the site of progression and metastatic evolution of the disease. Furthermore, these systems implement the expertise in the development of nanomedicines to the purpose of achieving preferential biodistribution and uptake in cancer tissues, internalisation in cancer cells, and release of the transported drugs at intracellular sites. The assessment of the value of controlling these factors, and their combination, for future developments requires support of biological testing in appropriate mechanistic models, but also imperatively demand confirmation in therapeutically relevant in vivo models for biodistribution, efficacy, and lack of off-target effects. Thus, among many studies, we have tried to point out the results supported by relevant in vivo studies, and we have emphasised in specific sections those addressing the medical needs of drug delivery to brain tumours, as well as the delivery of oligonucleotides modulating gene-dependent pathological mechanism. The latter could constitute the basis of a promising third branch in the therapeutic armamentarium against cancer, in addition to antibody-based agents and to cytotoxic agents. Copyright © 2015

  8. Adenovirus dodecahedron, as a drug delivery vector.

    Directory of Open Access Journals (Sweden)

    Monika Zochowska

    Full Text Available BACKGROUND: Bleomycin (BLM is an anticancer antibiotic used in many cancer regimens. Its utility is limited by systemic toxicity and dose-dependent pneumonitis able to progress to lung fibrosis. The latter can affect up to nearly 50% of the total patient population, out of which 3% will die. We propose to improve BLM delivery by tethering it to an efficient delivery vector. Adenovirus (Ad dodecahedron base (DB is a particulate vector composed of 12 copies of a pentameric viral protein responsible for virus penetration. The vector efficiently penetrates the plasma membrane, is liberated in the cytoplasm and has a propensity to concentrate around the nucleus; up to 300000 particles can be observed in one cell in vitro. PRINCIPAL FINDINGS: Dodecahedron (Dd structure is preserved at up to about 50 degrees C at pH 7-8 and during dialysis, freezing and drying in the speed-vac in the presence of 150 mM ammonium sulfate, as well as during lyophilization in the presence of cryoprotectants. The vector is also stable in human serum for 2 h at 37 degrees C. We prepared a Dd-BLM conjugate which upon penetration induced death of transformed cells. Similarly to free bleomycin, Dd-BLM caused dsDNA breaks. Significantly, effective cytotoxic concentration of BLM delivered with Dd was 100 times lower than that of free bleomycin. CONCLUSIONS/SIGNIFICANCE: Stability studies show that Dds can be conveniently stored and transported, and can potentially be used for therapeutic purposes under various climates. Successful BLM delivery by Ad Dds demonstrates that the use of virus like particle (VLP results in significantly improved drug bioavailability. These experiments open new vistas for delivery of non-permeant labile drugs.

  9. Engineering bioceramic microstructure for customized drug delivery

    Science.gov (United States)

    Pacheco Gomez, Hernando Jose

    One of the most efficient approaches to treat cancer and infection is to use biomaterials as a drug delivery system (DDS). The goal is for the material to provide a sustained release of therapeutic drug dose locally to target the ill tissue without affecting other organs. Silica Calcium Phosphate nano composite (SCPC) is a drug delivery platform that successfully demonstrated the ability to bind and release several therapeutics including antibiotics, anticancer drugs, and growth factors. The aim of the present work is to analyze the role of SCPC microstructure on drug binding and release kinetics. The main crystalline phases of SCPC are alpha-cristobalite (SiO2, Cris) and beta-rhenanite (NaCaPO4, Rhe); therefore, these two phases were prepared and characterized separately. Structural and compositional features of Cris, Rhe and SCPC bioceramics demonstrated a significant influence on the loading capacity and release kinetics profile of Vancomycin (Vanc) and Cisplatin (Cis). Fourier Transform Infrared (FTIR) spectroscopy analyses demonstrated that the P-O functional group in Rhe and SCPC has high affinity to the (C=O and N-H) of Vanc and (N-H and O-H) of Cis. By contrast, a weak chemical interaction between the Si-O functional group in Cris and SCPC and the two drugs was observed. Vanc loading per unit surface area increased in the order 8.00 microg Vanc/m2 for Rhe > 4.49 microg Vanc /m2 for SCPC>3.01 microg Vanc /m2 for Cris (pproducts and the released drug did not cause measurable negative effects on the bioactivity of the tested drugs. The therapeutic effects of the SCPC-Cis hybrid were evaluated using a rat model of hepatocellular carcinoma (HCC). Animals were treated by either systemic cisplatin injection (sCis), or with SCPC-Cis hybrid placed adjacent (ADJ) to, or within (IT), the tumor. Five days after implantation 50-55% of the total cisplatin loaded was released from the SCPC-Cis hybrids resulting in an approximately 50% decrease in tumor volume compared to

  10. Drug delivery from the oral cavity: a focus on mucoadhesive buccal drug delivery systems.

    Science.gov (United States)

    Shinkar, Dattatraya Manohar; Dhake, Avinash Sridhar; Setty, Chitral Mallikarjuna

    2012-01-01

    Since the early 1980s the concept of mucoadhesion has gained considerable interest in pharmaceutical technology. The various advantages associated with these systems made buccal drug delivery as a novel route of drug administration. It prolongs the residence time of the dosage form at the site of application. These systems remain in close contact with the absorption tissue, the mucous membrane, and thus contribute to improved and/or better therapeutic performance of the drug and of both local and systemic effects. This review highlights the anatomy and structure of oral mucosa, mechanism and theories of mucoadhesion, factors affecting mucoadhesion, characteristics and properties of desired mucoadhesive polymers, various types of dosage forms, and general considerations in design of mucoadhesive buccal dosage forms, permeation enhancers, and evaluation methods. Over the past few decades the mucoadhesive buccal drug delivery system has received a great deal of attention to develop mucoadhesive dosage forms to enable the prolonged retention at the site of action, providing a controlled release of drug for improved therapeutic outcome. Mucoadhesive drug delivery gives facility to include a permeation enhancer/enzyme inhibitor or pHmodifier in the formulation and versatility in designing as multidirectional or unidirectional release systems for local and systemic action. Local delivery to tissues of the oral cavity has a number of applications, including treatment of local conditions such as periodontal disease, bacterial and fungal infections, and aphthous stomatitis and vesiculo bullous diseases. For the treatment of chronic diseases, the mucoadhesive buccal drug delivery system allows easily accessibility and is generally well-accepted for administeringdrugs by systemic action.

  11. Impact of nanotechnology on drug delivery.

    Science.gov (United States)

    Farokhzad, Omid C; Langer, Robert

    2009-01-27

    Nanotechnology is the engineering and manufacturing of materials at the atomic and molecular scale. In its strictest definition from the National Nanotechnology Initiative, nanotechnology refers to structures roughly in the 1-100 nm size regime in at least one dimension. Despite this size restriction, nanotechnology commonly refers to structures that are up to several hundred nanometers in size and that are developed by top-down or bottom-up engineering of individual components. Herein, we focus on the application of nanotechnology to drug delivery and highlight several areas of opportunity where current and emerging nanotechnologies could enable entirely novel classes of therapeutics.

  12. A review on target drug delivery: magnetic microspheres

    OpenAIRE

    Amit Chandna; Deepa Batra; Satinder Kakar; Ramandeep Singh

    2013-01-01

    Novel drug delivery system aims to deliver the drug at a rate directed by the needs of the body during the period of treatment, and target the active entity to the site of action. A number of novel drug delivery systems have emerged encompassing various routes of administration, to achieve controlled and targeted drug delivery, magnetic micro carriers being one of them. Magnetic microsphere is newer approach in pharmaceutical field. Magnetic microspheres as an alternative to traditional ra...

  13. Broadly Applicable Nanowafer Drug Delivery System for Treating Eye Injuries

    Science.gov (United States)

    2015-09-01

    Systems in Systemic , Dermal, Transdermal , and Ocular Drug Delivery . Crit. Rev. Ther. Drug 2008, 25, 545–584. 14. Choy, Y. B.; Park, J.-H.; McCarey, B...AWARD NUMBER: W81XWH-13-1-0146 TITLE: Broadly Applicable Nanowafer Drug Delivery System for Treating Eye Injuries PRINCIPAL INVESTIGATOR: Dr...Broadly Applicable Nanowafer Drug Delivery System for Treating Eye Injuries” 5b. GRANT NUMBER W81XWH-13-1-0146 5c. PROGRAM ELEMENT NUMBER 6

  14. Bioengineered microparticles for controlled drug delivery to the lungs

    OpenAIRE

    Sivadas, Neeraj

    2010-01-01

    Traditional formulations for pulmonary drug delivery mainly focused on two approaches: (i) Dissolving or suspending the drug in a solvent or propellant to produce liquid aerosols or (ii) Blending drug particulates with dry carrier particles typically composed of sugars. Although effective for localised delivery of small drug molecules, these methods did not meet the complex formulation and delivery challenges posed by the newer biotechnology-derived medicines. One of the many avenues being ex...

  15. Recent Progress in Functional Micellar Carriers with Intrinsic Therapeutic Activities for Anticancer Drug Delivery.

    Science.gov (United States)

    Qu, Ying; Chu, BingYang; Shi, Kun; Peng, JinRong; Qian, ZhiYong

    2017-12-01

    Polymeric micelles have presented superior delivery properties for poorly water-soluble chemotherapeutic agents. However, it remains discouraging that there may be some additional short or long-term toxicities caused by the metabolites of high quantities of carriers. If carriers had simultaneous therapeutic effects with the drug, these issues would not be a concern. For this, carriers not only simply act as drug carriers, but also exert an intrinsic therapeutic effect as a therapeutic agent. The functional micellar carriers would be beneficial to maximize the anticancer effect, overcome the drug resistance and reduce the systemic toxicity. In this review, we aim to summarize the recent progress on the development of functional micellar carriers with intrinsic anticancer activities for the delivery of anticancer drugs. This review focuses on the design strategies, properties of carriers and the drug loading behavior. In addition, the combinational therapeutic effects between carriers and chemotherapeutic agents are also discussed.

  16. Advanced Drug-Delivery Systems of Curcumin for Cancer Chemoprevention

    Science.gov (United States)

    Bansal, Shyam S.; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V.; Gupta, Ramesh C.

    2011-01-01

    From ancient times, chemopreventive agents have been used to treat/prevent several diseases, including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, anti-oxidant, anti-proliferative, anti-carcinogenic, and anti-angiogenic activity in various cell culture and some animal studies. Research over the past four decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell-culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been demonstrated to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician’s armamentarium. PMID:21546540

  17. Updates on smart polymeric carrier systems for protein delivery.

    Science.gov (United States)

    El-Sherbiny, Ibrahim; Khalil, Islam; Ali, Isra; Yacoub, Magdi

    2017-10-01

    Smart materials are those materials that are responsive to chemical (organic molecules, chemical agents or specific agents), biochemical (protein, enzymes, growth factors, substrates or ligands), physical (electric field, magnetic field, temperature, pH, ionic strength or radiation) or mechanical (pressure or mechanical stress) signals. These responsive materials interact with the stimuli by changing their properties or conformational structures in a predictable manner. Recently, smart polymers have been utilized in various biomedical applications. Particularly, they have been used as a platform to synthesize stimuli-responsive systems that could deliver therapeutics to a specific site for a specific period with minimal adverse effects. For instance, stimuli-responsive polymers-based systems have been recently reported to deliver different bioactive molecules such as carbohydrates (heparin), chemotherapeutic agents (doxorubicin), small organic molecules (anti-coagulants), nucleic acids (siRNA), and proteins (growth factors and hormones). Protein therapeutics played a fundamental role in treatment of various chronic and some autoimmune diseases. For instance insulin has been used in treatment of diabetes. However, being a protein in nature, insulin delivery is limited by its instability, short half-life, and easy denaturation when administered orally. To overcome these challenges, and as highlighted in this review article, much research efforts have been recently devoted to design and develop convenient smart controlled nanosystems for protein therapeutics delivery.

  18. The Research Progress of Targeted Drug Delivery Systems

    Science.gov (United States)

    Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

    2017-06-01

    Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

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

    Science.gov (United States)

    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.

  20. Nanodiamond and its application to drug delivery

    Directory of Open Access Journals (Sweden)

    Eiji Osawa

    2012-08-01

    Full Text Available Quasi-spherical diamond crystals having an average diameter of 3.7±0.6 nm are attracting much attention as an ideal material in carbon nanotechnology. In contrast to the other popular nanocarbons including fullerenes, carbon nanotubes and graphenes, our single-nanodiamond can be produced in uniform shape/size on industrial scale. Thus, the most serious problem in nanocarbon industry that persisted in the past 25 years, namely the technical failure to produce highly crystalline nanocarbons in narrow shape/size range does not exist in our diamond from the beginning. Among potential applications of the single-nanodiamond under development, this review concentrates on its highly promising role as a drug carrier, especially for therapeutic-resistant cancer. An interesting possibility of intercalation is proposed as the mechanism of drug transport through blood, which takes into accounts of the spontaneous formation of nanographene layer on the [111] facets, which is then extensively oxidized during oxidative soot removal process to give nanographene oxide partial surface, capable of intercalating drug molecules to prevent them from leaking and causing undesirable side effects during transportation to target malignant cells. A perspective of quantifying the drug delivery process by anticipating orders of magnitude in the number of administered detonation nanodiamond (DND particles is suggested.

  1. Adapalene microemulsion for transfollicular drug delivery.

    Science.gov (United States)

    Bhatia, Gaurav; Zhou, Yingcong; Banga, Ajay K

    2013-08-01

    The aim of this study was to develop a microemulsion formulation of adapalene for transfollicular delivery. A pseudoternary phase diagram was developed for microemulsion consisting of oleic acid as oil phase, tween 20 as surfactant, Transcutol® as cosurfactant, and deionized water. Differential tape stripping and confocal laser scanning microscopy were performed to determine the penetration of microemulsion through hair follicles. Transmission electron microscopy, dynamic light scattering, polarizing light microscopy, and differential scanning calorimetry were performed to characterize the microstructures of microemulsion. The pH and viscosity of the microemulsions were also determined. Permeation studies were carried out in vitro on porcine ear skin over a period of 24 h using Franz diffusion cells. The drug penetration in the hair follicles increased from 0.109 ± 0.03 to 0.292 ± 0.094 μg, as the microstructure of microemulsion shifted from oil-in-water to bi-continuous, with increase in water content of microemulsion. Confocal laser scanning microscopy images suggested that hair follicles provided the path for transfollicular permeation of adapalene microemulsion. These results suggest that microemulsion penetrated through hair follicles and are promising for transfollicular drug delivery. Copyright © 2013 Wiley Periodicals, Inc.

  2. 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)

  3. 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.

  4. Modulation of electrostatic interactions to improve controlled drug delivery from nanogels

    Energy Technology Data Exchange (ETDEWEB)

    Mauri, Emanuele; Chincarini, Giulia M.F.; Rigamonti, Riccardo; Magagnin, Luca; Sacchetti, Alessandro, E-mail: alessandro.sacchetti@polimi.it; Rossi, Filippo, E-mail: filippo.rossi@polimi.it

    2017-03-01

    The synthesis of nanogels as devices capable to maintain the drug level within a desired range for a long and sustained period of time is a leading strategy in controlled drug delivery. However, with respect to the good results obtained with antibodies and peptides there are a lot of problems related to the quick and uncontrolled diffusion of small hydrophilic molecules through polymeric network pores. For these reasons research community is pointing toward the use of click strategies to reduce release rates of the linked drugs to the polymer chains. Here we propose an alternative method that considers the electrostatic interactions between polymeric chains and drugs to tune the release kinetics from nanogel network. The main advantage of these systems lies in the fact that the carried drugs are not modified and no chemical reactions take place during their loading and release. In this work we synthesized PEG-PEI based nanogels with different protonation degrees and the release kinetics with charged and uncharged drug mimetics (sodium fluorescein, SF, and rhodamine B, RhB) were studied. Moreover, also the effect of counterion used to induce protonation was taken into account in order to build a tunable drug delivery system able to provide multiple release rates with the same device. - Highlights: • The design of nanogels as drug delivery systems based on electrostatic interaction among drug and polymers is proposed. • Nanogels can be synthetized tuning their positive charge density, according to the protonation of PEI at different pH. • No biorthogonal chemistry strategies are applied to the polymers or drugs. • Drug release is efficiently modulated by charge density of PEI chains. • The effect of counterion on nanogel synthesis is investigated and allows controlling the drug release.

  5. Structural changes on polymeric nanoparticles induced by hydrophobic drug entrapment

    Czech Academy of Sciences Publication Activity Database

    Jäger, Alessandro; Jäger, Eliezer; Giacomelli, F. C.; Nallet, F.; Steinhart, Miloš; Putaux, J.-L.; Konefal, Rafal; Spěváček, Jiří; Ulbrich, Karel; Štěpánek, Petr

    2018-01-01

    Roč. 538, 5 February (2018), s. 238-249 ISSN 0927-7757 R&D Projects: GA ČR(CZ) GA17-09998S; GA ČR(CZ) GA15-13853S Grant - others:AV ČR(CZ) MSM200501606 Program:Program na podporu mezinárodní spolupráce začínajících výzkumných pracovníků Institutional support: RVO:61389013 Keywords : polymer nanoparticles * drug delivery * paclitaxel Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 2.714, year: 2016

  6. Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design.

    Science.gov (United States)

    Dabhi, Mahesh R; Nagori, Stavan A; Gohel, Mukesh C; Parikh, Rajesh K; Sheth, Navin R

    2010-01-01

    Smart gel periodontal drug delivery systems (SGPDDS) containing gellan gum (0.1-0.8% w/v), lutrol F127 (14, 16, and 18% w/v), and ornidazole (1% w/v) were designed for the treatment of periodontal diseases. Each formulation was characterized in terms of in vitro gelling capacity, viscosity, rheology, content uniformity, in vitro drug release, and syringeability. In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.8% w/v of gellan gum and 16% w/v of lutrol F127 exhibited superior physical characteristics.

  7. Factors affecting the stability of drug-loaded polymeric micelles and strategies for improvement

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Weisai; Li, Caibin; Wang, Zhiyu; Zhang, Wenli, E-mail: zwllz@163.com; Liu, Jianping, E-mail: liujianpingljp@hotmail.com [China Pharmaceutical University, Department of Pharmaceutics (China)

    2016-09-15

    Polymeric micelles (PMs) self-assembled by amphiphilic block copolymers have been used as promising nanocarriers for tumor-targeted delivery due to their favorable properties, such as excellent biocompatibility, prolonged circulation time, favorable particle sizes (10–100 nm) to utilize enhanced permeability and retention effect and the possibility for functionalization. However, PMs can be easily destroyed due to dilution of body fluid and the absorption of proteins in system circulation, which may induce drug leakage from these micelles before reaching the target sites and compromise the therapeutic effect. This paper reviewed the factors that influence stability of micelles in terms of thermodynamics and kinetics consist of the critical micelle concentration of block copolymers, glass transition temperature of hydrophobic segments and polymer–polymer and polymer–cargo interaction. In addition, some effective strategies to improve the stability of micelles were also summarized.Graphical Abstract.

  8. Fractional CO(2) laser-assisted drug delivery

    DEFF Research Database (Denmark)

    Haedersdal, Merete; Sakamoto, Fernanda H; Farinelli, William A

    2010-01-01

    Ablative fractional resurfacing (AFR) creates vertical channels that might assist the delivery of topically applied drugs into skin. The purpose of this study was to evaluate drug delivery by CO(2) laser AFR using methyl 5-aminolevulinate (MAL), a porphyrin precursor, as a test drug....

  9. Polymeric Micelles with Ionic Cores Containing Biodegradable Crosslinks for Delivery of Chemotherapeutic Agents

    OpenAIRE

    Kim, Jong Oh; Sahay, Gaurav; Kabanov, Alexander V.; Bronich, Tatiana K.

    2010-01-01

    Novel functional polymeric nanocarriers with ionic cores containing biodegradable cross-links were developed for delivery of chemotherapeutic agents. Block ionomer complexes (BIC) of poly(ethylene oxide)-b-poly(methacylic acid) (PEO-b-PMA) and divalent metal cations (Ca2+) were utilized as templates. Disulfide bonds were introduced into the ionic cores by using cystamine as a biodegradable cross-linker. The resulting cross-linked micelles with disulfide bonds represented soft, hydrogel-like n...

  10. Polymer matrices obtained by ionizing radiation for using in controlled drug delivery systems

    International Nuclear Information System (INIS)

    Martellini, Flavia

    1998-01-01

    Two kinds of controlled drug delivery system were obtained by gamma radiation induced polymerization. One of the system was obtained from an acrylic derivative of acetaminophen (40-hydroxyacetanilide), by copolymerization of 4-(acryloyloxy) acetanilide and N,N-dimethylacrylamide (DMAA) in dimethylformamide solution with 0,16 kGy/h dose rate and 54 Gy dose. The values of reactivity rate, r-D MAA = 0,31 ± 0,02 e r AOA -0,07 ± 0,12, were determined by Fineman-Ross method. The acetaminophen hydrolysis was carried out in alkaline and enzymatic (trypsin) media. Another kind of drug delivery system studied was solvent controlled type, being the drug immobilized in the hydrogel,. The hydrogels prepared by radiation polymerization of acryloyl-L-propine methylester (A-Pro-OMe) with 10 Gy dose, showed thermosensible property, swelling or shrinking in water with decreased or increased temperatures. The hydrogels were obtained with different crosslink density, trimethylolpropane trimethacrylate, and the monomers N, N-dimethyl acrylamide (DMAA) and 2-cyanoethyl acrylate to study the influence of the composition in the drug delivery rate. It was verified that the porous size besides being a characteristic of the matrix composition, it was also temperature dependent (thermosensible). The analgesic drug acetaminophen was immobilized by entrapment and by physical adsorption into the hydrogels matrices for 'in vitro' study. The insulin was immobilized by adsorption for 'in vivo' study. (author)

  11. Drug delivery with microsecond laser pulses into gelatin

    Science.gov (United States)

    Shangguan, Hanqun; Casperson, Lee W.; Shearin, Alan; Gregory, Kenton W.; Prahl, Scott A.

    1996-07-01

    Photoacoustic drug delivery is a technique for localized drug delivery by laser-induced hydrodynamic pressure following cavitation bubble expansion and collapse. Photoacoustic drug delivery was investigated on gelatin-based thrombus models with planar and cylindrical geometries by use of one microsecond laser pulses. Solutions of a hydrophobic dye in mineral oil permitted monitoring of delivered colored oil into clear gelatin-based thrombus models. Cavitation bubble development and photoacoustic drug delivery were visualized with flash photography. This study demonstrated that cavitation is the governing mechanism for photoacoustic drug delivery, and the deepest penetration of colored oil in gels followed the bubble collapse. Spatial distribution measurements revealed that colored oil could be driven a few millimeters into the gels in both axial and radial directions, and the penetration was less than 500 mu m when the gelatin structure was not fractured. localized drug delivery, cavitation bubble, laser thrombolysis.

  12. Current trends in microsponge drug delivery system.

    Science.gov (United States)

    Gangadharappa, H V; Gupta, N Vishal; Prasad M, Sarat Chandra; Shivakumar, H G

    2013-08-01

    Microsponge is a microscopic sphere capable of absorbing skin secretions, therefore reducing the oiliness of the skin. Microsponge having particle size of 10-25 microns in diameter, have wide range of entrapment of various ingredients in a single microsponges system and release them at desired rates. Conventional topical preparations have various disadvantages due to irritancy, odour, greasiness and patient compliance. In many topical dosage forms fail to reach the systemic circulation in sufficient amounts in few cases. These problems overcome by the usage of formulation as microsponge in the areas of research. Drug release in microsponge is done by the external stimuli like pH, temperature and rubbing. It has several advantageous over the other topical preparations in being non-allergenic, non-toxic, non-irritant and non- mutagenic. These microsponges are used in the sun screens, creams, ointments, over-the-counter skin care preparations, recently nanosponge were reported in literature used in delivery of drug by the use of cyclodextrins to enhance the solubility of poorly water soluble drugs, which are meant for topical application.

  13. Functionalization of protein-based nanocages for drug delivery applications.

    Science.gov (United States)

    Schoonen, Lise; van Hest, Jan C M

    2014-07-07

    Traditional drug delivery strategies involve drugs which are not targeted towards the desired tissue. This can lead to undesired side effects, as normal cells are affected by the drugs as well. Therefore, new systems are now being developed which combine targeting functionalities with encapsulation of drug cargo. Protein nanocages are highly promising drug delivery platforms due to their perfectly defined structures, biocompatibility, biodegradability and low toxicity. A variety of protein nanocages have been modified and functionalized for these types of applications. In this review, we aim to give an overview of different types of modifications of protein-based nanocontainers for drug delivery applications.

  14. Modulation of electrostatic interactions to improve controlled drug delivery from nanogels.

    Science.gov (United States)

    Mauri, Emanuele; Chincarini, Giulia M F; Rigamonti, Riccardo; Magagnin, Luca; Sacchetti, Alessandro; Rossi, Filippo

    2017-03-01

    The synthesis of nanogels as devices capable to maintain the drug level within a desired range for a long and sustained period of time is a leading strategy in controlled drug delivery. However, with respect to the good results obtained with antibodies and peptides there are a lot of problems related to the quick and uncontrolled diffusion of small hydrophilic molecules through polymeric network pores. For these reasons research community is pointing toward the use of click strategies to reduce release rates of the linked drugs to the polymer chains. Here we propose an alternative method that considers the electrostatic interactions between polymeric chains and drugs to tune the release kinetics from nanogel network. The main advantage of these systems lies in the fact that the carried drugs are not modified and no chemical reactions take place during their loading and release. In this work we synthesized PEG-PEI based nanogels with different protonation degrees and the release kinetics with charged and uncharged drug mimetics (sodium fluorescein, SF, and rhodamine B, RhB) were studied. Moreover, also the effect of counterion used to induce protonation was taken into account in order to build a tunable drug delivery system able to provide multiple release rates with the same device. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Microneedle arrays for biosensing and drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Joseph; Windmiller, Joshua Ray; Narayan, Roger; Miller, Philip

    2017-08-29

    Methods, structures, and systems are disclosed for biosensing and drug delivery techniques. In one aspect, a device for detecting an analyte and/or releasing a biochemical into a biological fluid can include an array of hollowed needles, in which each needle includes a protruded needle structure including an exterior wall forming a hollow interior and an opening at a terminal end of the protruded needle structure that exposes the hollow interior, and a probe inside the exterior wall to interact with one or more chemical or biological substances that come in contact with the probe via the opening to produce a probe sensing signal, and an array of wires that are coupled to probes of the array of hollowed needles, respectively, each wire being electrically conductive to transmit the probe sensing signal produced by a respective probe.

  16. Microneedle arrays for biosensing and drug delivery

    Science.gov (United States)

    Wang, Joseph; Windmiller, Joshua Ray; Narayan, Roger; Miller, Philip; Polsky, Ronen; Edwards, Thayne L.

    2017-08-22

    Methods, structures, and systems are disclosed for biosensing and drug delivery techniques. In one aspect, a^ device for detecting an analyte and/or releasing a biochemical into a biological fluid can include an array of hollowed needles, in which each needle includes a protruded needle structure including an exterior wall forming a hollow interior and an opening at a terminal end of the protruded needle structure that exposes the hollow interior, and a probe inside the exterior wall to interact with one or more chemical or biological substances that come in contact with the probe via the opening to produce a probe sensing signal, and an array of wires that are coupled to probes of the array of hollowed needles, respectively, each wire being electrically conductive to transmit the probe sensing signal produced by a respective probe.

  17. Microencapsulation: A promising technique for controlled drug delivery.

    Science.gov (United States)

    Singh, M N; Hemant, K S Y; Ram, M; Shivakumar, H G

    2010-07-01

    MICROPARTICLES OFFER VARIOUS SIGNIFICANT ADVANTAGES AS DRUG DELIVERY SYSTEMS, INCLUDING: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed.

  18. Porous Polymer Drug-Eluting Coating Prepared by Radiation Induced Polymerization

    International Nuclear Information System (INIS)

    Veres, M.; Beiler, B.; Himics, L.; Tóth, S.; Koós, M.

    2010-01-01

    Many areas of modern medicine are almost unimaginable without the use of different kinds of implants. They used as replacements, supports, auxiliary devices etc. for various parts or functions of the body. Their use has many advantages, however there could be some drawbacks too, like the possibility of rejection, inflammation and other side-effects. Many of these drawbacks are directly related to the materials used for the implant fabrication. Coatings are widely used to eliminate the unwanted effects appearing after the implantation. In addition to the protection and separation of tissues from the implant material they could also enhance the functionality and the acceptance of the artificial device and also promote the regeneration of the tissues after the intervention. Drug-eluting coatings are a good example for the latter. By delivery and controlled elution of drugs they could actively suppress inflammatory reactions, allergy and rejection of the implant, and their activity is localized to the place where these effects could mainly occur – to the region of the implant. This project is aimed to develop a drug-eluting porous polymer coating by radiation induced polymerization that can be used in different medical implants. The primary objects for this research are coronary stents however these porous layers could have perspective in other types of medical devices too. The main objectives are to develop a method for coating the surface of medical grade metallic alloy wires, plates and tubes with a porous polymer nanocomposite layer prepared by radiation induced polymerization and to characterize the obtained coatings

  19. Porous Polymer Drug-Eluting Coating Prepared by Radiation Induced Polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Veres, M.; Beiler, B.; Himics, L.; Tóth, S.; Koós, M., E-mail: vm@szfki.hu [Hungarian Academy of Sciences, Research Institute for Solid State Physics and Optics, Department of Laser Applications, Konkoly Thege Miklós ut 29-33, 1121 Budapest, P.O. Box 49, 1525 Budapest (Hungary)

    2010-07-01

    Many areas of modern medicine are almost unimaginable without the use of different kinds of implants. They used as replacements, supports, auxiliary devices etc. for various parts or functions of the body. Their use has many advantages, however there could be some drawbacks too, like the possibility of rejection, inflammation and other side-effects. Many of these drawbacks are directly related to the materials used for the implant fabrication. Coatings are widely used to eliminate the unwanted effects appearing after the implantation. In addition to the protection and separation of tissues from the implant material they could also enhance the functionality and the acceptance of the artificial device and also promote the regeneration of the tissues after the intervention. Drug-eluting coatings are a good example for the latter. By delivery and controlled elution of drugs they could actively suppress inflammatory reactions, allergy and rejection of the implant, and their activity is localized to the place where these effects could mainly occur – to the region of the implant. This project is aimed to develop a drug-eluting porous polymer coating by radiation induced polymerization that can be used in different medical implants. The primary objects for this research are coronary stents however these porous layers could have perspective in other types of medical devices too. The main objectives are to develop a method for coating the surface of medical grade metallic alloy wires, plates and tubes with a porous polymer nanocomposite layer prepared by radiation induced polymerization and to characterize the obtained coatings.

  20. Topical and transdermal drug delivery: principles and practice

    National Research Council Canada - National Science Library

    Benson, Heather A. E; Watkinson, Adam C

    2012-01-01

    .... Providing an overview of the current science in drug and cosmetic application to and through the skin, Topical and Transdermal Drug Delivery includes treatment of skin conditions, skin permeation...

  1. A Microfluidic Ion Pump for In Vivo Drug Delivery

    KAUST Repository

    Uguz, Ilke; Proctor, Christopher M.; Curto, Vincenzo F.; Pappa, Anna-Maria; Donahue, Mary J.; Ferro, Magali; Owens, Ró isí n M.; Khodagholy, Dion; Inal, Sahika; Malliaras, George G.

    2017-01-01

    Implantable devices offer an alternative to systemic delivery of drugs for the treatment of neurological disorders. A microfluidic ion pump (µFIP), capable of delivering a drug without the solvent through electrophoresis, is developed. The device

  2. Nanostructured porous silicon-mediated drug delivery.

    Science.gov (United States)

    Martín-Palma, Raúl J; Hernández-Montelongo, Jacobo; Torres-Costa, Vicente; Manso-Silván, Miguel; Muñoz-Noval, Álvaro

    2014-08-01

    The particular properties of nanostructured porous silicon (nanoPS) make it an attractive material for controlled and localized release of therapeutics within the body, aiming at increased efficacy and reduced risks of potential side effects. Since this is a rapidly evolving field as a consequence of the number of research groups involved, a critical review of the state of the art is necessary. In this work, the most promising and successful applications of nanoPS in the field of drug delivery are reviewed and discussed. Two key issues such as drug loading and release are also analyzed in detail. The development of multifunctional (hybrid) systems, aiming at imparting additional functionalities to the nanoPS particles such as luminescence, magnetic response and/or plasmonic effects (allowing simultaneous tracking and guiding), is also examined. Nanostructured materials based on silicon are promising platforms for pharmaceutical applications given their ability to degrade and low toxicity. However, a very limited number of clinical applications have been demonstrated so far.

  3. Sensor-integrated polymer actuators for closed-loop drug delivery system

    Science.gov (United States)

    Xu, Han; Wang, Chunlei; Kulinsky, Lawrence; Zoval, Jim; Madou, Marc

    2006-03-01

    This work presents manufacturing and testing of a closed-loop drug delivery system where drug release is achieved by an electrochemical actuation of an array of polymeric valves on a set of drug reservoirs. The valves are based on bi-layer structures made of polypyrrole/gold in the shape of a flap that is hinged on one side of a valve seat. Drugs stored in the underlying chambers are released by bending the bi-layer flaps back with a small applied bias. These polymeric valves simultaneously function as both drug release components and biological/chemical sensors responding to a specific biological or environmental stimulus. The sensors may send signals to the control module to realize closed-loop control of the drug release. In this study a glucose sensor has been integrated with the polymeric actuators through immobilization of glucose oxidase(GOx) within polypyrrole(PPy) valves. Sensitivities per unit area of the integrated glucose sensor have been measured and compared before and after the actuation of the sensor/actuator PPy/DBS/GOx film. Other sensing parameters such as linear range and response time were discussed as well. Using an array of these sensor/actuator cells, the amount of released drug, e.g. insulin, can be precisely controlled according to the surrounding glucose concentration detected by the glucose sensor. Activation of these reservoirs can be triggered either by the signal from the sensor, or by the signal from the operator. This approach also serves as the initial step to use the proposed system as an implantable drug delivery platform in the future.

  4. Magnetically responsive microparticles for targeted drug and radionuclide delivery

    International Nuclear Information System (INIS)

    Kaminski, M. D.; Ghebremeskel, A. N.; Nunez, L.; Kasza, K. E.; Chang, F.; Chien, T.-H.; Fisher, P. F.; Eastman, J. A.; Rosengart, A. J.; McDonald, L.; Xie, Y.; Johns, L.; Pytel, P.; Hafeli, U. O.

    2004-01-01

    We are currently investigating the use of magnetic particles--polymeric-based spheres containing dispersed magnetic nanocrystalline phases--for the precise delivery of drugs via the human vasculature. According to this review, meticulously prepared magnetic drug targeting holds promise as a safe and effective method of delivering drugs to specific organ, tissue or cellular targets. We have critically examined the wide range of approaches in the design and implementation of magnetic-particle-based drug delivery systems to date, including magnetic particle preparation, drug encapsulation, biostability, biocompatibility, toxicity, magnetic field designs, and clinical trials. However, we strongly believe that there are several limitations with past developments that need to be addressed to enable significant strides in the field. First, particle size has to be carefully chosen. Micrometer-sized magnetic particles are better attracted over a distance than nanometer sized magnetic particles by a constant magnetic field gradient, and particle sizes up to 1 (micro)m show a much better accumulation with no apparent side effects in small animal models, since the smallest blood vessels have an inner diameter of 5-7 (micro)m. Nanometer-sized particles <70 nm will accumulate in organ fenestrations despite an effective surface stabilizer. To be suitable for future human applications, our experimental approach synthesizes the magnetic drug carrier according to specific predefined outcome metrics: monodisperse population in a size range of 100 nm to 1.0 (micro)m, non-toxic, with appropriate magnetic properties, and demonstrating successful in vitro and in vivo tests. Another important variable offering possible improvement is surface polarity, which is expected to prolong particle half-life in circulation and modify biodistribution and stability of drugs in the body. The molecules in the blood that are responsible for enhancing the uptake of particles by the reticuloendothelial

  5. 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.

  6. Porous silicon-cyclodextrin based polymer composites for drug delivery applications.

    Science.gov (United States)

    Hernandez-Montelongo, J; Naveas, N; Degoutin, S; Tabary, N; Chai, F; Spampinato, V; Ceccone, G; Rossi, F; Torres-Costa, V; Manso-Silvan, M; Martel, B

    2014-09-22

    One of the main applications of porous silicon (PSi) in biomedicine is drug release, either as a single material or as a part of a composite. PSi composites are attractive candidates for drug delivery systems because they can display new chemical and physical characteristics, which are not exhibited by the individual constituents alone. Since cyclodextrin-based polymers have been proven efficient materials for drug delivery, in this work β-cyclodextrin-citric acid in-situ polymerization was used to functionalize two kinds of PSi (nanoporous and macroporous). The synthesized composites were characterized by microscopy techniques (SEM and AFM), physicochemical methods (ATR-FTIR, XPS, water contact angle, TGA and TBO titration) and a preliminary biological assay was performed. Both systems were tested as drug delivery platforms with two different model drugs, namely, ciprofloxacin (an antibiotic) and prednisolone (an anti-inflammatory), in two different media: pure water and PBS solution. Results show that both kinds of PSi/β-cyclodextrin-citric acid polymer composites, nano- and macro-, provide enhanced release control for drug delivery applications than non-functionalized PSi samples. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Production of drug-loaded polymeric nanoparticles by electrospraying technology.

    Science.gov (United States)

    Sosnik, Alejandro

    2014-09-01

    The pharmaceutical industry struggles with high attrition. The outbreak of pharmaceutical micro/nanotechnology has been fundamental to overcome several (bio)pharmaceutic drawbacks of drugs such as poor aqueous solubility, physicochemical instability, short half life, inappropriate biodistribution and toxicity. The spatiotemporal release of drugs directly in the site of action and the restriction of the systemic exposure by means of nanotechnology has notoriously improved drug safety ratios. At the same time, the development of production methods that are cost-effective, scalable and reproducible under industrial settings becomes crucial to ensure the clinical translation of any development. The electrospraying process, also known as electrohydrodynamic atomization (EHDA), is a single-stage technique of liquid atomization by means of electrical forces that enables the generation of micro/nanoparticles with especially narrow size distribution. EHDA is based on the ability of an electric field to deform the interface of a liquid drop and break it into smaller mono-disperse droplets. The main advantageous features over conventional methods are the possibility to produce particles without the use of surfactants, at ambient temperature and pressure and with maximum encapsulation efficiency due to the absence of an external medium that allows the migration and/or dissolution of water-soluble cargos. In addition, the mild conditions are optimal for the encapsulation of thermo-sensitive cargos. The present article overviews the applications of this technology for the production of nano-drug delivery systems and discusses its key role to support the transfer of a broad spectrum of nanomedicines to the market.

  8. pH- and ion-sensitive polymers for drug delivery.

    Science.gov (United States)

    Yoshida, Takayuki; Lai, Tsz Chung; Kwon, Glen S; Sako, Kazuhiro

    2013-11-01

    Drug delivery systems (DDSs) are important for effective, safe, and convenient administration of drugs. pH- and ion-responsive polymers have been widely employed in DDS for site-specific drug release due to their abilities to exploit specific pH- or ion-gradients in the human body. Having pH-sensitivity, cationic polymers can mask the taste of drugs and release drugs in the stomach by responding to gastric low pH. Anionic polymers responsive to intestinal high pH are used for preventing gastric degradation of drug, colon drug delivery and achieving high bioavailability of weak basic drugs. Tumor-targeted DDSs have been developed based on polymers with imidazole groups or poly(β-amino ester) responsive to tumoral low pH. Polymers with pH-sensitive chemical linkages, such as hydrazone, acetal, ortho ester and vinyl ester, pH-sensitive cell-penetrating peptides and cationic polymers undergoing pH-dependent protonation have been studied to utilize the pH gradient along the endocytic pathway for intracellular drug delivery. As ion-sensitive polymers, ion-exchange resins are frequently used for taste-masking, counterion-responsive drug release and sustained drug release. Polymers responding to ions in the saliva and gastrointestinal fluids are also used for controlled drug release in oral drug formulations. Stimuli-responsive DDSs are important for achieving site-specific and controlled drug release; however, intraindividual, interindividual and intercellular variations of pH should be considered when designing DDSs or drug products. Combination of polymers and other components, and deeper understanding of human physiology are important for development of pH- and ion-sensitive polymeric DDS products for patients.

  9. pH- and ion-sensitive polymers for drug delivery

    Science.gov (United States)

    Yoshida, Takayuki; Lai, Tsz Chung; Kwon, Glen S; Sako, Kazuhiro

    2013-01-01

    Introduction Drug delivery systems (DDSs) are important for effective, safe, and convenient administration of drugs. pH- and ion-responsive polymers have been widely employed in DDS for site-specific drug release due to their abilities to exploit specific pH- or ion-gradients in the human body. Areas covered Having pH-sensitivity, cationic polymers can mask the taste of drugs and release drugs in the stomach by responding to gastric low pH. Anionic polymers responsive to intestinal high pH are used for preventing gastric degradation of drug, colon drug delivery and achieving high bioavailability of weak basic drugs. Tumor-targeted DDSs have been developed based on polymers with imidazole groups or poly(β-amino ester) responsive to tumoral low pH. Polymers with pH-sensitive chemical linkages, such as hydrazone, acetal, ortho ester and vinyl ester, pH-sensitive cell-penetrating peptides and cationic polymers undergoing pH-dependent protonation have been studied to utilize the pH gradient along the endocytic pathway for intracellular drug delivery. As ion-sensitive polymers, ion-exchange resins are frequently used for taste-masking, counterion-responsive drug release and sustained drug release. Polymers responding to ions in the saliva and gastrointestinal fluids are also used for controlled drug release in oral drug formulations. Expert opinion Stimuli-responsive DDSs are important for achieving site-specific and controlled drug release; however, intraindividual, interindividual and intercellular variations of pH should be considered when designing DDSs or drug products. Combination of polymers and other components, and deeper understanding of human physiology are important for development of pH- and ion-sensitive polymeric DDS products for patients. PMID:23930949

  10. Nanocarriers in ocular drug delivery: an update review.

    Science.gov (United States)

    Wadhwa, Sheetu; Paliwal, Rishi; Paliwal, Shivani Rai; Vyas, S P

    2009-01-01

    Controlled drug delivery to eye is one of the most challenging fields of pharmaceutical research. Low drug-contact time and poor ocular bioavailability due to drainage of solution, tear turnover and its dilution or lacrimation are the problems associated with conventional systems. In addition, anatomical barriers and physiological conditions of eye are also important parameters which control designing of drug delivery systems. Nanosized carriers like micro/nano-suspensions, liposome, niosome, dendrimer, nanoparticles, ocular inserts, implants, hydrogels and prodrug approaches have been developed for this purpose. These novel systems offer manifold advantages over conventional systems as they increase the efficiency of drug delivery by improving the release profile and also reduce drug toxicity. Conventional delivery systems get diluted with tear, washed away through the lacrimal gland and usually require administering at regular time intervals whereas nanocarriers release drug at constant rate for a prolonged period of time and thus enhance its absorption and site specific delivery. This review presents an overview of the various aspects of the ocular drug delivery, with special emphasis on nanocarrier based strategies, including structure of eye, its barriers, delivery routes and the challenges/limitations associated with development of novel nanocarriers. The recent progresses in therapy of ocular disease like gene therapy have also been included so that future options should also be considered from the delivery point of view. Recent progress in the delivery of proteins and peptides via ocular route has also been incorporated for reader benefit.

  11. Scleroglucan: A Versatile Polysaccharide for Modified Drug Delivery

    Directory of Open Access Journals (Sweden)

    Franco Alhaique

    2005-01-01

    Full Text Available Scleroglucan is a natural polysaccharide, produced by fungi of the genus Sclerotium, that has been extensively studied for various commercial applications (secondary oil recovery, ceramic glazes, food, paints, etc. and also shows several interesting pharmacological properties. This review focuses its attention on the use of scleroglucan, and some derivatives, in the field of pharmaceutics and in particular for the formulation of modified-release dosage forms. The reported investigations refer mainly to the following topics: natural scleroglucan suitable for the preparation of sustained release tablets and ocular formulations; oxidized and crosslinked scleroglucan used as a matrix for dosage forms sensitive to environmental conditions; co-crosslinked scleroglucan/gellan whose delivery rate can be affected by calcium ions. Furthermore, a novel hydrogel obtained with this polysaccharide and borate ions is described, and the particular structure of this hydrogel network has been interpreted in terms of conformational analysis and molecular dynamics. Profound attention is devoted to the mechanisms involved in drug release from the tested dosage forms that depend, according to the specific preparation, on swelling and/or diffusion. Experimental data are also discussed on the basis of a mathematical approach that allows a better understanding of the behavior of the tested polymeric materials.

  12. Drug Delivery Systems: A New Frontier in Nano-technology

    Directory of Open Access Journals (Sweden)

    Chamindri Witharana

    2017-09-01

    Full Text Available Nano-technology is a recent advancement in science, defined as “Science, engineering, and technology conducted at the Nano scale” (National nanotechnology initiatives in USA. Applications of Nano-technology cover a vast range from basic material science, personal care applications, agriculture, and medicine. Nano-technology is used in field of medicine for treatment, diagnostic, monitoring, genetic engineering, and drug delivery. There are two main types of Nano Particles (NPs used in drug delivery; organic NPs and inorganic NPs. In drug delivery, the drug-Nano- Particle (NP conjugate should be able to deliver drugs to the target site without degradation in gastrointestinal track and without reducing drug activity. Further, it should attack to target cells without causing any adverse effects. The ultimate goal of NP drug delivery is to improve proper treatment, effectiveness, less side effects with safety and patient adherence as well as reduction in the cost.

  13. Galactosyl Pentadecene Reversibly Enhances Transdermal and Topical Drug Delivery

    Czech Academy of Sciences Publication Activity Database

    Kopečná, M.; Macháček, M.; Prchalová, Eva; Štěpánek, P.; Drašar, P.; Kotora, Martin; Vávrová, K.

    2017-01-01

    Roč. 34, č. 10 (2017), s. 2097-2108 ISSN 0724-8741 Institutional support: RVO:61388963 Keywords : galactoside * penetration enhancers * sugar * topical drug delivery * transdermal drug delivery Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Pharmacology and pharmacy Impact factor: 3.002, year: 2016

  14. Targeted drug delivery to magnetic implants for therapeutic applications

    International Nuclear Information System (INIS)

    Yellen, Benjamin B.; Forbes, Zachary G.; Halverson, Derek S.; Fridman, Gregory; Barbee, Kenneth A.; Chorny, Michael; Levy, Robert; Friedman, Gary

    2005-01-01

    A new method for locally targeted drug delivery is proposed that employs magnetic implants placed directly in the cardiovascular system to attract injected magnetic carriers. Theoretical simulations and experimental results support the assumption that using magnetic implants in combination with externally applied magnetic field will optimize the delivery of magnetic drug to selected sites within a subject

  15. Role of Nanodiamonds in Drug Delivery and Stem Cell Therapy.

    Science.gov (United States)

    Ansari, Shakeel Ahmed; Satar, Rukhsana; Jafri, Mohammad Alam; Rasool, Mahmood; Ahmad, Waseem; Kashif Zaidi, Syed

    2016-09-01

    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. Nanodiamonds (NDs) have contributed significantly in the development of highly efficient and successful drug delivery systems, and in stem cell therapy. Drug delivery through NDs is an intricate and complex process that deserves special attention to unravel underlying molecular mechanisms in order to overcome certain bottlenecks associated with it. It has already been established that NDs based drug delivery systems have excellent biocompatibility, nontoxicity, photostability and facile surface functionalization properties. There is mounting evidence that suggests that such conjugated delivery systems well retain the properties of nanoparticles like small size, large surface area to volume ratio that provide greater biocatalytic activity to the attached drug in terms of selectivity, loading and stability. NDs based drug delivery systems may form the basis for the development of effective novel drug delivery vehicles with salient features that may facilitate their utility in fluorescence imaging, target specificity and sustainedrelease.

  16. Drug Delivery Approaches for the Treatment of Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Farideh Ordikhani

    2016-07-01

    Full Text Available Cervical cancer is a highly prevalent cancer that affects women around the world. With the availability of new technologies, researchers have increased their efforts to develop new drug delivery systems in cervical cancer chemotherapy. In this review, we summarized some of the recent research in systematic and localized drug delivery systems and compared the advantages and disadvantages of these methods.

  17. Sustained delivery of plasmid DNA from polymeric scaffolds for tissue engineering.

    Science.gov (United States)

    Storrie, Hannah; Mooney, David J

    2006-07-07

    The encapsulation of DNA into polymeric depot systems can be used to spatially and temporally control DNA release, leading to a sustained, local delivery of therapeutic factors for tissue regeneration. Prior to encapsulation, DNA may be condensed with cationic polymers to decrease particle size, protect DNA from degradation, promote interaction with cell membranes, and facilitate endosomal release via the proton sponge effect. DNA has been encapsulated with either natural or synthetic polymers to form micro- and nanospheres, porous scaffolds and hydrogels for sustained DNA release and the polymer physical and chemical properties have been shown to influence transfection efficiency. Polymeric depot systems have been applied for bone, skin, and nerve regeneration as well as therapeutic angiogenesis, indicating the broad applicability of these systems for tissue engineering.

  18. 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.

  19. 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.

  20. Otic drug delivery systems: formulation principles and recent developments.

    Science.gov (United States)

    Liu, Xu; Li, Mingshuang; Smyth, Hugh; Zhang, Feng

    2018-04-25

    Disorders of the ear severely impact the quality of life of millions of people, but the treatment of these disorders is an ongoing, but often overlooked challenge particularly in terms of formulation design and product development. The prevalence of ear disorders has spurred significant efforts to develop new therapeutic agents, but perhaps less innovation has been applied to new drug delivery systems to improve the efficacy of ear disease treatments. This review provides a brief overview of physiology, major diseases, and current therapies used via the otic route of administration. The primary focuses are on the various administration routes and their formulation principles. The article also presents recent advances in otic drug deliveries as well as potential limitations. Otic drug delivery technology will likely evolve in the next decade and more efficient or specific treatments for ear disease will arise from the development of less invasive drug delivery methods, safe and highly controlled drug delivery systems, and biotechnology targeting therapies.

  1. 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

  2. Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities

    Directory of Open Access Journals (Sweden)

    Maarten Janssen

    2014-03-01

    Full Text Available Osteoarthritis (OA is a big burden of disease worldwide and one of the most common causes of disability in the adult population. Currently applied therapies consist of physical therapy, oral medication, intra-articular injections, and surgical interventions, with the main goal being to reduce pain and improve function and quality of life. Intra-articular (IA administration of drugs has potential benefits in OA treatment because it minimizes systemic bioavailability and side effects associated with oral administration of drugs without compromising the therapeutic effect in the joint. However, IA drug residence time is short and there is a clinical need for a vehicle that is able to provide a sustained release long enough for IA therapy to fulfill its promise. This review summarizes the use of different polymeric systems and the incorporated drugs for IA drug delivery in the osteoarthritic joint with a primary focus on clinical needs and opportunities.

  3. Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Sabine Szunerits

    2018-02-01

    Full Text Available Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs, which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field

  4. Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery.

    Science.gov (United States)

    Szunerits, Sabine; Boukherroub, Rabah

    2018-01-01

    Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum , the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section "Frontiers in Bioengineering and Biotechnology," the advances in this field and the handful of

  5. Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery

    Science.gov (United States)

    Szunerits, Sabine; Boukherroub, Rabah

    2018-01-01

    Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field and the handful of

  6. Marine Origin Polysaccharides in Drug Delivery Systems.

    Science.gov (United States)

    Cardoso, Matias J; Costa, Rui R; Mano, João F

    2016-02-05

    Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine.

  7. Marine Origin Polysaccharides in Drug Delivery Systems

    Science.gov (United States)

    Cardoso, Matias J.; Costa, Rui R.; Mano, João F.

    2016-01-01

    Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine. PMID:26861358

  8. Marine Origin Polysaccharides in Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Matias J. Cardoso

    2016-02-01

    Full Text Available Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine.

  9. 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.

  10. Elastic liposomes as novel carriers: recent advances in drug delivery

    Science.gov (United States)

    Hussain, Afzal; Singh, Sima; Sharma, Dinesh; Webster, Thomas J; Shafaat, Kausar; Faruk, Abdul

    2017-01-01

    Elastic liposomes (EL) are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields. PMID:28761343

  11. Noninvasive ocular drug delivery: potential transcorneal and other alternative delivery routes for therapeutic molecules in glaucoma.

    Science.gov (United States)

    Foldvari, Marianna

    2014-01-01

    Drug delivery to the eye is made difficult by multiple barriers (such as the tear film, cornea, and vitreous) between the surface of the eye and the treatment site. These barriers are difficult to surmount for the purposes of drug delivery without causing toxicity. Using nanotechnology tools to control, manipulate, and study delivery systems, new approaches to delivering drugs, genes, and antigens that are effective and safe can be developed. Topical administration to the ocular surface would be the safest method for delivery, as it is noninvasive and painless compared with other delivery methods. However, there is only limited success using topical delivery methods, especially for gene therapy. Current thinking on treatments of the future enabled by nanodelivery systems and the identification of target specificity parameters that require deeper understanding to develop successful topical delivery systems for glaucoma is highlighted.

  12. Recent advances in medicinal chemistry and pharmaceutical technology--strategies for drug delivery to the brain.

    Science.gov (United States)

    Denora, Nunzio; Trapani, Adriana; Laquintana, Valentino; Lopedota, Angela; Trapani, Giuseppe

    2009-01-01

    This paper provides a mini-review of some recent approaches for the treatment of brain pathologies examining both medicinal chemistry and pharmaceutical technology contributions. Medicinal chemistry-based strategies are essentially aimed at the chemical modification of low molecular weight drugs in order to increase their lipophilicity or the design of appropriate prodrugs, although this review will focus primarily on the use of prodrugs and not analog development. Recently, interest has been focused on the design and evaluation of prodrugs that are capable of exploiting one or more of the various endogenous transport systems at the level of the blood brain barrier (BBB). The technological strategies are essentially non-invasive methods of drug delivery to malignancies of the central nervous system (CNS) and are based on the use of nanosystems (colloidal carriers) such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, polymeric micelles and dendrimers. The biodistribution of these nanocarriers can be manipulated by modifying their surface physico-chemical properties or by coating them with surfactants and polyethylene-glycols (PEGs). Liposomes, surfactant coated polymeric nanoparticles, and solid lipid nanoparticles are promising systems for delivery of drugs to tumors of the CNS. This mini-review discusses issues concerning the scope and limitations of both the medicinal chemistry and technological approaches. Based on the current findings, it can be concluded that crossing of the BBB and drug delivery to CNS is extremely complex and requires a multidisciplinary approach such as a close collaboration and common efforts among researchers of several scientific areas, particularly medicinal chemists, biologists and pharmaceutical technologists.

  13. Advances and Challenges of Liposome Assisted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Lisa eSercombe

    2015-12-01

    Full Text Available The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables effective delivery of encapsulated compounds to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of positive results in preclinical studies, the clinical translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biological challenges that still remain, and current clinical and experimental use of liposomes for biomedical applications. The translational obstacles of liposomal technology will also be presented.

  14. Intraperiodontal pocket: An ideal route for local antimicrobial drug delivery

    Directory of Open Access Journals (Sweden)

    Sreeja C Nair

    2012-01-01

    Full Text Available Periodontal pockets act as a natural reservoir filled with gingival crevicular fluid for the controlled release delivery of antimicrobials directly. This article reflects the present status of nonsurgical controlled local intrapocket delivery of antimicrobials in the treatment of periodontitis. These sites have specialty in terms of anatomy, permeability, and their ability to retain a delivery system for a desired length of time. A number of antimicrobial products and the composition of the delivery systems, its use, clinical results, and their release are summarized. The goal in using an intrapocket device for the delivery of an antimicrobial agent is the achievement and maintenance of therapeutic drug concentration for the desired period of time. Novel controlled drug delivery system are capable of improving patient compliance as well as therapeutic efficacy with precise control of the rate by which a particular drug dosage is released from a delivery system without the need for frequent administration. These are considered superior drug delivery system because of low cost, greater stability, non-toxicity, biocompatibility, non-immunogenicity, and are biodegradable in nature. This review also focus on the importance and ideal features of periodontal pockets as a drug delivery platform for designing a suitable dosage form along with its potential advantage and limitations. The microbes in the periodontal pocket could destroy periodontal tissues, and a complete knowledge of these as well as an ideal treatment strategy could be helpful in treating this disease.

  15. Recent trends in challenges and opportunities of Transdermal drug delivery system

    OpenAIRE

    P.M.Patil; P.D.Chaudhari; Jalpa K.Patel; K.A.Kedar; P.P.Katolkar

    2012-01-01

    Drug delivery system relates to the production of a drug, its delivery medium, and the way of administration. Drug delivery systems are even used for administering nitroglycerin. Transdermal drug delivery system is the system in which the delivery of the active ingredients of the drug occurs by the means of skin. Various types of transdermal patches are used. There are various methods to enhance the transdermal drug delivery system. But using microfabricated microneedles drugs are delivered v...

  16. Design, Characterization, and Optimization of Controlled Drug Delivery System Containing Antibiotic Drug/s

    Directory of Open Access Journals (Sweden)

    Apurv Patel

    2016-01-01

    Full Text Available The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients.

  17. Ultrasound-triggered local release of lipophilic drugs from a novel polymeric ultrasound contrast agent

    NARCIS (Netherlands)

    Kooiman, K.; Böhmer, M.R.; Emmer, M.; Vos, Hendrik J.; Chlon, C.; Foppen-Harteveld, M.; Versluis, Michel; de Jong, N.; van Wamel, A.; Hennink, W.E.; Feijen, J.; Sam, A.P.

    2008-01-01

    The advantage of ultrasound contrast agents (UCAs) as drug delivery systems is the ability to non-invasively control the local and triggered release of a drug or gene. In this study we designed and characterized a novel UCA-based drug delivery system, based on polymer-shelled microcapsules filled

  18. Novel engineered systems for oral, mucosal and transdermal drug delivery.

    Science.gov (United States)

    Li, Hairui; Yu, Yuan; Faraji Dana, Sara; Li, Bo; Lee, Chi-Ying; Kang, Lifeng

    2013-08-01

    Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.

  19. A commentary on transdermal drug delivery systems in clinical trials.

    Science.gov (United States)

    Watkinson, Adam C

    2013-09-01

    The number of drugs available as marketed transdermal products is limited to those that exhibit the correct physicochemical and pharmacokinetic properties that enable their effective delivery across the skin. In this respect, there are less than 20 drugs that are currently marketed in the US and EU as products that deliver systemic levels of their active ingredients. An analysis of clinical trials conducted in the transdermal sector shows a similar picture with only nine drugs accounting for approximately 80% of all transdermal clinical trials listed on ClinicalTrials.gov. Those drugs for which there are very few transdermal trials listed consist mostly of molecules that are inherently unsuitable for transdermal delivery and serve as a clear warning to drug developers that the science that governs transdermal drug delivery is well reflected by the successes and failures of drugs in development as well as those that make it to the market. Copyright © 2013 Wiley Periodicals, Inc.

  20. 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.

  1. Design and in vitro evaluation of multiparticulate floating drug delivery system of zolpidem tartarate.

    Science.gov (United States)

    Amrutkar, P P; Chaudhari, P D; Patil, S B

    2012-01-01

    Zolpidem tartarate is a non-benzodiazepine, sedative-hypnotic, which finds its major use in various types of insomnia. The present work relates to development of multiparticulate floating drug delivery system based on gas generation technique to prolong the gastric residence time and to increase the overall bioavailability. Modified release dosage form of zolpidem tartarate adapted to release over a predetermined time period, according to biphasic profile of dissolution, where the first phase is immediate release phase for inducing the sleep and the second phase is modified release phase for maintaining the sleep up to 10 h. The system consists of zolpidem tartarate layered pellets coated with effervescent layer and polymeric membrane. The floating ability and in vitro drug release of the system were dependent on amount of the effervescent agent (sodium bicarbonate) layered onto the drug layered pellets, and coating level of the polymeric membrane (Eudragit(®) NE 30D). The system could float completely within 5 min and maintain the floating over a period of 10 h. The multiparticulate floating delivery system of zolpidem tartarate with rapid floating and modified drug release was obtained. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Extraction and encapsulation of prodigiosin in chitosan microspheres for targeted drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Dozie-Nwachukwu, S.O. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Biotechnology and Genetic Engineering Advanced Laboratory, Sheda Science and Technology Complex (SHESTCO), P.M.B 186, Garki, Abuja, Federal Capital Territory (Nigeria); Danyuo, Y. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Materials Science and Engineering, Kwara State University, Malete (Nigeria); Obayemi, J.D. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States); Odusanya, O.S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Biotechnology and Genetic Engineering Advanced Laboratory, Sheda Science and Technology Complex (SHESTCO), P.M.B 186, Garki, Abuja, Federal Capital Territory (Nigeria); Malatesta, K. [Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States); Soboyejo, W.O., E-mail: soboyejo@princeton.edu [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States); Princeton Institute of Science and Technology of Materials (PRISM), Bowen Hall, 70 Prospect Street, Princeton, NJ 08544 (United States)

    2017-02-01

    The encapsulation of drugs in polymeric materials has brought opportunities to the targeted delivery of chemotherapeutic agents. These polymeric delivery systems are capable of maximizing the therapeutic activity, as well as reducing the side effects of anti-cancer agents. Prodigiosin, a secondary metabolite extracted from the bacteria, Serratia marcescens, exhibits anti-cancer properties. Prodigiosin-loaded chitosan microspheres were prepared via water-in-oil (w/o) emulsion technique, using glutaraldehyde as a cross-linker. The morphologies of the microspheres were studied using scanning electron microscopy. The average sizes of the microspheres were between 40 μm and 60 μm, while the percentage yields ranged from 42 ± 2% to 55.5 ± 3%. The resulting encapsulation efficiencies were between 66.7 ± 3% and 90 ± 4%. The in-vitro drug release from the microspheres was characterized by zeroth order, first order and Higuchi and Korsmeyer-Peppas models. - Highlights: • Prodigiosin of ~ 92.8% purity was extracted from locally isolated Serratia marcescens. • This approach reduces the cost and ensure availability of drugs for cancer treatment. • High encapsulation efficiency which increased with increasing drug:polymer ratio • The percentage yield was generally poor due to the recovery process. • Prodigiosin greatly reduced the viability of the breast cancer cell line (MDA-MB-231).

  3. Extraction and encapsulation of prodigiosin in chitosan microspheres for targeted drug delivery

    International Nuclear Information System (INIS)

    Dozie-Nwachukwu, S.O.; Danyuo, Y.; Obayemi, J.D.; Odusanya, O.S.; Malatesta, K.; Soboyejo, W.O.

    2017-01-01

    The encapsulation of drugs in polymeric materials has brought opportunities to the targeted delivery of chemotherapeutic agents. These polymeric delivery systems are capable of maximizing the therapeutic activity, as well as reducing the side effects of anti-cancer agents. Prodigiosin, a secondary metabolite extracted from the bacteria, Serratia marcescens, exhibits anti-cancer properties. Prodigiosin-loaded chitosan microspheres were prepared via water-in-oil (w/o) emulsion technique, using glutaraldehyde as a cross-linker. The morphologies of the microspheres were studied using scanning electron microscopy. The average sizes of the microspheres were between 40 μm and 60 μm, while the percentage yields ranged from 42 ± 2% to 55.5 ± 3%. The resulting encapsulation efficiencies were between 66.7 ± 3% and 90 ± 4%. The in-vitro drug release from the microspheres was characterized by zeroth order, first order and Higuchi and Korsmeyer-Peppas models. - Highlights: • Prodigiosin of ~ 92.8% purity was extracted from locally isolated Serratia marcescens. • This approach reduces the cost and ensure availability of drugs for cancer treatment. • High encapsulation efficiency which increased with increasing drug:polymer ratio • The percentage yield was generally poor due to the recovery process. • Prodigiosin greatly reduced the viability of the breast cancer cell line (MDA-MB-231).

  4. In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization.

    Science.gov (United States)

    Ndesendo, Valence M K; Choonara, Yahya E; Meyer, Leith C R; Kumar, Pradeep; Tomar, Lomas K; Tyagi, Charu; du Toit, Lisa C; Pillay, Viness

    2015-01-01

    The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery. Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3'-azido-3'-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings. There was a big deviation between the Tg of the polymeric caplet from the Tg's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012-0.332 mg/mL and 0.009-0.256 mg/mL for AZT and PSS over 1-28 d. The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.

  5. Progress and perspectives on targeting nanoparticles for brain drug delivery

    Institute of Scientific and Technical Information of China (English)

    Huile Gao

    2016-01-01

    Due to the ability of the blood–brain barrier(BBB) to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provides potential to overcome this problem. In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood–brain tumor barrier(BBTB), and nose-to-brain barrier. Delivery strategies are focused on overcoming the BBB, directly targeting diseased cells in the brain, and dual-targeted delivery. The major concerns and perspectives on constructing brain-targeted delivery systems are discussed.

  6. Progress and perspectives on targeting nanoparticles for brain drug delivery

    Directory of Open Access Journals (Sweden)

    Huile Gao

    2016-07-01

    Full Text Available Due to the ability of the blood–brain barrier (BBB to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provides potential to overcome this problem. In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood–brain tumor barrier (BBTB, and nose-to-brain barrier. Delivery strategies are focused on overcoming the BBB, directly targeting diseased cells in the brain, and dual-targeted delivery. The major concerns and perspectives on constructing brain-targeted delivery systems are discussed.

  7. Nasal Drug Delivery in Traditional Persian Medicine

    Science.gov (United States)

    Zarshenas, Mohammad Mehdi; Zargaran, Arman; Müller, Johannes; Mohagheghzadeh, Abdolali

    2013-01-01

    Background Over one hundred different pharmaceutical dosage forms have been recorded in literatures of Traditional Persian Medicine among which nasal forms are considerable. Objectives This study designed to derive the most often applied nasal dosage forms together with those brief clinical administrations. Materials and Methods In the current study remaining pharmaceutical manuscripts of Persia during 9th to 18th century AD have been studied and different dosage forms related to nasal application of herbal medicines and their therapeutic effects were derived. Results By searching through pharmaceutical manuscripts of medieval Persia, different nasal dosage forms involving eleven types related to three main groups are found. These types could be derived from powder, solution or liquid and gaseous forms. Gaseous form were classified into fumigation (Bakhoor), vapor bath (Enkebab), inhalation (Lakhlakheh), aroma agents (Ghalieh) and olfaction or smell (Shomoom). Nasal solutions were as drops (Ghatoor), nasal snuffing drops (Saoot) and liquid snuff formulations (Noshoogh). Powders were as nasal insufflation or snorting agents (Nofookh) and errhine or sternutator medicine (Otoos). Nasal forms were not applied only for local purposes. Rather systemic disorders and specially CNS complications were said to be a target for these dosage forms. Discussion While this novel type of drug delivery is known as a suitable substitute for oral and parenteral administration, it was well accepted and extensively mentioned in Persian medical and pharmaceutical manuscripts and other traditional systems of medicine as well. Accordingly, medieval pharmaceutical standpoints on nasal dosage forms could still be an interesting subject of study. Therefore, the current work can briefly show the pharmaceutical knowledge on nasal formulations in medieval Persia and clarify a part of history of traditional Persian pharmacy. PMID:24624204

  8. 3D printing applications for transdermal drug delivery.

    Science.gov (United States)

    Economidou, Sophia N; Lamprou, Dimitrios A; Douroumis, Dennis

    2018-06-15

    The role of two and three-dimensional printing as a fabrication technology for sophisticated transdermal drug delivery systems is explored in literature. 3D printing encompasses a family of distinct technologies that employ a virtual model to produce a physical object through numerically controlled apparatuses. The applicability of several printing technologies has been researched for the direct or indirect printing of microneedle arrays or for the modification of their surface through drug-containing coatings. The findings of the respective studies are presented. The range of printable materials that are currently used or potentially can be employed for 3D printing of transdermal drug delivery (TDD) systems is also reviewed. Moreover, the expected impact and challenges of the adoption of 3D printing as a manufacturing technique for transdermal drug delivery systems, are assessed. Finally, this paper outlines the current regulatory framework associated with 3D printed transdermal drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. DNA nanostructure-based drug delivery nanosystems in cancer therapy.

    Science.gov (United States)

    Wu, Dandan; Wang, Lei; Li, Wei; Xu, Xiaowen; Jiang, Wei

    2017-11-25

    DNA as a novel biomaterial can be used to fabricate different kinds of DNA nanostructures based on its principle of GC/AT complementary base pairing. Studies have shown that DNA nanostructure is a nice drug carrier to overcome big obstacles existing in cancer therapy such as systemic toxicity and unsatisfied drug efficacy. Thus, different types of DNA nanostructure-based drug delivery nanosystems have been designed in cancer therapy. To improve treating efficacy, they are also developed into more functional drug delivery nanosystems. In recent years, some important progresses have been made. The objective of this review is to make a retrospect and summary about these different kinds of DNA nanostructure-based drug delivery nanosystems and their latest progresses: (1) active targeting; (2) mutidrug co-delivery; (3) construction of stimuli-responsive/intelligent nanosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. A review on electrospun nanofibers for oral drug delivery

    Directory of Open Access Journals (Sweden)

    Abbas Akhgari

    2017-10-01

    Full Text Available Nowadays, polymer nanofibers have gained attention due to remarkable characteristics such as high porosity and large surface area to volume ratio. Among their fabrication methods, electrospinning technique has been attracted as a simple and reproducible approach. It is a versatile, simple and cost-effective technique for the production of continuous nanofibers with acceptable characteristics such as high porosity, high surface area to volume ratio, high loading capacity and encapsulation efficiency, delivery of multiple drugs, and enhancement of drug solubility. Due to these properties electrospun nanofibers have been extensively used for different biomedical applications including wound dressing, tissue engineering, enzyme immobilization, artificial organs, and drug delivery. Different synthetic and natural polymers have been successfully electrospun into ultrafine fibers. Using electrospun nanofibers as vehicles for oral drug delivery has been investigated in different release manners- fast, biphasic or sustained release. This article presents a review on application of electrospinning technique in oral drug delivery.

  11. Recent developments in oral lipid-based drug delivery

    DEFF Research Database (Denmark)

    Thomas, N.; Rades, T.; Müllertz, A.

    2013-01-01

    The increasing number of poorly water-soluble drugs in development in the pharmaceutical industry has sparked interest in novel drug delivery options such as lipid-based drug delivery systems (LbDDS). Several LbDDS have been marketed successfully and have shown superior and more reliable...... bioavailability compared to conventional formulations. However, some reluctance in the broader application of LbDDS still appears, despite the growing commercial interest in lipids as a drug delivery platform. This reluctance might at least in part be related to the complexity associated with the development...... and characterization of LbDDS. In particular, the lack of standardized test protocols can be identified as the major obstacles for the broader application of LbDDS. This review seeks to summarize recent approaches in the field of lipid-based drug delivery that try to elucidate some critical steps in their development...

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

    Science.gov (United States)

    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.

  13. Effect of thiol pendant conjugates on plasmid DNA binding, release, and stability of polymeric delivery vectors.

    Science.gov (United States)

    Bacalocostantis, Irene; Mane, Viraj P; Kang, Michael S; Goodley, Addison S; Muro, Silvia; Kofinas, Peter

    2012-05-14

    Polymers have attracted much attention as potential gene delivery vectors due to their chemical and structural versatility. However, several challenges associated with polymeric carriers, including low transfection efficiencies, insufficient cargo release, and high cytotoxicity levels have prevented clinical implementation. Strong electrostatic interactions between polymeric carriers and DNA cargo can prohibit complete cargo release within the cell. As a result, cargo DNA never reaches the cell's nucleus where gene expression takes place. In addition, highly charged cationic polymers have been correlated with high cytotoxicity levels, making them unsuitable carriers in vivo. Using poly(allylamine) (PAA) as a model, we investigated how pH-sensitive disulfide cross-linked polymer networks can improve the delivery potential of cationic polymer carriers. To accomplish this, we conjugated thiol-terminated pendant chains onto the primary amines of PAA using 2-iminothiolane, developing three new polymer vectors with 5, 13, or 20% thiol modification. Unmodified PAA and thiol-conjugated polymers were tested for their ability to bind and release plasmid DNA, their capacity to protect genetic cargo from enzymatic degradation, and their potential for endolysosomal escape. Our results demonstrate that polymer-plasmid complexes (polyplexes) formed by the 13% thiolated polymer demonstrate the greatest delivery potential. At high N/P ratios, all thiolated polymers (but not unmodified counterparts) were able to resist decomplexation in the presence of heparin, a negatively charged polysaccharide used to mimic in vivo polyplex-protein interactions. Further, all thiolated polymers exhibited higher buffering capacities than unmodified PAA and, therefore, have a greater potential for endolysosomal escape. However, 5 and 20% thiolated polymers exhibited poor DNA binding-release kinetics, making them unsuitable carriers for gene delivery. The 13% thiolated polymers, on the other hand

  14. A Controlled Drug-Delivery Experiment Using Alginate Beads

    Science.gov (United States)

    Farrell, Stephanie; Vernengo, Jennifer

    2012-01-01

    This paper describes a simple, cost-effective experiment which introduces students to drug delivery and modeling using alginate beads. Students produce calcium alginate beads loaded with drug and measure the rate of release from the beads for systems having different stir rates, geometries, extents of cross-linking, and drug molecular weight.…

  15. Development of a gastroretentive pulsatile drug delivery platform.

    Science.gov (United States)

    Thitinan, Sumalee; McConville, Jason T

    2012-04-01

    To develop a novel gastroretentive pulsatile drug delivery platform by combining the advantages of floating dosage forms for the stomach and pulsatile drug delivery systems. A gastric fluid impermeable capsule body was used as a vessel to contain one or more drug layer(s) as well as one or more lag-time controlling layer(s). A controlled amount of air was sealed in the innermost portion of the capsule body to reduce the overall density of the drug delivery platform, enabling gastric floatation. An optimal mass fill inside the gastric fluid impermeable capsule body enabled buoyancy in a vertical orientation to provide a constant surface area for controlled erosion of the lag-time controlling layer. The lag-time controlling layer consisted of a swellable polymer, which rapidly formed a gel to seal the mouth of capsule body and act as a barrier to gastric fluid ingress. By varying the composition of the lag-time controlling layer, it was possible to selectively program the onset of the pulsatile delivery of a drug. This new delivery platform offers a new method of delivery for a variety of suitable drugs targeted in chronopharmaceutical therapy. This strategy could ultimately improve drug efficacy and patient compliance, and reduce harmful side effects by scaling back doses of drug administered. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  16. Synthesis and characterization of novel dual-responsive nanogels and their application as drug delivery systems

    Science.gov (United States)

    Peng, Jinrong; Qi, Tingting; Liao, Jinfeng; Fan, Min; Luo, Feng; Li, He; Qian, Zhiyong

    2012-03-01

    In this study, a temperature/pH dual-response nanogel based on NIPAm, MAA, and PEGMA was synthesized via emulsion polymerization and characterized by 1H-NMR, FT-IR, TEM and DLS. By introducing a novel initiator, through which PEG-AIBN-PEG was synthesized, it was revealed that the PEG segments from PEG-AIBN-PEG with a dosage of initiator had a significant influence over the macro-state and stability of the nanogels. In order to optimize the feeding prescription for better application as a drug delivery system, the effect of the co-monomer contents on the response to stimuli (temperature and pH value) and cytotoxicity of the nanogels has been studied in detail. The results demonstrated that the responsiveness, reversibility and volume phase transition critical value of the nanogels could be controlled by adjusting the feeding ratio of the co-monomers in the synthesis process. MTT assay results revealed that nanogels with appropriate compositions showed good biocompatibility and relatively low toxicity. Most importantly, by studying the drug loading behavior, it was found that the dimensions of the drug molecules had a considerable influence on the drug loading efficiency and loading capacity of the nanogels, and that the mechanism by which drug molecule sizes influence the drug loading behavior of nanogels needs further investigation. The results indicated that such PNMP nanogels might have potential applications in drug delivery and other medical applications, but that the drug loading mechanism must be further developed.

  17. Multifunctional quantum dots and liposome complexes in drug delivery

    Science.gov (United States)

    Wang, Qi; Chao, Yimin

    2018-01-01

    Incorporating both diagnostic and therapeutic functions into a single nanoscale system is an effective modern drug delivery strategy. Combining liposomes with semiconductor quantum dots (QDs) has great potential to achieve such dual functions, referred to in this review as a liposomal QD hybrid system (L-QD). Here we review the recent literature dealing with the design and application of L-QD for advances in bio-imaging and drug delivery. After a summary of L-QD synthesis processes and evaluation of their properties, we will focus on their multifunctional applications, ranging from in vitro cell imaging to theranostic drug delivery approaches. PMID:28866655

  18. Multifunctional quantum dots and liposome complexes in drug delivery.

    Science.gov (United States)

    Wang, Qi; Chao, Yi-Min

    2017-09-03

    Incorporating both diagnostic and therapeutic functions into a single nanoscale system is an effective modern drug delivery strategy. Combining liposomes with semiconductor quantum dots (QDs) has great potential to achieve such dual functions, referred to in this review as a liposomal QD hybrid system (L-QD). Here we review the recent literature dealing with the design and application of L-QD for advances in bio-imaging and drug delivery. After a summary of L-QD synthesis processes and evaluation of their properties, we will focus on their multifunctional applications, ranging from in vitro cell imaging to theranostic drug delivery approaches.

  19. Porous silicon advances in drug delivery and immunotherapy.

    Science.gov (United States)

    Savage, David J; Liu, Xuewu; Curley, Steven A; Ferrari, Mauro; Serda, Rita E

    2013-10-01

    Biomedical applications of porous silicon include drug delivery, imaging, diagnostics and immunotherapy. This review summarizes new silicon particle fabrication techniques, dynamics of cellular transport, advances in the multistage vector approach to drug delivery, and the use of porous silicon as immune adjuvants. Recent findings support superior therapeutic efficacy of the multistage vector approach over single particle drug delivery systems in mouse models of ovarian and breast cancer. With respect to vaccine development, multivalent presentation of pathogen-associated molecular patterns on the particle surface creates powerful platforms for immunotherapy, with the porous matrix able to carry both antigens and immune modulators. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. A study on nanodiamond-based drug delivery system

    International Nuclear Information System (INIS)

    Li Jing; Zhang Xiaoyong; Zhu Ying; Li Wenxin; Huang Qing

    2010-01-01

    A multifunctional drug delivery system based on nanodiamonds (NDs) has been developed. FITC, HCPT and TF were absorbed on NDs successively to form the multifunctional complex. The NDs and ND complex samples were characterized by TEM, FR-IR and UV-V. The results indicated that this drug delivery system is a high loading system. Efficacy of the drug delivery system on Hela cell was evaluated with MTT assays and fluorescence microscopy. The results show that multifunction of the NDs complex include fluorescence, targeting and high efficacy. (authors)

  1. 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.

  2. 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.

  3. Polymeric nanoparticles – a novel solution for delivery of antimicrobial agents

    Directory of Open Access Journals (Sweden)

    Grzegorz Michalak

    2016-04-01

    Full Text Available The increased prevalence of antibiotic-resistant pathogens requires additional efforts to develop new antimicrobial agents and alternative methods to prevent and treat infections. In response to this challenge, a variety of nanotechnology-based tools are currently being designed and thoroughly investigated. To date, a considerable number of studies have reported increased activity of antibiotic-conjugated polymeric nanoparticles against bacteria and fungi associated with various infections, including those caused by drug-resistant pathogens. Importantly, high biocompatibility of these structures coupled with enhanced biological activity and improved pharmacokinetic properties supports the potential of these nanosystems as new tools to treat infections. In this review, we summarize the synthesis of polymer-based nanoparticles and describe their mechanism of action. We also highlight the recent advances in the application of antibiotic-conjugated polymeric nanoparticles as novel antimicrobial agents.

  4. Synthesis of an amphiphilic dendrimer-like block copolymer and its application on drug delivery

    KAUST Repository

    Wang, Shuaipeng

    2014-10-27

    Dendrimer-like amphiphilic copolymer is a kind of three-dimensional spherical structure polymer. An amphiphilic dendrimer-like diblock copolymer, PEEGE-G2-b-PEO(OH)12, constituted of a hydrophobic poly(ethoxyethyl glycidol ether) inner core and a hydrophilic poly(ethylene oxide) outer layer, has been successfully synthesized by the living anionic ring-opening polymerization method. The intermediates and targeted products were characterized with 1H NMR spectroscopy and gel permeation chromatography. The application on drug delivery of dendrimer-like diblock copolymer PEEGE-G2-b-PEO(OH)12 using DOX as a model drug was also studied. The drug loading content and encapsulation efficiency were found at 13.07% and 45.75%, respectively. In vitro release experiment results indicated that the drug-loaded micelles exhibited a sustained release behavior under acidic media.

  5. Nonlinearities in Drug Release Process from Polymeric Microparticles: Long-Time-Scale Behaviour

    Directory of Open Access Journals (Sweden)

    Elena Simona Bacaita

    2012-01-01

    Full Text Available A theoretical model of the drug release process from polymeric microparticles (a particular type of polymer matrix, through dispersive fractal approximation of motion, is built. As a result, the drug release process takes place through cnoidal oscillations modes of a normalized concentration field. This indicates that, in the case of long-time-scale evolutions, the drug particles assemble in a lattice of nonlinear oscillators occur macroscopically, through variations of drug concentration. The model is validated by experimental results.

  6. Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications

    Science.gov (United States)

    Kalomiraki, Marina; Thermos, Kyriaki; Chaniotakis, Nikos A

    2016-01-01

    Dendrimers are large polymeric structures with nanosize dimensions (1–10 nm) and unique physicochemical properties. The major advantage of dendrimers compared with linear polymers is their spherical-shaped structure. During synthesis, the size and shape of the dendrimer can be customized and controlled, so the finished macromolecule will have a specific “architecture” and terminal groups. These characteristics will determine its suitability for drug delivery, diagnostic imaging, and as a genetic material carrier. This review will focus initially on the unique properties of dendrimers and their use in biomedical applications, as antibacterial, antitumor, and diagnostic agents. Subsequently, emphasis will be given to their use in drug delivery for ocular diseases. PMID:26730187

  7. Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications

    Directory of Open Access Journals (Sweden)

    Kalomiraki M

    2015-12-01

    Full Text Available Marina Kalomiraki,1 Kyriaki Thermos,2 Nikos A Chaniotakis1 1Laboratory of Analytical Chemistry, Department of Chemistry, 2Department of Pharmacology, School of Medicine, University of Crete Voutes, Heraklion, Greece Abstract: Dendrimers are large polymeric structures with nanosize dimensions (1–10 nm and unique physicochemical properties. The major advantage of dendrimers compared with linear polymers is their spherical-shaped structure. During synthesis, the size and shape of the dendrimer can be customized and controlled, so the finished macromolecule will have a specific “architecture” and terminal groups. These characteristics will determine its suitability for drug delivery, diagnostic imaging, and as a genetic material carrier. This review will focus initially on the unique properties of dendrimers and their use in biomedical applications, as antibacterial, antitumor, and diagnostic agents. Subsequently, emphasis will be given to their use in drug delivery for ocular diseases. Keywords: nanoparticles, ocular diseases, encapsulation, macromolecule, diagnostic agent

  8. Fractional laser-assisted drug delivery

    DEFF Research Database (Denmark)

    Taudorf, Elisabeth Hjardem; Lerche, C.M.; Erlendsson, A M

    2016-01-01

    BACKGROUND AND OBJECTIVE: Ablative fractional laser (AFXL) facilitates delivery of topical methotrexate (MTX). This study investigates impact of laser-channel depth on topical MTX-delivery. MATERIALS AND METHODS: MTX (1% [w/v]) diffused for 21 hours through AFXL-exposed porcine skin in in vitro F...

  9. Elastic liposomes as novel carriers: recent advances in drug delivery

    Directory of Open Access Journals (Sweden)

    Hussain A

    2017-07-01

    Full Text Available Afzal Hussain,1,2 Sima Singh,1 Dinesh Sharma,3 Thomas J Webster,4 Kausar Shafaat,2 Abdul Faruk5 1Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India; 2Faculty of Pharmacy, Sachchidananda Sinha College, Aurangabad, Bihar, India; 3Zifam Pyrex Myanmar Co. Ltd., Yangon, Myanmar; 4Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 5Department of Pharmaceutical Sciences, Hemwati Nandan Bahuguna Garhwal University, Srinagar, Uttarakhand, India Abstract: Elastic liposomes (EL are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields. Keywords: elastic liposomes, drug delivery, topical, transdermal, enhanced delivery 

  10. Magnetic microspheres as magical novel drug delivery system: A review

    Directory of Open Access Journals (Sweden)

    Satinder Kakar

    2013-01-01

    Full Text Available Magnetic microspheres hold great promise for reaching the goal of controlled and site specific drug delivery. Magnetic microspheres as an alternative to traditional radiation methods which uses highly penetrating radiations that is absorbed throughout the body. Its use is limited by toxicity and side effects. Now days, several targeted treatment systems including magnetic field, electric field, ultrasound, temperature, UV light and mechanical force are being used in many disease treatments (e.g. cancer, nerve damage, heart and artery, anti-diabetic, eye and other medical treatments. Among them, the magnetic targeted drug delivery system is one of the most attractive and promising strategy for delivering the drug to the specified site. Magnetically controlled drug targeting is one of the various possible ways of drug targeting. This technology is based on binding establish anticancer drug with ferrofluid that concentrate the drug in the area of interest (tumor site by means of magnetic fields. There has been keen interest in the development of a magnetically target drug delivery system. These drug delivery systems aim to deliver the drug at a rate directed by the needs of the body during the period of treatment, and target the activity entity to the site of action. Magnetic microspheres were developed to overcome two major problems encountered in drug targeting namely: RES clearance and target site specificity.

  11. Inhaled Micro/Nanoparticulate Anticancer Drug Formulations: An Emerging Targeted Drug Delivery Strategy for Lung Cancers.

    Science.gov (United States)

    Islam, Nazrul; Richard, Derek

    2018-05-24

    Local delivery of drug to the target organ via inhalation offers enormous benefits in the management of many diseases. Lung cancer is the most common of all cancers and it is the leading cause of death worldwide. Currently available treatment systems (intravenous or oral drug delivery) are not efficient in accumulating the delivered drug into the target tumor cells and are usually associated with various systemic and dose-related adverse effects. The pulmonary drug delivery technology would enable preferential accumulation of drug within the cancer cell and thus be superior to intravenous and oral delivery in reducing cancer cell proliferation and minimising the systemic adverse effects. Site-specific drug delivery via inhalation for the treatment of lung cancer is both feasible and efficient. The inhaled drug delivery system is non-invasive, produces high bioavailability at low dose and avoids first pass metabolism of the delivered drug. Various anticancer drugs including chemotherapeutics, proteins and genes have been investigated for inhalation in lung cancers with significant outcomes. Pulmonary delivery of drugs from dry powder inhaler (DPI) formulation is stable and has high patient compliance. Herein, we report the potential of pulmonary drug delivery from dry powder inhaler (DPI) formulations inhibiting lung cancer cell proliferation at very low dose with reduced unwanted adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Targeted drug delivery and penetration into solid tumors.

    Science.gov (United States)

    Corti, Angelo; Pastorino, Fabio; Curnis, Flavio; Arap, Wadih; Ponzoni, Mirco; Pasqualini, Renata

    2012-09-01

    Delivery and penetration of chemotherapeutic drugs into tumors are limited by a number of factors related to abnormal vasculature and altered stroma composition in neoplastic tissues. Coupling of chemotherapeutic drugs with tumor vasculature-homing peptides or administration of drugs in combination with biological agents that affect the integrity of the endothelial lining of tumor vasculature is an appealing strategy to improve drug delivery to tumor cells. Promising approaches to achieve this goal are based on the use of Asn-Gly-Arg (NGR)-containing peptides as ligands for drug delivery and of NGR-TNF, a peptide-tumor necrosis factor-α fusion protein that selectively alters drug penetration barriers and that is currently tested in a randomized Phase III trial in patients with malignant pleural mesothelioma. © 2011 Wiley Periodicals, Inc.

  13. Buccal Drug Delivery System: A Review

    OpenAIRE

    Parth S. Patel; Ashish M. Parmar; Nilang S. Doshi; Hardik V. Patel; Raxit R. Patel; Chetan Nayee

    2013-01-01

    Bioadhesion can be defined as a phenomenon of interfacial molecular attractive forces in the midst of the surfaces of the biological substrate and the natural or synthetic polymers, which allows the polymer to adhere to the biological surface for an extended period of time. Bioadhesive polymeric systems have been used since extent in the development of products for various biomedical applications which include denture adhesives and surgical glue.Considerable attention has been focused in rece...

  14. Atopic Dermatitis: Drug Delivery Approaches in Disease Management.

    Science.gov (United States)

    Lalan, Manisha; Baweja, Jitendra; Misra, Ambikanandan

    2015-01-01

    In this review, we describe the very basic of atopic dermatitis (AD), the established management strategies, and the advances in drug delivery approaches for successful therapeutic outcomes. The multifactorial pathophysiology of AD has given rise to the clinician's paradigm of topical and systemic therapy and potential combinations. However, incomplete remission of skin disorders like AD is a major challenge to be overcome. Recurrence is thought to be due to genetic and immunological etiologies and shortcomings in drug delivery. This difficulty has sparked research in nanocarrier-based delivery approaches as well as molecular biology-inspired stratagems to deal with the immunological imbalance and to address insufficiencies of delivery propositions. In this review, we assess various novel drug delivery strategies in terms of their success and utility. We present a brief compilation and assessment of management modalities to sensitize the readers to therapeutic scenario in AD.

  15. Design of interior-functionalized fully acetylated dendrimers for anticancer drug delivery.

    Science.gov (United States)

    Hu, Jingjing; Su, Yunzhang; Zhang, Hongfeng; Xu, Tongwen; Cheng, Yiyun

    2011-12-01

    In this study, dendrimers was synthesized by introducing functional groups into the interior pockets of fully acetylated dendrimers. NMR techniques including COSY and 2D-NOESY revealed the molecular structures of the synthesized dendrimers and the encapsulation of guest molecule such as methotrexate within their interior pockets. The synthesized polymeric nanocarriers showed much lower cytotoxicity on two cell lines than cationic dendrimers, and exhibited better performance than fully acetylated dendrimers in the sustained release of methotrexate. The results provided a new strategy in the design of non-toxic dendrimers with high performance in the delivery of anti-cancer drugs for clinical applications. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Drug Combination Synergy in Worm-like Polymeric Micelles Improves Treatment Outcome for Small Cell and Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Wan, Xiaomeng; Min, Yuanzeng; Bludau, Herdis; Keith, Andrew; Sheiko, Sergei S; Jordan, Rainer; Wang, Andrew Z; Sokolsky-Papkov, Marina; Kabanov, Alexander V

    2018-03-27

    Nanoparticle-based systems for concurrent delivery of multiple drugs can improve outcomes of cancer treatments, but face challenges because of differential solubility and fairly low threshold for incorporation of many drugs. Here we demonstrate that this approach can be used to greatly improve the treatment outcomes of etoposide (ETO) and platinum drug combination ("EP/PE") therapy that is the backbone for treatment of prevalent and deadly small cell lung cancer (SCLC). A polymeric micelle system based on amphiphilic block copolymer poly(2-oxazoline)s (POx) poly(2-methyl-2-oxazoline- block-2-butyl-2-oxazoline- block-2-methyl-2-oxazoline) (P(MeOx- b-BuOx- b-MeOx) is used along with an alkylated cisplatin prodrug to enable co-formulation of EP/PE in a single high-capacity vehicle. A broad range of drug mixing ratios and exceptionally high two-drug loading of over 50% wt. drug in dispersed phase is demonstrated. The highly loaded POx micelles have worm-like morphology, unprecedented for drug loaded polymeric micelles reported so far, which usually form spheres upon drug loading. The drugs co-loading in the micelles result in a slowed-down release, improved pharmacokinetics, and increased tumor distribution of both drugs. A superior antitumor activity of co-loaded EP/PE drug micelles compared to single drug micelles or their combination as well as free drug combination was demonstrated using several animal models of SCLC and non-small cell lung cancer.

  17. 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

  18. Responsive Boronic Acid-Decorated (Co)polymers: From Glucose Sensors to Autonomous Drug Delivery.

    Science.gov (United States)

    Vancoillie, Gertjan; Hoogenboom, Richard

    2016-10-19

    Boronic acid-containing (co)polymers have fascinated researchers for decades, garnering attention for their unique responsiveness toward 1,2- and 1,3-diols, including saccharides and nucleotides. The applications of materials that exert this property are manifold including sensing, but also self-regulated drug delivery systems through responsive membranes or micelles. In this review, some of the main applications of boronic acid containing (co)polymers are discussed focusing on the role of the boronic acid group in the response mechanism. We hope that this summary, which highlights the importance and potential of boronic acid-decorated polymeric materials, will inspire further research within this interesting field of responsive polymers and polymeric materials.

  19. Responsive Boronic Acid-Decorated (Copolymers: From Glucose Sensors to Autonomous Drug Delivery

    Directory of Open Access Journals (Sweden)

    Gertjan Vancoillie

    2016-10-01

    Full Text Available Boronic acid-containing (copolymers have fascinated researchers for decades, garnering attention for their unique responsiveness toward 1,2- and 1,3-diols, including saccharides and nucleotides. The applications of materials that exert this property are manifold including sensing, but also self-regulated drug delivery systems through responsive membranes or micelles. In this review, some of the main applications of boronic acid containing (copolymers are discussed focusing on the role of the boronic acid group in the response mechanism. We hope that this summary, which highlights the importance and potential of boronic acid-decorated polymeric materials, will inspire further research within this interesting field of responsive polymers and polymeric materials.

  20. Nanomaterial-based drug delivery carriers for cancer therapy

    CERN Document Server

    Feng, Tao

    2017-01-01

    This brief summarizes different types of organic and inorganic nanomaterials for drug delivery in cancer therapy. It highlights that precisely designed nanomaterials will be the next-generation therapeutic agents for cancer treatment.

  1. Applications of nanodiamonds in drug delivery and catalysis

    KAUST Repository

    Moosa, Basem; Fhayli, Karim; Li, Song; Julfakyan, Khachatur; Ezzeddine, Alaa; Khashab, Niveen M.

    2014-01-01

    The interest of researchers in utilizing nanomaterials as carriers for a wide spectrum of molecules has exploded in the last two decades. Nanodiamonds are one class of carbon-based nanomaterials that have emerged as promising drug delivery vehicles

  2. A remotely operated drug delivery system with dose control

    KAUST Repository

    Yi, Ying; Kosel, Jü rgen

    2017-01-01

    include an effective actuation stimulus and a controllable dose release mechanism. This work focuses on remotely powering an implantable drug delivery system and providing a high degree of control over the released dose. This is accomplished by integration

  3. A Microfluidic Ion Pump for In Vivo Drug Delivery

    KAUST Repository

    Uguz, Ilke

    2017-05-15

    Implantable devices offer an alternative to systemic delivery of drugs for the treatment of neurological disorders. A microfluidic ion pump (µFIP), capable of delivering a drug without the solvent through electrophoresis, is developed. The device is characterized in vitro by delivering γ-amino butyric acid to a target solution, and demonstrates low-voltage operation, high drug-delivery capacity, and high ON/OFF ratio. It is also demonstrated that the device is suitable for cortical delivery in vivo by manipulating the local ion concentration in an animal model and altering neural behavior. These results show that µFIPs represent a significant step forward toward the development of implantable drug-delivery systems.

  4. A smart pill for drug delivery with sensing capabilities.

    Science.gov (United States)

    Goffredo, R; Accoto, D; Santonico, M; Pennazza, G; Guglielmelli, E

    2015-08-01

    In this paper a novel system for local drug delivery is described. The actuation principle of the micropump used for drug delivery relies on the electrolysis of a water-based solution, which is separated from a drug reservoir by an elastic membrane. The electrolytically produced gases pressurize the electrolytic solution reservoir, causing the deflection of the elastic membrane. Such deflection, in turn, forces the drug out of its reservoir through a nozzle. The proposed system is integrated in a swallowable capsule, equipped with an impedance sensor useful to acquire information on the physiological conditions of the tissue. Such information can be used to control pump activation.

  5. Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation

    Directory of Open Access Journals (Sweden)

    Reshmy Rajan

    2011-01-01

    Full Text Available Transdermal administration of drugs is generally limited by the barrier function of the skin. Vesicular systems are one of the most controversial methods for transdermal delivery of active substances. The interest in designing transdermal delivery systems was relaunched after the discovery of elastic vesicles like transferosomes, ethosomes, cubosomes, phytosomes, etc. This paper presents the composition, mechanisms of penetration, manufacturing and characterization methods of transferosomes as transdermal delivery systems of active substances. For a drug to be absorbed and distributed into organs and tissues and eliminated from the body, it must pass through one or more biological membranes/barriers at various locations. Such a movement of drug across the membrane is called as drug transport. For the drugs to be delivered to the body, they should cross the membranous barrier. The concept of these delivery systems was designed in an attempt to concentrate the drug in the tissues of interest, while reducing the amount of drug in the remaining tissues. Hence, surrounding tissues are not affected by the drug. In addition, loss of drug does not happen due to localization of drug, leading to get maximum efficacy of the medication. Therefore, the phospholipid based carrier systems are of considerable interest in this era.

  6. TRANSDERMAL DRUG DELIVERY AND METHODS TO ENHANCE IT

    Directory of Open Access Journals (Sweden)

    E. G. Kuznetsova

    2016-01-01

    Full Text Available The paper presents the common methods employed in recent years for enhancing transdermal delivery of drug substances when applying transdermal therapeutic delivery systems. The chemical, physical and mechanical methods to enhance the transport of macromolecular compounds through the skin are considered in details. 

  7. Adamantane in Drug Delivery Systems and Surface Recognition

    OpenAIRE

    Adela Štimac; Marina Šekutor; Kata Mlinarić-Majerski; Leo Frkanec; Ruža Frkanec

    2017-01-01

    The adamantane moiety is widely applied in design and synthesis of new drug delivery systems and in surface recognition studies. This review focuses on liposomes, cyclodextrins, and dendrimers based on or incorporating adamantane derivatives. Our recent concept of adamantane as an anchor in the lipid bilayer of liposomes has promising applications in the field of targeted drug delivery and surface recognition. The results reported here encourage the development of novel adamantane-based struc...

  8. 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)

  9. Natural polymers, gums and mucilages as excipients in drug delivery.

    Science.gov (United States)

    Kumar, Shobhit; Gupta, Satish Kumar

    2012-01-01

    Use of natural polymers, gums and mucilages in drug delivery systems has been weighed down by the synthetic materials. Natural based excipients offered advantages such as non-toxicity, less cost and abundantly availablity. Aqueous solubility of natural excipients plays an important role in their selection for designing immediate, controlled or sustained release formulations. This review article provide an overview of natural gum, polymers and mucilages as excipients in dosage forms as well as novel drug delivery systems.

  10. Recent advances on smart TiO2 nanotube platforms for sustainable drug delivery applications

    Directory of Open Access Journals (Sweden)

    Wang Q

    2016-12-01

    Full Text Available Qun Wang,1,2,* Jian-Ying Huang,2,* Hua-Qiong Li,3,4 Allan Zi-Jian Zhao,4 Yi Wang,4 Ke-Qin Zhang,2,5 Hong-Tao Sun,1 Yue-Kun Lai,2,5 1College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 2National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 3Institute of Biomaterials and Engineering, Wenzhou Medical University, 4Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Sciences, Wenzhou, 5Research Center of Cooperative Innovation for Functional Organic/Polymer Material Micro/Nanofabrication, Suzhou, People’s Republic of China *These authors contributed equally to this work Abstract: To address the limitations of traditional drug delivery, TiO2 nanotubes (TNTs are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future. Keywords: TiO2 nanotubes, electrochemical anodization, modification, stimulated drug delivery, drug-releasing implant

  11. 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.

  12. Exploiting Specific Interactions toward Next-Generation Polymeric Drug Transporters

    NARCIS (Netherlands)

    Wieczorek, Sebastian; Krause, Eberhard; Hackbarth, Steffen; Roeder, Beate; Hirsch, Anna K. H.; Boerner, Hans G.

    2013-01-01

    A generic method describes advanced tailoring of polymer drug carriers based on polymer-block-peptides. Combinatorial means are used to select suitable peptide segments to specifically complex small-molecule drugs. The resulting specific drug formulation agents render insoluble drugs water-soluble

  13. Naturapolyceutics: The Science of Utilizing Natural Polymers for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Ndidi C. Ngwuluka

    2014-05-01

    Full Text Available Naturapolyceutics defines the emerging science and technology platform that blends natural polymers and pharmaceutics for the design and development of drug delivery systems. Natural polymers due to their biological properties, sustainability, chemical flexibility, human and eco-friendliness are promising in this field. As drug delivery advances, there will be need for more polymers. Given that polymers utilized in pharmaceuticals require regulatory approval, robust processes are undertaken to facilitate the production of pharmaceutical grade natural polymers. This review provides insight into the processes—extraction, purification, modifications and characterizations—involved in the eventual utilization of natural polymers for drug delivery. The versatility of natural polymers and particularly modified natural polymers in targeted drug delivery, micro-/nano-drug delivery, theranostics, BioMEMs and generally in research and development of highly efficient, safe and quality products is demonstrated. Natural polymers are polymers of today and tomorrow. Therefore, the shift to undertake training, extensive research and subsequent commercialization of more natural polymers—novel and underutilized—for drug delivery is now!

  14. Ophthalmic Drug Delivery Systems for Antibiotherapy—A Review

    Science.gov (United States)

    Dubald, Marion; Bourgeois, Sandrine; Andrieu, Véronique; Fessi, Hatem

    2018-01-01

    The last fifty years, ophthalmic drug delivery research has made much progress, challenging scientists about the advantages and limitations of this drug delivery approach. Topical eye drops are the most commonly used formulation in ocular drug delivery. Despite the good tolerance for patients, this topical administration is only focus on the anterior ocular diseases and had a high precorneal loss of drugs due to the tears production and ocular barriers. Antibiotics are popularly used in solution or in ointment for the ophthalmic route. However, their local bioavailability needs to be improved in order to decrease the frequency of administrations and the side effects and to increase their therapeutic efficiency. For this purpose, sustained release forms for ophthalmic delivery of antibiotics were developed. This review briefly describes the ocular administration with the ocular barriers and the currently topical forms. It focuses on experimental results to bypass the limitations of ocular antibiotic delivery with new ocular technology as colloidal and in situ gelling systems or with the improvement of existing forms as implants and contact lenses. Nanotechnology is presently a promising drug delivery way to provide protection of antibiotics and improve pathway through ocular barriers and deliver drugs to specific target sites. PMID:29342879

  15. Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

    Science.gov (United States)

    Dhote, Vinod; Bhatnagar, Punit; Mishra, Pradyumna K.; Mahajan, Suresh C.; Mishra, Dinesh K.

    2012-01-01

    The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application. PMID:22396901

  16. Ophthalmic Drug Delivery Systems for Antibiotherapy—A Review

    Directory of Open Access Journals (Sweden)

    Marion Dubald

    2018-01-01

    Full Text Available The last fifty years, ophthalmic drug delivery research has made much progress, challenging scientists about the advantages and limitations of this drug delivery approach. Topical eye drops are the most commonly used formulation in ocular drug delivery. Despite the good tolerance for patients, this topical administration is only focus on the anterior ocular diseases and had a high precorneal loss of drugs due to the tears production and ocular barriers. Antibiotics are popularly used in solution or in ointment for the ophthalmic route. However, their local bioavailability needs to be improved in order to decrease the frequency of administrations and the side effects and to increase their therapeutic efficiency. For this purpose, sustained release forms for ophthalmic delivery of antibiotics were developed. This review briefly describes the ocular administration with the ocular barriers and the currently topical forms. It focuses on experimental results to bypass the limitations of ocular antibiotic delivery with new ocular technology as colloidal and in situ gelling systems or with the improvement of existing forms as implants and contact lenses. Nanotechnology is presently a promising drug delivery way to provide protection of antibiotics and improve pathway through ocular barriers and deliver drugs to specific target sites.

  17. Micro-Fluidic Device for Drug Delivery

    Science.gov (United States)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2014-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  18. Targeted electrohydrodynamic printing for micro-reservoir drug delivery systems

    International Nuclear Information System (INIS)

    Hwang, Tae Heon; Kim, Jin Bum; Yang, Da Som; Ryu, WonHyoung; Park, Yong-il

    2013-01-01

    Microfluidic drug delivery systems consisting of a drug reservoir and microfluidic channels have shown the possibility of simple and robust modulation of drug release rate. However, the difficulty of loading a small quantity of drug into drug reservoirs at a micro-scale limited further development of such systems. Electrohydrodynamic (EHD) printing was employed to fill micro-reservoirs with controlled amount of drugs in the range of a few hundreds of picograms to tens of micrograms with spatial resolution of as small as 20 µm. Unlike most EHD systems, this system was configured in combination with an inverted microscope that allows in situ targeting of drug loading at micrometer scale accuracy. Methylene blue and rhodamine B were used as model drugs in distilled water, isopropanol and a polymer solution of a biodegradable polymer and dimethyl sulfoxide (DMSO). Also tetracycline-HCl/DI water was used as actual drug ink. The optimal parameters of EHD printing to load an extremely small quantity of drug into microscale drug reservoirs were investigated by changing pumping rates, the strength of an electric field and drug concentration. This targeted EHD technique was used to load drugs into the microreservoirs of PDMS microfluidic drug delivery devices and their drug release performance was demonstrated in vitro. (paper)

  19. Celecoxib coupled to dextran via a glutamic acid linker yields a polymeric prodrug suitable for colonic delivery.

    Science.gov (United States)

    Lee, Yonghyun; Kim, Jungyun; Kim, Wooseong; Nam, Joon; Jeong, Seongkeun; Lee, Sunyoung; Yoo, Jin-Wook; Kim, Min-Soo; Jung, Yunjin

    2015-01-01

    Celecoxib, a selective cyclooxygenase-2 inhibitor, is potentially useful for the treatment of colonic diseases such as colorectal cancer and colitis. However, the cardiovascular toxicity of celecoxib limits its routine use in the clinic. Generally, colon-specific delivery of a drug both increases the therapeutic availability in the large intestine and decreases the systemic absorption of the drug, most likely resulting in enhanced therapeutic effects against colonic diseases such as colitis and reduced systemic side effects. To develop a colon-specific prodrug of celecoxib that could reduce its cardiovascular toxicity and improve its therapeutic activity, dextran-glutamic acid-celecoxib conjugate (glutam-1-yl celecoxib-dextran ester [G1CD]) was prepared and evaluated. While stable in pH 1.2 and 6.8 buffer solutions and small-intestinal contents, G1CD efficiently released celecoxib in cecal contents. Oral administration of G1CD to rats delivered a larger amount of celecoxib to the large intestine than free celecoxib. G1CD prevented the systemic absorption of celecoxib and did not decrease the serum level of 6-ketoprostaglandin F1α, an inverse indicator of cardiovascular toxicity of celecoxib. Collectively, G1CD may be a polymeric colon-specific celecoxib prodrug with therapeutic and toxicological advantages.

  20. Using exosomes, naturally-equipped nanocarriers, for drug delivery.

    Science.gov (United States)

    Batrakova, Elena V; Kim, Myung Soo

    2015-12-10

    Exosomes offer distinct advantages that uniquely position them as highly effective drug carriers. Comprised of cellular membranes with multiple adhesive proteins on their surface, exosomes are known to specialize in cell-cell communications and provide an exclusive approach for the delivery of various therapeutic agents to target cells. In addition, exosomes can be amended through their parental cells to express a targeting moiety on their surface, or supplemented with desired biological activity. Development and validation of exosome-based drug delivery systems are the focus of this review. Different techniques of exosome isolation, characterization, drug loading, and applications in experimental disease models and clinic are discussed. Exosome-based drug formulations may be applied to a wide variety of disorders such as cancer, various infectious, cardiovascular, and neurodegenerative disorders. Overall, exosomes combine benefits of both synthetic nanocarriers and cell-mediated drug delivery systems while avoiding their limitations. Published by Elsevier B.V.

  1. Engineering Microneedle Patches for Vaccination and Drug Delivery to Skin.

    Science.gov (United States)

    Prausnitz, Mark R

    2017-06-07

    Microneedle patches (MNPs) contain arrays of solid needles measuring hundreds of microns in length that deliver drugs and vaccines into skin in a painless, easy-to-use manner. Optimal MNP design balances multiple interdependent parameters that determine mechanical strength, skin-insertion reliability, drug delivery efficiency, painlessness, manufacturability, and other features of MNPs that affect their performance. MNPs can be made by adapting various microfabrication technologies for delivery of small-molecule drugs, biologics, and vaccines targeted to the skin, which can have pharmacokinetic and immunologic advantages. A small number of human clinical trials, as well as a large and growing market for MNP products for cosmetics, indicate that MNPs can be used safely, efficaciously, and with strong patient acceptance. More advanced clinical trials and commercial-scale manufacturing will facilitate development of MNPs to realize their potential to dramatically increase patient access to otherwise-injectable drugs and to improve drug performance via skin delivery.

  2. 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.

  3. MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model

    Directory of Open Access Journals (Sweden)

    Vinh NQ

    2015-06-01

    saline controls. Our results suggest that Gd-DTPA/DACHPt-loaded micelles are a promising approach for effective diagnosis and treatment of advanced HCC. Keywords: Gd-DTPA/DACHPt-loaded micelles, polymeric micelles, drug delivery, hepatocellular carcinoma

  4. Cytotoxicity and Acute Gastrointestinal Toxicity of Bacterial Cellulose-Poly (acrylamide-sodium acrylate Hydrogel: A Carrier for Oral Drug Delivery

    Directory of Open Access Journals (Sweden)

    Manisha Pandey 1,2 * , Hira Choudhury 1, Mohd Cairul Iqbal Mohd Amin 2

    2016-12-01

    Full Text Available Background: Preliminary safety evaluation of polymer intended to use as drug delivery carrier is essential. Methods: In this study polyacrylamide grafted bacterial cellulose (BC/AM hydrogel was prepared by microwave irradiation initiated free radical polymerization. The synthesized hydrogel was subjected to in vitro cytotoxicity and acute gastrointestinal toxicity studies to evaluate its biological safety as potential oral drug delivery carrier. Results: The results indicate that hydrogel was non cytotoxic and did not show any histopathological changes in GI tract after a high dose of oral administration. Conclusion: The results revealed that hydrogel composed of bacterial cellulose and polyacrylamide is safe as oral drug delivery carrier.

  5. Computational and experimental model of transdermal iontophorethic drug delivery system.

    Science.gov (United States)

    Filipovic, Nenad; Saveljic, Igor; Rac, Vladislav; Graells, Beatriz Olalde; Bijelic, Goran

    2017-11-30

    The concept of iontophoresis is often applied to increase the transdermal transport of drugs and other bioactive agents into the skin or other tissues. It is a non-invasive drug delivery method which involves electromigration and electroosmosis in addition to diffusion and is shown to be a viable alternative to conventional administration routs such as oral, hypodermic and intravenous injection. In this study we investigated, experimentally and numerically, in vitro drug delivery of dexamethasone sodium phosphate to porcine skin. Different current densities, delivery durations and drug loads were investigated experimentally and introduced as boundary conditions for numerical simulations. Nernst-Planck equation was used for calculation of active substance flux through equivalent model of homogeneous hydrogel and skin layers. The obtained numerical results were in good agreement with experimental observations. A comprehensive in-silico platform, which includes appropriate numerical tools for fitting, could contribute to iontophoretic drug-delivery devices design and correct dosage and drug clearance profiles as well as to perform much faster in-silico experiments to better determine parameters and performance criteria of iontophoretic drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Filled carbon nanotubes in biomedical imaging and drug delivery.

    Science.gov (United States)

    Martincic, Markus; Tobias, Gerard

    2015-04-01

    Carbon nanotubes have been advocated as promising candidates in the biomedical field in the areas of diagnosis and therapy. In terms of drug delivery, the use of carbon nanotubes can overcome some limitations of 'free' drugs by improving the formulation of poorly water-soluble drugs, allowing targeted delivery and even enabling the co-delivery of two or more drugs for combination therapy. Two different approaches are currently being explored for the delivery of diagnostic and therapeutic agents by carbon nanotubes, namely attachment of the payload to the external sidewalls or encapsulation into the inner cavities. Although less explored, the latter confers additional stability to the chosen diagnostic or therapeutic agents, and leaves the backbone structure of the nanotubes available for its functionalization with dispersing and targeting moieties. Several drug delivery systems and diagnostic agents have been developed in the last years employing the inner tubular cavities of carbon nanotubes. The research discussed in this review focuses on the use of carbon nanotubes that contain in their interior drug molecules and diagnosis-related compounds. The approaches employed for the development of such nanoscale vehicles along with targeting and releasing strategies are discussed. The encapsulation of both biomedical contrast agents and drugs inside carbon nanotubes is further expanding the possibilities to allow an early diagnosis and treatment of diseases.

  7. Design of an Implantable Device for Ocular Drug Delivery

    Directory of Open Access Journals (Sweden)

    Jae-Hwan Lee

    2012-01-01

    Full Text Available Ocular diseases, such as, glaucoma, age-related macular degeneration (AMD, diabetic retinopathy, and retinitis pigmentosa require drug management in order to prevent blindness and affecting million of adults in USA and worldwide. There is an increasing need to develop devices for drug delivery to address ocular diseases. This study focuses on the design, simulation, and development of an implantable ocular drug delivery device consisting of micro-/nanochannels embedded between top and bottom covers with a drug reservoir made from polydimethylsiloxane (PDMS which is silicon-based organic and biodegradable polymer. Several simulations were carried out with six different micro-channel configurations in order to see the feasibility for ocular drug delivery applications. Based on the results obtained, channel design of osmotic I and osmotic II satisfied the diffusion rates required for ocular drug delivery. Finally, a prototype illustrating the three components of the drug delivery design is presented. In the future, the device will be tested for its functionality and diffusion characteristics.

  8. Combination of Polymer Technology and Carbon Nanotube Array for the Development of an Effective Drug Delivery System at Cellular Level

    Directory of Open Access Journals (Sweden)

    Riggio Cristina

    2009-01-01

    Full Text Available Abstract In this article, a carbon nanotube (CNT array-based system combined with a polymer thin film is proposed as an effective drug release device directly at cellular level. The polymeric film embedded in the CNT array is described and characterized in terms of release kinetics, while in vitro assays on PC12 cell line have been performed in order to assess the efficiency and functionality of the entrapped agent (neural growth factor, NGF. PC12 cell differentiation, following incubation on the CNT array embedding the alginate delivery film, demonstrated the effectiveness of the proposed solution. The achieved results indicate that polymeric technology could be efficiently embedded in CNT array acting as drug delivery system at cellular level. The implication of this study opens several perspectives in particular in the field of neurointerfaces, combining several functions into a single platform.

  9. Analyzing polymeric matrix for fabrication of a biodegradable microneedle array to enhance transdermal delivery.

    Science.gov (United States)

    Hwa, Kuo-Yuan; Chang, Vincent H S; Cheng, Yao-Yi; Wang, Yue-Da; Jan, Pey-Shynan; Subramani, Boopathi; Wu, Min-Ju; Wang, Bo-Kai

    2017-09-19

    Traditional drug delivery systems, using invasive, transdermal, and oral routes, are limited by various factors, such as the digestive system environment, skin protection, and sensory nerve stimulation. To improve the drug delivery system, we fabricated a polysaccharide-based, dissolvable microneedle-based array, which combines the advantages of both invasive and transdermal delivery systems, and promises to be an innovative solution for minimally invasive drug delivery. In this study, we designed a reusable aluminum mold that greatly improved the efficiency and convenience of microneedle fabrication. Physical characterization of the polysaccharides, individual or mixed at different ratios, was performed to identify a suitable molecule to fabricate the dissolvable microneedle. We used a vacuum deposition-based micro-molding method at low temperature to fabricate the model. Using a series of checkpoints from material into product, a systematic feedback mechanism was built into the "all-in-one" fabrication step, which helped to improve production yields. The physical properties of the fabricated microneedle were assessed. The cytotoxicity analysis and animal testing of the microneedle demonstrated the safety and compatibility of the microneedle, and the successful penetration and effective release of a model protein.

  10. Analysis of nifedipine content in transdermal drug delivery system using non-destructive visible spectrophotometry technique

    International Nuclear Information System (INIS)

    Normaizira Hamidi; Normaizira Hamidi; Normaizira Hamidi; Mohd Nasir Taib; Mohd Nasir Taib; Wui, Wong Tin; Wui, Wong Tin

    2008-01-01

    The applicability of visible spectrophotometry technique as a tool to determine the drug content of polymeric film for use as a transdermal drug delivery system was investigated. Hydroxypropylmethycellulose (HPMC) was selected as the matrix polymer and nifedipine as the model drug. Blank and nifedipine-loaded HPMC films were prepared using the solvent evaporation method. The absorbance spectra of these films under the visible wavelengths between 400 and 800 nm were assessed and compared against the drug content values obtained by means of the conventional destructive UV- spectrophotometry technique. The latter required the use of a solvent system which contained methanol, a harmful organic component in pharmaceutical applications. The results indicated that the absorbance values, attributed to nifedipine, at the wavelengths of 545, 585, 638 and 755nm were significantly correlated to the drug content values obtained using the chemical assay method (Pearson correlation value: r = 0.990 and p < 0.01). The visible spectrophotometry technique is potentially suitable for use to determine the nifedipine content of films owing to its nature of characterization of transdermal drug delivery system which does not require sample destruction during the process of measurement. The samples are recoverable from test and analysis of the entire batch of samples is possible without the need of solvents and chemical reagents. (author)

  11. 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.

  12. Liposome-based drug delivery in breast cancer treatment

    International Nuclear Information System (INIS)

    Park, John W

    2002-01-01

    Drug delivery systems can in principle provide enhanced efficacy and/or reduced toxicity for anticancer agents. Long circulating macromolecular carriers such as liposomes can exploit the 'enhanced permeability and retention' effect for preferential extravasation from tumor vessels. Liposomal anthracyclines have achieved highly efficient drug encapsulation, resulting in significant anticancer activity with reduced cardiotoxicity, and include versions with greatly prolonged circulation such as liposomal daunorubicin and pegylated liposomal doxorubicin. Pegylated liposomal doxorubucin has shown substantial efficacy in breast cancer treatment both as monotherapy and in combination with other chemotherapeutics. Additional liposome constructs are being developed for the delivery of other drugs. The next generation of delivery systems will include true molecular targeting; immunoliposomes and other ligand-directed constructs represent an integration of biological components capable of tumor recognition with delivery technologies

  13. Micro fabrication of biodegradable polymer drug delivery devices

    DEFF Research Database (Denmark)

    Nagstrup, Johan

    The pharmaceutical industry is presently facing several obstacles in developing oral drug delivery systems. This is primarily due to the nature of the discovered drug candidates. The discovered drugs often have poor solubility and low permeability across the gastro intestinal epithelium. Furtherm......The pharmaceutical industry is presently facing several obstacles in developing oral drug delivery systems. This is primarily due to the nature of the discovered drug candidates. The discovered drugs often have poor solubility and low permeability across the gastro intestinal epithelium...... permeability and degradation. These systems are for the majority based on traditional materials used in micro technology, such as SU-8, silicon, poly(methyl methacrylate). The next step in developing these new drug delivery systems is to replace classical micro fabrication materials with biodegradable polymers....... In order to successfully do this, methods for fabricating micro structures in biodegradable polymers need to be developed. The goal of this project has been to develop methods for micro fabrication in biodegradable polymers and to use these methods to produce micro systems for oral drug delivery. This has...

  14. Vaginal drug delivery systems: A Review of Current Status | Dobaria ...

    African Journals Online (AJOL)

    Among the various routes of drug delivery, the vaginal route offers many advantages due to its large permeation area, rich vascularization, avoidance of first pass metabolism and relatively low enzymatic activity. Several studies have shown that the vaginal cavity is an effective route for drug administration intended mainly ...

  15. Facilitating Intracellular Drug Delivery by Ultrasound-Activated Microbubbles

    NARCIS (Netherlands)

    Lammertink, BHA

    2017-01-01

    The goal of this thesis was to investigate the combination of ultrasound and microbubbles (USMB) for intracellular delivery of (model) drugs in vitro. We have focused on clinically approved drugs, i.e. cisplatin, and microbubbles, i.e. SonoVue™, to facilitate clinical translation. In addition, model

  16. Aptamer-Gated Nanoparticles for Smart Drug Delivery

    Directory of Open Access Journals (Sweden)

    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.

  17. Dry powder inhalers for pulmonary drug delivery

    NARCIS (Netherlands)

    Frijlink, H.W.; De Boer, A.H.

    2004-01-01

    The pulmonary route is an interesting route for drug administration, both for effective local therapy (asthma, chronic obstructive pulmonary disease or cystic fibrosis) and for the systemic administration of drugs (e.g., peptides and proteins). Well-designed dry powder inhalers are highly efficient

  18. Biopharmaceutical aspects of oral drug delivery

    NARCIS (Netherlands)

    Faassen, Werenfriedus Adrianus

    2004-01-01

    Most drugs display their therapeutic activity on specific places in the human body and should reach the systemic circulation in order to be transported towards the site of action. Irrespective of the route of administration the same sequence of steps are of relevance for the exposure to a drug:

  19. Solid lipid nanoparticles for parenteral drug delivery

    NARCIS (Netherlands)

    Wissing, S.A.; Kayser, Oliver; Muller, R.H.

    2004-01-01

    This review describes the use of nanoparticles based on solid lipids for the parenteral application of drugs. Firstly, different types of nanoparticles based on solid lipids such as "solid lipid nanoparticles" (SLN), "nanostructured lipid carriers" (NLC) and "lipid drug conjugate" (LDC)

  20. Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed-Dose Combination of Cardiovascular Drugs.

    Science.gov (United States)

    Quinn, Helen L; Bonham, Louise; Hughes, Carmel M; Donnelly, Ryan F

    2015-10-01

    Microneedles (MNs) are a minimally invasive drug delivery platform, designed to enhance transdermal drug delivery by breaching the stratum corneum. For the first time, this study describes the simultaneous delivery of a combination of three drugs using a dissolving polymeric MN system. In the present study, aspirin, lisinopril dihydrate, and atorvastatin calcium trihydrate were used as exemplar cardiovascular drugs and formulated into MN arrays using two biocompatible polymers, poly(vinylpyrrollidone) and poly(methylvinylether/maleic acid). Following fabrication, dissolution, mechanical testing, and determination of drug recovery from the MN arrays, in vitro drug delivery studies were undertaken, followed by HPLC analysis. All three drugs were successfully delivered in vitro across neonatal porcine skin, with similar permeation profiles achieved from both polymer formulations. An average of 126.3 ± 18.1 μg of atorvastatin calcium trihydrate was delivered, notably lower than the 687.9 ± 101.3 μg of lisinopril and 3924 ± 1011 μg of aspirin, because of the hydrophobic nature of the atorvastatin molecule and hence poor dissolution from the array. Polymer deposition into the skin may be an issue with repeat application of such a MN array, hence future work will consider more appropriate MN systems for continuous use, alongside tailoring delivery to less hydrophilic compounds. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  1. Microemulsion utility in pharmaceuticals: Implications for multi-drug delivery.

    Science.gov (United States)

    Callender, Shannon P; Mathews, Jessica A; Kobernyk, Katherine; Wettig, Shawn D

    2017-06-30

    Emulsion technology has been utilized extensively in the pharmaceutical industry. This article presents a comprehensive review of the literature on an important subcategory of emulsions, microemulsions. Microemulsions are optically transparent, thermodynamically stable colloidal systems, 10-100nm diameter, that form spontaneously upon mixing of oil, water and emulsifier. This review is the first to address advantages and disadvantages, as well as considerations and challenges in multi-drug delivery. For the period 1 January 2011-30 April 2016, 431 publications related to microemulsion drug delivery were identified and screened according to microemulsion, drug classification, and surfactant types. Results indicate the use of microemulsions predominantly in lipophilic drug delivery (79.4%) via oil-in-water microemulsions and non-ionic surfactants (90%) for oral or topical administration. Cancer is the disease state most targeted followed by inflammatory diseases, microbial infections and cardiovascular disease. Key generalizations from this analysis include: 1) microemulsion formulation is largely based on trial-and-error despite over 1200 publications related to microemulsion drug delivery since their discovery in 1943; 2) characterization using methods including interfacial tension, droplet size, electrical conductivity, turbidity and viscosity may provide additional information for greater predictability; 3) microemulsion drug delivery publications arise primarily from China (27%) and India (21%) suggesting additional research opportunities elsewhere. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. 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.

  3. Laser assisted drug delivery: a review of an evolving technology.

    Science.gov (United States)

    Sklar, Lindsay R; Burnett, Christopher T; Waibel, Jill S; Moy, Ronald L; Ozog, David M

    2014-04-01

    Topically applied drugs have a relatively low cutaneous bioavailability. This article reviews the existing applications of laser assisted drug delivery, a means by which the permeation of topically applied agents can be enhanced into the skin. The existing literature suggests that lasers are a safe and effective means of enhancing the delivery of topically applied agents through the skin. The types of lasers most commonly studied in regards to drug delivery are the carbon dioxide (CO2 ) and erbium:yttrium-aluminum-garnet (Er:YAG) lasers. Both conventional ablative and fractional ablative modalities have been utilized and are summarized herein. The majority of the existing studies on laser assisted drug delivery have been performed on animal models and additional human studies are needed. Laser assisted drug delivery is an evolving technology with potentially broad clinical applications. Multiple studies demonstrate that laser pretreatment of the skin can increase the permeability and depth of penetration of topically applied drug molecules for both local cutaneous and systemic applications. © 2014 Wiley Periodicals, Inc.

  4. Chemistry, manufacturing and controls in passive transdermal drug delivery systems.

    Science.gov (United States)

    Goswami, Tarun; Audett, Jay

    2015-01-01

    Transdermal drug delivery systems (TDDS) are used for the delivery of the drugs through the skin into the systemic circulation by applying them to the intact skin. The development of TDDS is a complex and multidisciplinary affair which involves identification of suitable drug, excipients and various other components. There have been numerous problems reported with respect to TDDS quality and performance. These problems can be reduced by appropriately addressing chemistry, manufacturing and controls requirements, which would thereby result in development of robust TDDS product and processes. This article provides recommendations on the chemistry, manufacturing and controls focusing on the unique technical aspects of TDDS.

  5. Carbon nanotubes buckypapers for potential transdermal drug delivery

    International Nuclear Information System (INIS)

    Schwengber, Alex; Prado, Héctor J.; Zilli, Darío A.; Bonelli, Pablo R.

    2015-01-01

    Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT–drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect. - Highlights: • Drug loaded buckypapers from carbon nanotubes were prepared and characterized. • Their potentialities for transdermal drug delivery applications were evaluated. • Characteristics of carbon nanotubes and the structure of the drug affected release • A higher carbon nanotube:drug mass ratio decelerated release • Up to one week controlled release profiles were obtained for the drug flurbiprofen

  6. Carbon nanotubes buckypapers for potential transdermal drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Schwengber, Alex [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Prado, Héctor J. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Cátedra de Tecnología Farmacéutica II, Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, C1033AAJ Buenos Aires (Argentina); Zilli, Darío A. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Bonelli, Pablo R. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, C1033AAJ Buenos Aires (Argentina); and others

    2015-12-01

    Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT–drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect. - Highlights: • Drug loaded buckypapers from carbon nanotubes were prepared and characterized. • Their potentialities for transdermal drug delivery applications were evaluated. • Characteristics of carbon nanotubes and the structure of the drug affected release • A higher carbon nanotube:drug mass ratio decelerated release • Up to one week controlled release profiles were obtained for the drug flurbiprofen.

  7. Fabrication and loading of microcontainers for oral drug delivery

    DEFF Research Database (Denmark)

    Petersen, Ritika Singh

    is an important loop diuretic drug with low solubility and permeability is used as a model drug and embedded in a PCL matrix. The crystallinity of the drug is tailored by the process parameters of spin coating. Release profiles ranging from rapid burst release to sustained zero-order release are obtained......Oral drug delivery is considered as the most patient compliant delivery route. However, it faces many obstacles, especially due to the ever-increasing number of drugs that are poorly soluble and barely absorbed in the gastro-intestinal tract. Moreover, drugs can degrade in the harsh acidic...... in this project. This process utilizes a stamp in connection with the ability to apply heat and pressure to transfer the stamp pattern to a film. Processes have been optimized for fabrication of nickel stamps with two layered, high aspect ratio microstructures. Bosch deep reactive ion etching of Silicon producing...

  8. Protein cages and synthetic polymers: a fruitful symbiosis for drug delivery applications, bionanotechnology and materials science.

    Science.gov (United States)

    Rother, Martin; Nussbaumer, Martin G; Renggli, Kasper; Bruns, Nico

    2016-11-07

    Protein cages are hollow protein nanoparticles, such as viral capsids, virus-like particles, ferritin, heat-shock proteins and chaperonins. They have well-defined capsule-like structures with a monodisperse size. Their protein subunits can be modified by genetic engineering at predetermined positions, allowing for example site-selective introduction of attachment points for functional groups, catalysts or targeting ligands on their outer surface, in their interior and between subunits. Therefore, protein cages have been extensively explored as functional entities in bionanotechnology, as drug-delivery or gene-delivery vehicles, as nanoreactors or as templates for the synthesis of organic and inorganic nanomaterials. The scope of functionalities and applications of protein cages can be significantly broadened if they are combined with synthetic polymers on their surface or within their interior. For example, PEGylation reduces the immunogenicity of protein cage-based delivery systems and active targeting ligands can be attached via polymer chains to favour their accumulation in diseased tissue. Polymers within protein cages offer the possibility of increasing the loading density of drug molecules, nucleic acids, magnetic resonance imaging contrast agents or catalysts. Moreover, the interaction of protein cages and polymers can be used to modulate the size and shape of some viral capsids to generate structures that do not occur with native viruses. Another possibility is to use the interior of polymer cages as a confined reaction space for polymerization reactions such as atom transfer radical polymerization or rhodium-catalysed polymerization of phenylacetylene. The protein nanoreactors facilitate a higher degree of control over polymer synthesis. This review will summarize the hybrid structures that have been synthesized by polymerizing from protein cage-bound initiators, by conjugating polymers to protein cages, by embedding protein cages into bulk polymeric

  9. Albumin-based drug delivery: harnessing nature to cure disease.

    Science.gov (United States)

    Larsen, Maja Thim; Kuhlmann, Matthias; Hvam, Michael Lykke; Howard, Kenneth A

    2016-01-01

    The effectiveness of a drug is dependent on accumulation at the site of action at therapeutic levels, however, challenges such as rapid renal clearance, degradation or non-specific accumulation requires drug delivery enabling technologies. Albumin is a natural transport protein with multiple ligand binding sites, cellular receptor engagement, and a long circulatory half-life due to interaction with the recycling neonatal Fc receptor. Exploitation of these properties promotes albumin as an attractive candidate for half-life extension and targeted intracellular delivery of drugs attached by covalent conjugation, genetic fusions, association or ligand-mediated association. This review will give an overview of albumin-based products with focus on the natural biological properties and molecular interactions that can be harnessed for the design of a next-generation drug delivery platform.

  10. 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.

  11. Porous Polymer Drug-Eluting Coating Prepared by Radiation Induced Polymerization

    International Nuclear Information System (INIS)

    Veres, M.; Tóth, S.; Koós, M.; Beiler, B.

    2009-01-01

    Drug-eluting stents have several advantages over bare metal implants. They eliminate restenosis, the main drawback of bare metal stents. In addition the locally delivered drug is more effective and causes less side-effects. However in some cases dangerous stent thrombosis, inflammatory and allergy reactions were observed after their implantation, which first of all related to the drug-eluting coating. This project is aimed to develop a novel biocompatible nanoporous polymer layer by radiation induced polymerization that is capable of holding and eluting drugs and promotes endothelization after the release of the drug. (author)

  12. Porous Polymer Drug-Eluting Coating Prepared by Radiation Induced Polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Veres, M.; Tóth, S.; Koós, M. [Research Institute for Solid State Physics and Optics, Budapest (Hungary); Beiler, B. [Institute of Isotopes, HAS, Budapest (Hungary)

    2009-07-01

    Drug-eluting stents have several advantages over bare metal implants. They eliminate restenosis, the main drawback of bare metal stents. In addition the locally delivered drug is more effective and causes less side-effects. However in some cases dangerous stent thrombosis, inflammatory and allergy reactions were observed after their implantation, which first of all related to the drug-eluting coating. This project is aimed to develop a novel biocompatible nanoporous polymer layer by radiation induced polymerization that is capable of holding and eluting drugs and promotes endothelization after the release of the drug. (author)