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Sample records for biodegradable drug carriers

  1. Photothermal and biodegradable polyaniline/porous silicon hybrid nanocomposites as drug carriers for combined chemo-photothermal therapy of cancer.

    Science.gov (United States)

    Xia, Bing; Wang, Bin; Shi, Jisen; Zhang, Yu; Zhang, Qi; Chen, Zhenyu; Li, Jiachen

    2017-03-15

    To develop photothermal and biodegradable nanocarriers for combined chemo-photothermal therapy of cancer, polyaniline/porous silicon hybrid nanocomposites had been successfully fabricated via surface initiated polymerization of aniline onto porous silicon nanoparticles in our experiments. As-prepared polyaniline/porous silicon nanocomposites could be well dispersed in aqueous solution without any extra hydrophilic surface coatings, and showed a robust photothermal effect under near-infrared (NIR) laser irradiation. Especially, after an intravenous injection into mice, these biodegradable porous silicon-based nanocomposites as non-toxic agents could be completely cleared in body. Moreover, these polyaniline/porous silicon nanocomposites as drug carriers also exhibited an efficient loading and dual pH/NIR light-triggered release of doxorubicin hydrochloride (DOX, a model anticancer drug). Most importantly, assisted with NIR laser irradiation, polyaniline/PSiNPs nanocomposites with loading DOX showed a remarkable synergistic anticancer effect combining chemotherapy with photothermal therapy, whether in vitro or in vivo. Therefore, based on biodegradable PSiNPs-based nanocomposites, this combination approach of chemo-photothermal therapy would have enormous potential on clinical cancer treatments in the future. Considering the non-biodegradable nature and potential long-term toxicity concerns of photothermal nanoagents, it is of great interest and importance to develop biodegradable and photothermal nanoparticles with an excellent biocompatibility for their future clinical applications. In our experiments, we fabricated porous silicon-based hybrid nanocomposites via surface initiated polymerization of aniline, which showed an excellent photothermal effect, aqueous dispersibility, biodegradability and biocompatibility. Furthermore, after an efficient loading of DOX molecules, polyaniline/porous silicon nanocomposites exhibited the remarkable synergistic anticancer

  2. Biodegradable multiblock polymers based on N-(2-hydroxypropyl)methacrylamide designed as drug carriers for tumor-targeted delivery

    Czech Academy of Sciences Publication Activity Database

    Mužíková, Gabriela; Pola, Robert; Laga, Richard; Pechar, Michal

    2016-01-01

    Roč. 217, č. 15 (2016), s. 1690-1703 ISSN 1022-1352 R&D Projects: GA ČR(CZ) GA14-12742S; GA ČR(CZ) GA16-17207S; GA MŠk(CZ) LO1507; GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61389013 Keywords : biodegradable polymers * click chemistry * drug delivery systems Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.500, year: 2016

  3. Novel Biodegradable Polyesters. Synthesis and Application as Drug Carriers for the Preparation of Raloxifene HCl Loaded Nanoparticles

    Directory of Open Access Journals (Sweden)

    Evangelos Karavas

    2009-07-01

    Full Text Available Raloxifene HCl is a drug with poor bioavailability and poor water solubility. Furthermore nο pharmaceutically acceptable organic solvent has been reported before to dilute the drug. It was observed that Raloxifene HCl can be diluted in a solvent mixture of acetone/water or ethanol/water. The aim of this study was to use biodegradable polymers in order to prepare Raloxifene HCl nanoparticles. For this purpose a series of novel biodegradable poly(ethylene succinate-co-propylene adipate P(ESu-co-PAd polyesters were synthesized following the polycondensation method and further, poly(ethylene succinate (PESu and poly(propylene adipate (PPAd were used. The prepared polyesters were characterized by intrinsic viscosity measurements, end group analysis, enzymatic hydrolysis, Nuclear Magnetic Resonance Spectroscopy (1Η-NMR and 13C-NMR and Wide-angle X-ray Diffractometry (WAXD. The drug nanoparticles have been prepared by a variation of the co-precipitation method and were studied by Wide-angle X-ray Diffractometry (WAXD, FTIR spectrometry, light scattering size distribution, Scanning Electron Microscopy (SEM and release behavior measurements. The interactions between the polymers and the drug seem to be limited, so the drug occurs in crystalline form in all nanoparticles. The size of the nanoparticles seems to be in the range of 150-350 nm, depending on the polymer that was used. The drug release depends on the melting point and degree of crystallinity of the polyesters used. An initial high release rate was recorded followed by very slow rates of controlled release.

  4. Synthesis, characterization, and property of biodegradable PEG-PCL-PLA terpolymers with miktoarm star and triblock architectures as drug carriers.

    Science.gov (United States)

    Zhang, Yixin; Luo, Song; Liang, Yan; Zhang, Hai; Peng, Xinyu; He, Bin; Li, Sai

    2018-03-01

    A series of amphiphilic terpolymers with miktoarm star and triblock architectures of poly(ethylene glycol) (PEG), poly(ε-caprolactone) (PCL) and poly(l-lactide acid) (PLLA) or poly(DL-lactide acid) (PDLLA) terpolymers were synthesized as carriers for drug delivery. The architecture, molecular weight and crystallization behavior of the terpolymers were characterized. Anticancer drug doxorubicin was encapsulated in the micelles to investigate their drug loading properties. The miktoarm star terpolymers exhibited stronger crystallization capability, smaller size and better stability than that of triblock polymeric micelle, owing to the lower CMC values of miktoarm star polymeric micelle. Furthermore, the drug-loaded miktoarm star polymeric micelles showed the cumulative DOX release account of the micelles with PDLLA blocks was 65.3% while the release account of the corresponding micelles containing PLLA blocks was 45.2%. The IC 50 values of drug-loaded miktoarm star polymeric micelle were lower than triblock polymeric micelle. Meanwhile, Confocal laser scanning microscopy (CLSM) and Flow Cytometry results demonstrated that the miktoarm star micelles were more favorable for cellular internalization. The miktoarm star micelles with PDLLA blocks were promising carriers for anticancer drug delivery.

  5. 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)

  6. Cyclodextrins in drug carrier systems.

    Science.gov (United States)

    Uekama, K; Otagiri, M

    1987-01-01

    One of the important characteristics of cyclodextrins is the formation of an inclusion complex with a variety of drug molecules in solution and in the solid state. As a consequence of intensive basic research, exhaustive toxic studies, and realization of industrial production during the past decade, there seem to be no more barriers for the practical application of natural cyclodextrins in the biomedical field. Recently, a number of cyclodextrin derivatives and cyclodextrin polymers have been prepared to obtain better inclusion abilities than parent cyclodextrins. The natural cyclodextrins and their synthetic derivatives have been successfully utilized to improve various drug properties, such as solubility, dissolution and release rates, stability, or bioavailability. In addition, the enhancement of drug activity, selective transfer, or the reduction of side effects has been achieved by means of inclusion complexation. The drug-cyclodextrin complex is generally formed outside of the body and, after administration, it dissociates, releasing the drug into the organism in a fast and nearly uniform manner. In the biomedical application of cyclodextrins, therefore, particular attention should be directed to the magnitude of the stability constant of the inclusion complex. In the case of parenteral application, a rather limited amount of work has been done because the cyclodextrins in the drug carrier systems have to be more effectively designed to compete with various biological components in the circulatory system. However, the works published thus far apparently indicate that the inclusion phenomena of cyclodextrin analogs may allow the rational design of drug formulation and that the combination of molecular encapsulation with other carrier systems will become a very effective and valuable method for the development of a new drug delivery system in the near future.

  7. 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.

  8. POLYURETHANE COMPOSITES AS DRUG CARRIERS:: RELEASE PATTERNS

    Directory of Open Access Journals (Sweden)

    M. V. Grigoreva

    2013-10-01

    Full Text Available Biodegradable polyurethanes attract interest of those developing composite materials for biomedical applications. One of their features is their ability to serve as carriers, or matrixes, for medicines and other bioactive compounds to produce a therapeutic effect in body through targeted and/or prolonged delivery of these compounds in the process of their controlled release from matrix. The review presents polyurethane composites as matrices for a number of drugs. The relation between structure of the composites and their degradability both in vitro and in vivo and the dependence of drug release kinetics on physicochemical properties of polyurethane matrix are highlighted. The release of drugs (cefazolin, naltrexone and piroxicam from the composites based on cross-linked polyurethanes (synthesized from laprols, Mw between 1,500 and 2,000 Da and toluylene diisocyanate demonstrated more or less the same pattern (about 10 days in vitro and three to five days in vivo. In contrast, the composites with dioxydine based on a linear polyurethanes (synthesized from oligotetramethilene glycol, Mw 1,000 Da, diphenylmethane-4,4’-diisocyanate and 1,4-butanediol retained their antimicrobial activity at least 30 days. They also showed a significantly higher breaking strength as compared to that of the composites based on cross-linked polyurethanes.

  9. 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.

  10. Biodegradable hollow fibres for the controlled release of drugs

    NARCIS (Netherlands)

    Schakenraad, J.M.; Oosterbaan, J.A.; Nieuwenhuis, P.; Molenaar, I.; Olijslager, J.; Potman, W.; Eenink, M.J.D.; Feijen, Jan

    1988-01-01

    Biodegradable hollow fibres of poly-l-lactic acid (PLLA) filled with a suspension of the contraceptive hormone levonorgestrel in castor oil were implanted subcutaneously in rats to study the rate of drug release, rate of biodegradation and tissue reaction caused by the implant. The in vivo drug

  11. Hybrid nanostructured drug carrier with tunable and controlled drug release

    International Nuclear Information System (INIS)

    Depan, D.; Misra, R.D.K.

    2012-01-01

    We describe here a transformative approach to synthesize a hybrid nanostructured drug carrier that exhibits the characteristics of controlled drug release. The synthesis of the nanohybrid architecture involved two steps. The first step involved direct crystallization of biocompatible copolymer along the long axis of the carbon nanotubes (CNTs), followed by the second step of attachment of drug molecule to the polymer via hydrogen bonding. The extraordinary inorganic–organic hybrid architecture exhibited high drug loading ability and is physically stable even under extreme conditions of acidic media and ultrasonic irradiation. The temperature and pH sensitive characteristics of the hybrid drug carrier and high drug loading ability merit its consideration as a promising carrier and utilization of the fundamental aspects used for synthesis of other promising drug carriers. The higher drug release response during the application of ultrasonic frequency is ascribed to a cavitation-type process in which the acoustic bubbles nucleate and collapse releasing the drug. Furthermore, the study underscores the potential of uniquely combining CNTs and biopolymers for drug delivery. - Graphical abstract: Block-copolymer crystallized on carbon nanotubes (CNTs). Nanohybrid drug carrier synthesized by attaching doxorubicin (DOX) to polymer crystallized CNTs. Crystallized polymer on CNTs provide mechanical stability. Triggered release of DOX. Highlights: ► The novel synthesis of a hybrid nanostructured drug carrier is described. ► The drug carrier exhibits high drug loading ability and is physically stable. ► The high drug release is ascribed to a cavitation-type process.

  12. Chitosan and its derivatives as promising drug delivery carriers

    CERN Document Server

    Prabaharan, M

    2012-01-01

    Chitosan, a natural based polymer obtained by alkaline deacetylation of chitin, is non-toxic, biocompatible, and biodegradable. These properties make chitosan a good candidate for the development of conventional and novel drug delivery systems. Recently, there has been a growing interest in the chemical modification of chitosan in order to improve its solubility and widen its applications. Chemical modification of chitosan is useful for the association of bioactive molecules to the polymer and controlling the drug release profile. Chemical modification will introduce desired properties and enlarge the field of the potential applications of chitosan with the choice of various types of side chains. In this monograph, recent studies on the various types of chitosan microspheres are discussed from the viewpoint of drug delivery applications. Moreover, different types of chitosan derivatives developed as controlled drug delivery carriers and their preparation methods are discussed in detail. The modifications disc...

  13. Current knowledge on biodegradable microspheres in drug delivery.

    Science.gov (United States)

    Prajapati, Vipul D; Jani, Girish K; Kapadia, Jinita R

    2015-08-01

    Biodegradable microspheres have gained popularity for delivering a wide variety of molecules via various routes. These types of products have been prepared using various natural and synthetic biodegradable polymers through suitable techniques for desired delivery of various challenging molecules. Selection of biodegradable polymers and technique play a key role in desired drug delivery. This review describes an overview of the fundamental knowledge and status of biodegradable microspheres in effective delivery of various molecules via desired routes with consideration of outlines of various compendial and non-compendial biodegradable polymers, formulation techniques and release mechanism of microspheres, patents and commercial biodegradable microspheres. There are various advantages of using biodegradable polymers including promise of development with different types of molecules. Biocompatibility, low dosage and reduced side effects are some reasons why usage biodegradable microspheres have gained in popularity. Selection of biodegradable polymers and formulation techniques to create microspheres is the biggest challenge in research. In the near future, biodegradable microspheres will become the eco-friendly product for drug delivery of various genes, hormones, proteins and peptides at specific site of body for desired periods of time.

  14. Nanostructured Lipid Carriers: A potential drug carrier for cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Selvamuthukumar Subramanian

    2012-11-01

    Full Text Available Abstract Nanotechnology having developed exponentially, the aim has been on therapeutic undertaking, particularly for cancerous disease chemotherapy. Nanostructured lipid carriers have attracted expanding scientific and commercial vigilance in the last couple of years as alternate carriers for the pharmaceutical consignment, particularly anticancer pharmaceuticals. Shortcomings often came across with anticancer mixtures, such as poor solubility, normal tissue toxicity, poor specificity and steadiness, as well as the high incidence rate of pharmaceutical resistance and the rapid degradation, need of large-scale output procedures, a fast release of the pharmaceutical from its carrier scheme, steadiness troubles, the residues of the organic solvents utilized in the output method and the toxicity from the polymer with esteem to the carrier scheme are anticipated to be overcome through use of the Nanostructured Lipid Carrier. In this review the benefits, types, drug release modulations, steadiness and output techniques of NLCs are discussed. In supplement, the function of NLC in cancer chemotherapy is presented and hotspots in research are emphasized. It is foreseen that, in the beside future, nanostructured lipid carriers will be further advanced to consign cytotoxic anticancer compounds in a more efficient, exact and protected manner.

  15. 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.

  16. Polyamidoamines as Drug Carriers: Synthesis of Polymers ...

    African Journals Online (AJOL)

    NJD

    The versatile polymerization of bisacrylamides with mono- and difunctional amines, first investigated and greatly expanded in. Ferruti's laboratory,1–3 is utilized in the present project for the synthesis of macromolecular drug carriers. Specifically, we report on the preparation of linear polyamidoamines possessing primary ...

  17. Biocompatibility of new drug-eluting biodegradable urethral stent materials.

    Science.gov (United States)

    Kotsar, Andres; Nieminen, Riina; Isotalo, Taina; Mikkonen, Joonas; Uurto, Ilkka; Kellomäki, Minna; Talja, Martti; Moilanen, Eeva; Tammela, Teuvo L J

    2010-01-01

    To investigate the effects of biodegradable stent material (poly-96L/4D-lactic acid [PLA]) on the production of cytokines and other inflammatory mediators in vitro and the biocompatibility of new drug-eluting biodegradable urethral stent materials in vivo. Indomethacin, dexamethasone, and simvastatin were used in the materials. The effects of the biodegradable stent material on cytokines and other inflammatory mediators were measured using the Human Cytokine Antibody Array and enzyme-linked immunosorbent assay in THP-1 cells, with bacterial lipopolysaccharide as a positive control. To assess the biocompatibility of the stent materials, we used muscle implantation. Biodegradable stent materials without drug-eluting properties and silicone and latex were used as controls. The measurements were done at 3 weeks and 3 months. The PLA stent material induced production of inflammatory mediators, especially interleukin-8, tumor necrosis factor-alpha, and transforming growth factor-beta, in vitro. The increase in the production of these mediators with the PLA stent material was smaller than in the cells treated with lipopolysaccharide. In vivo, the effects of the biodegradable materials did not differ at 3 weeks, although, at 3 months, dexamethasone had induced more tissue reactions than had the other materials. At 3 months, fibrosis and chronic inflammatory changes were decreased in the biodegradable material groups compared with the positive control. PLA stent material increased the production of cytokines and other inflammatory mediators less than did positive controls in vitro. The in vivo biocompatibility of the drug-eluting biodegradable materials was better than that of the positive controls. Drug-eluting biodegradable urethral stents could potentially offer a new treatment modality in the future. 2010 Elsevier Inc. All rights reserved.

  18. Aptamers as Both Drugs and Drug-Carriers

    Directory of Open Access Journals (Sweden)

    Md. Ashrafuzzaman

    2014-01-01

    Full Text Available Aptamers are short nucleic acid oligos. They may serve as both drugs and drug-carriers. Their use as diagnostic tools is also evident. They can be generated using various experimental, theoretical, and computational techniques. The systematic evolution of ligands by exponential enrichment which uses iterative screening of nucleic acid libraries is a popular experimental technique. Theory inspired methodology entropy-based seed-and-grow strategy that designs aptamer templates to bind specifically to targets is another one. Aptamers are predicted to be highly useful in producing general drugs and theranostic drugs occasionally for certain diseases like cancer, Alzheimer’s disease, and so on. They bind to various targets like lipids, nucleic acids, proteins, small organic compounds, and even entire organisms. Aptamers may also serve as drug-carriers or nanoparticles helping drugs to get released in specific target regions. Due to better target specific physical binding properties aptamers cause less off-target toxicity effects. Therefore, search for aptamer based drugs, drug-carriers, and even diagnostic tools is expanding fast. The biophysical properties in relation to the target specific binding phenomena of aptamers, energetics behind the aptamer transport of drugs, and the consequent biological implications will be discussed. This review will open up avenues leading to novel drug discovery and drug delivery.

  19. Microneedles array with biodegradable tips for transdermal drug delivery

    Science.gov (United States)

    Iliescu, Ciprian; Chen, Bangtao; Wei, Jiashen; Tay, Francis E. H.

    2008-12-01

    The paper presented an enhancement solution for transdermal drug delivery using microneedles array with biodegradable tips. The microneedles array was fabricated by using deep reactive ion etching (DRIE) and the biodegradable tips were made to be porous by electrochemical etching process. The porous silicon microneedle tips can greatly enhance the transdermal drug delivery in a minimum invasion, painless, and convenient manner, at the same time; they are breakable and biodegradable. Basically, the main problem of the silicon microneedles consists of broken microneedles tips during the insertion. The solution proposed is to fabricate the microneedle tip from a biodegradable material - porous silicon. The silicon microneedles are fabricated using DRIE notching effect of reflected charges on mask. The process overcomes the difficulty in the undercut control of the tips during the classical isotropic silicon etching process. When the silicon tips were formed, the porous tips were then generated using a classical electrochemical anodization process in MeCN/HF/H2O solution. The paper presents the experimental results of in vitro release of calcein and BSA with animal skins using a microneedle array with biodegradable tips. Compared to the transdermal drug delivery without any enhancer, the microneedle array had presented significant enhancement of drug release.

  20. Nanocomposites of Polyacrylic Acid Nanogels and Biodegradable Polyhydroxybutyrate for Bone Regeneration and Drug Delivery

    Directory of Open Access Journals (Sweden)

    Mikael Larsson

    2014-01-01

    Full Text Available Biodegradable cell scaffolds and local drug delivery to stimulate cell response are currently receiving much scientific attention. Here we present a nanocomposite that combines biodegradation with controlled release of lithium, which is known to enhance bone growth. Nanogels of lithium neutralized polyacrylic acid were synthesized by microemulsion-templated polymerization and were incorporated into a biodegradable polyhydroxybutyrate (PHB matrix. Nanogel size was characterized using dynamic light scattering, and the nanocomposites were characterized with regard to structure using scanning electron microscopy, mechanical properties using tensile testing, permeability using tritiated water, and lithium release in PBS using a lithium specific electrode. The nanogels were well dispersed in the composites and the mechanical properties were good, with a decrease in elastic modulus being compensated by increased tolerance to strain in the wet state. Approximately half of the lithium was released over about three hours, with the remaining fraction being trapped in the PHB for subsequent slow release during biodegradation. The prepared nanocomposites seem promising for use as dual functional scaffolds for bone regeneration. Here lithium ions were chosen as model drug, but the nanogels could potentially act as carriers for larger and more complex drugs, possibly while still carrying lithium.

  1. Biocompatible medical implant materials with binding sites for a biodegradable drug-delivery system

    Directory of Open Access Journals (Sweden)

    Al-Dubai H

    2011-10-01

    Full Text Available Haifa Al-Dubai1, Gisela Pittner1, Fritz Pittner1, Franz Gabor21Max F Perutz Laboratories, Department of Biochemistry, University of Vienna, Vienna, Austria; 2Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Life Sciences, University of Vienna, Vienna, AustriaAbstract: Feasibility studies have been carried out for development of a biocompatible coating of medical implant materials allowing the binding of biodegradable drug-delivery systems in a way that their reloading might be possible. These novel coatings, able to bind biodegradable nanoparticles, may serve in the long run as drug carriers to mediate local pharmacological activity. After biodegradation of the nanoparticles, the binding sites could be reloaded with fresh drug-delivering particles. As a suitable receptor system for the nanoparticles, antibodies are anchored. The design of the receptor is of great importance as any bio- or chemorecognitive interaction with other components circulating in the blood has to be avoided. Furthermore, the binding between receptor and the particles has to be strong enough to keep them tightly bound during their lifetime, but on the other hand allow reloading after final degradation of the particles. The nanoparticles suggested as a drug-delivery system for medical implants can be loaded with different pharmaceuticals such as antibiotics, growth factors, or immunosuppressives. This concept may enable the changing of medication, even after implantation of the medical device, if afforded by patients’ needs.Keywords: antibody immobilization, biocompatible coating, chitosan nanoparticles, drug targeting, medical device

  2. Tissue biocompatibility of new biodegradable drug-eluting stent materials.

    Science.gov (United States)

    Uurto, Ilkka; Kotsar, Andres; Isotalo, Taina; Mikkonen, Joonas; Martikainen, Paula M; Kellomäki, Minna; Törmälä, Pertti; Tammela, Teuvo L J; Talja, Martti; Salenius, Juha-Pekka

    2007-08-01

    Drug-eluting stents are a recent innovation for endovascular and endourethral purposes. The aim of this study was to assess the biocompatibility of new biodegradable drug-eluting stent materials in vivo. Rods made of SR-PLDLA (self-reinforced poly-96L,4D: -lactic acid) covered with P(50L/50D)LA and rods made of 96L/4D SR-PLA and covered with P(50L/50D)LA including indomethacin 3.3 microg/mm(2)or dexamethasone 1.5 microg/mm(2), were inserted into the dorsal muscles of 20 rabbits serving as test animals. Rods made of silicone and organotin-positive polyvinylchloride were used as negative and positive controls. The animals were sacrificed after 1 week, 1 month, 2 months or 4 months. Histological changes attributable to the operative trauma were seen in all specimens at 1 week and 1 month. At 2 months both dexamethasone and indomethacin induced less fibrosis than the plain SR-PLDLA covered with P(50L/50D)LA without drug. At 4 months dexamethasone induced both chronic inflammatory changes and foreign body reaction, whereas the reactions in the indomethacin and drug-free plain SR-PLDLA groups were insignificant. The new biodegradable drug-eluting stent materials are highly biocompatible. Drug-eluting biodegradable stents may offer a promising new treatment modality for vascular and urethral diseases. However, further studies are needed to demonstrate their feasibility and efficacy.

  3. Payload drug vs. nanocarrier biodegradation by myeloperoxidase- and peroxynitrite-mediated oxidations: pharmacokinetic implications

    Science.gov (United States)

    Seo, Wanji; Kapralov, Alexandr A.; Shurin, Galina V.; Shurin, Michael R.; Kagan, Valerian E.; Star, Alexander

    2015-05-01

    With the advancement of nanocarriers for drug delivery into biomedical practice, assessments of drug susceptibility to oxidative degradation by enzymatic mechanisms of inflammatory cells become important. Here, we investigate oxidative degradation of a carbon nanotube-based drug carrier loaded with Doxorubicin. We employed myeloperoxidase-catalysed and peroxynitrite-mediated oxidative conditions to mimic the respiratory burst of neutrophils and macrophages, respectively. In addition, we revealed that the cytostatic and cytotoxic effects of free Doxorubicin, but not nanotube-carried drug, on melanoma and lung carcinoma cell lines were abolished in the presence of tumor-activated myeloid regulatory cells that create unique myeloperoxidase- and peroxynitrite-induced oxidative conditions. Both ex vivo and in vitro studies demonstrate that the nanocarrier protects the drug against oxidative biodegradation.With the advancement of nanocarriers for drug delivery into biomedical practice, assessments of drug susceptibility to oxidative degradation by enzymatic mechanisms of inflammatory cells become important. Here, we investigate oxidative degradation of a carbon nanotube-based drug carrier loaded with Doxorubicin. We employed myeloperoxidase-catalysed and peroxynitrite-mediated oxidative conditions to mimic the respiratory burst of neutrophils and macrophages, respectively. In addition, we revealed that the cytostatic and cytotoxic effects of free Doxorubicin, but not nanotube-carried drug, on melanoma and lung carcinoma cell lines were abolished in the presence of tumor-activated myeloid regulatory cells that create unique myeloperoxidase- and peroxynitrite-induced oxidative conditions. Both ex vivo and in vitro studies demonstrate that the nanocarrier protects the drug against oxidative biodegradation. Electronic supplementary information (ESI) available: Experimental details and data from characterization of materials synthesis and degradation studies. See DOI: 10

  4. Novel pH-sensitive biodegradable polymeric drug delivery systems based on ketal polymers.

    Science.gov (United States)

    Chen, Daquan; Wang, Hongbo

    2014-01-01

    This article reviews the recent developments on novel pH-sensitive ketal-based biodegradable polymeric drug delivery systems. Due to the degradation of ketal derivatives, neutral alcohols and ketones, ketal derivatives can be used to fabricate pH-degradable polymer with pH-degradable ketal linkages in new drug delivery systems by avoiding inflammatory problems. Due to the novelty of ketal polymers, there were few reports about ketal polymers. The review starts with a brief introduction to the pH-sensitive drug delivery system, followed by the structure, preparation and characterization techniques of ketal polymers. Thereafter, the promising applications in various diseases in relation to micro/nano drug carriers based on ketal polymers are summarized and discussed.

  5. Sensitive Drug Carrier for Sustained Release of Cefixime

    African Journals Online (AJOL)

    Abstract. Purpose: To formulate and evaluate pH-sensitive controlled release cefixime microspheres based on crosslinked chitosan and acryl ... serve as an effective biodegradable carrier for controlled release of cefixime. Keywords: Chitosan ..... DSC is a useful tool that could assist in determining if any changes have taken ...

  6. Micro fabrication of biodegradable polymer drug delivery devices

    DEFF Research Database (Denmark)

    Nagstrup, Johan

    . Furthermore, they are often degraded before they can be absorbed. The result is low bioavailability of the drugs. To overcome these challenges, better drug delivery systems need to be developed. Recently, micro systems have emerged as promising candidates to solve the challenges of poor solubility, low......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...

  7. Drug loading and release on tumor cells using silk fibroin–albumin nanoparticles as carriers

    International Nuclear Information System (INIS)

    Subia, B; Kundu, S C

    2013-01-01

    Polymeric and biodegradable nanoparticles are frequently used in drug delivery systems. In this study silk fibroin–albumin blended nanoparticles were prepared using the desolvation method without any surfactant. These nanoparticles are easily internalized by the cells, reside within perinuclear spaces and act as carriers for delivery of the model drug methotrexate. Methotrexate loaded nanoparticles have better encapsulation efficiency, drug loading ability and less toxicity. The in vitro release behavior of methotrexate from the nanoparticles suggests that about 85% of the drug gets released after 12 days. The encapsulation and loading of a drug would depend on factors such as size, charge and hydrophobicity, which affect drug release. MTT assay and conjugation of particles with FITC demonstrate that the silk fibroin–albumin nanoparticles do not affect the viability and biocompatibility of cells. This blended nanoparticle, therefore, could be a promising nanocarrier for the delivery of drugs and other bioactive molecules. (paper)

  8. Arginine-based biodegradable ether-ester polymers with low cytotoxicity as potential gene carriers.

    Science.gov (United States)

    Memanishvili, Tamar; Zavradashvili, Nino; Kupatadze, Nino; Tugushi, David; Gverdtsiteli, Marekh; Torchilin, Vladimir P; Wandrey, Christine; Baldi, Lucia; Manoli, Sagar S; Katsarava, Ramaz

    2014-08-11

    The success of gene therapy depends on safe and effective gene carriers. Despite being widely used, synthetic vectors based on poly(ethylenimine) (PEI), poly(l-lysine) (PLL), or poly(l-arginine) (poly-Arg) are not yet fully satisfactory. Thus, both improvement of established carriers and creation of new synthetic vectors are necessary. A series of biodegradable arginine-based ether-ester polycations was developed, which consists of three main classes: amides, urethanes, and ureas. Compared to that of PEI, PLL, and poly-Arg, much lower cytotoxicity was achieved for the new cationic arginine-based ether-ester polymers. Even at polycation concentrations up to 2 mg/mL, no significant negative effect on cell viability was observed upon exposure of several cell lines (murine mammary carcinoma, human cervical adenocarcinoma, murine melanoma, and mouse fibroblast) to the new polymers. Interaction with plasmid DNA yielded compact and stable complexes. The results demonstrate the potential of arginine-based ether-ester polycations as nonviral carriers for gene therapy applications.

  9. Preparation and application of functionalized nano drug carriers

    OpenAIRE

    Gong, Rudong; Chen, Gaimin

    2016-01-01

    Objective: Targeting at category memory characteristics and preparation methods of functionalized nano drugs, preparation technology of functionalized nano drug carriers is studied, and then important role of functionalized nano drug carrier in preparation of medicine is studied. Methods: Carry out the relevant literature search with computer, change limited language in the paper to Chinese and necessarily remove repetitive studies. Results: After first review of 1260 retrieved literature, it...

  10. A facile method to prepare superparamagnetic iron oxide and hydrophobic drug-encapsulated biodegradable polyurethane nanoparticles

    Directory of Open Access Journals (Sweden)

    Cheng K

    2017-03-01

    Full Text Available Kuo-Wei Cheng, Shan-hui Hsu Institute of Polymer Science and Engineering, College of Engineering, National Taiwan University, Taipei, Taiwan, Republic of China Abstract: Superparamagnetic iron oxide nanoparticles (SPIO NPs have a wide range of biomedical applications such as in magnetic resonance imaging, targeting, and hyperthermia therapy. Aggregation of SPIO NPs can occur because of the hydrophobic surface and high surface energy of SPIO NPs. Here, we developed a facile method to encapsulate SPIO NPs in amphiphilic biodegradable polymer. Anionic biodegradable polyurethane nanoparticles (PU NPs with ~35 nm size and different chemistry were prepared by waterborne processes. SPIO NPs were synthesized by chemical co-precipitation. SPIO NPs were then added to the aqueous dispersion of PU NPs, followed by application of high-frequency (~20 kHz ultrasonic vibration for 3 min. This method rendered SPIO-PU hybrid NPs (size ~110 nm suspended in water. SPIO-PU hybrid NPs contained ~50–60 wt% SPIO and retained the superparamagnetic property (evaluated by a magnetometer as well as high contrast in magnetic resonance imaging. SPIO-PU NPs also showed the ability to provide cell hyperthermic treatment. Using the same ultrasonic method, hydrophobic drug (Vitamin K3 [VK3] or (9-(methylaminomethylanthracene [MAMA] could also be encapsulated in PU NPs. The VK3-PU or MAMA-PU hybrid NPs had ~35 nm size and different release profiles for PUs with different chemistry. The encapsulation efficiency for VK3 and MAMA was high (~95% without burst release. The encapsulation mechanism may be attributed to the low glass transition temperature (Tg and good mechanical compliance of PU NPs. The new encapsulation method involving waterborne biodegradable PU NPs is simple, rapid, and effective to produce multimodular NP carriers. Keywords: superparamagnetic iron oxide, polyurethane, drug release, hybrid nanoparticles

  11. Hybrid Mesoporous Silica-Based Drug Carrier Nanostructures with Improved Degradability by Hydroxyapatite.

    Science.gov (United States)

    Hao, Xiaohong; Hu, Xixue; Zhang, Cuimiao; Chen, Shizhu; Li, Zhenhua; Yang, Xinjian; Liu, Huifang; Jia, Guang; Liu, Dandan; Ge, Kun; Liang, Xing-Jie; Zhang, Jinchao

    2015-10-27

    Potential bioaccumulation is one of the biggest limitations for silica nanodrug delivery systems in cancer therapy. In this study, a mesoporous silica nanoparticles/hydroxyapatite (MSNs/HAP) hybrid drug carrier, which enhanced the biodegradability of silica, was developed by a one-step method. The morphology and structure of the nanoparticles were characterized by TEM, DLS, FT-IR, XRD, N2 adsorption-desorption isotherms, and XPS, and the drug loading and release behaviors were tested. TEM and ICP-OES results indicate that the degradability of the nanoparticles has been significantly improved by Ca(2+) escape from the skeleton in an acid environment. The MSNs/HAP sample exhibits a higher drug loading content of about 5 times that of MSNs. The biological experiment results show that the MSNs/HAP not only exhibits good biocompatibility and antitumor effect but also greatly reduces the side effects of free DOX. The as-synthesized hybrid nanoparticles may act as a promising drug delivery system due to their good biocompatibility, high drug loading efficiency, pH sensitivity, and excellent biodegradability.

  12. Advantages and disadvantages of biodegradable platforms in drug eluting stents.

    Science.gov (United States)

    Rodriguez-Granillo, Agustina; Rubilar, Bibiana; Rodriguez-Granillo, Gaston; Rodriguez, Alfredo E

    2011-03-26

    Coronary angioplasty with drug-eluting stent (DES) implantation is currently the most common stent procedure worldwide. Since the introduction of DES, coronary restenosis as well as the incidence of target vessel and target lesion revascularization have been significantly reduced. However, the incidence of very late stent thrombosis beyond the first year after stent deployment has more commonly been linked to DES than to bare-metal stent (BMS) implantation. Several factors have been associated with very late stent thrombosis after DES implantation, such as delayed healing, inflammation, stent mal-apposition and endothelial dysfunction. Some of these adverse events were associated with the presence of durable polymers, which were essential to allow the elution of the immunosuppressive drug in the first DES designs. The introduction of erodable polymers in DES technology has provided the potential to complete the degradation of the polymer simultaneously or immediately after the release of the immunosuppressive drug, after which a BMS remains in place. Several DES designs with biodegradable (BIO) polymers have been introduced in preclinical and clinical studies, including randomized trials. In this review, we analyze the clinical results from 6 observational and randomized studies with BIO polymers and discuss advantages and disadvantages of this new technology.

  13. Perfluorocarbon (PFC) emulsions as potential drug carriers

    International Nuclear Information System (INIS)

    Yuhas, J.M.; Goodman, R.L.; Moore, R.E.

    1984-01-01

    PFC emulsions have excellent oxygen transporting properties and have been reported to enhance the response of murine tumors to both radiation and BCNU. While the presently available emulsions are far too toxic to the immune system to be used in cancer therapy, they can be used to investigate the overall potential of this approach. As an example, the authors have found that these emulsions can alter drug availability. The lipophilicity of both the PFC and the drug in question determine the partitioning of the drug between the organic and aqueous phases of an emulsion. In vitro, this can reduce drug effectiveness by reducing the amount of drug available to the cells. In vivo, however, this partitioning may produce sustained drug exposure, which could be of benefit in cancer therapy and other applications. In brief, as the drug is absorbed from the circulating aqueous phase, additional drug would leach from the PFC, thereby providing a sustained drug exposure similar to that obtained with liposomes. While a great deal more work will be required to evaluate the practicality of this approach, the existence of this phenomenon must be taken into account in both the design and interpretation of efficacy studies in which anesthetics, chemotherapeutics, etc are employed

  14. Semiconducting, biodegradable and bioactive fibers for drug delivery

    Directory of Open Access Journals (Sweden)

    M. M. Perez-Madrigal

    2016-08-01

    Full Text Available In this work we present the drug release properties and morphological studies of fibers formed by mixing different ratios of poly(lactic acid (PLA and poly(3-thiophene methyl acetate (P3TMA loaded with four drugs (ciprofloxacin, chlorhexidine dihydrochloride, triclosan and ibuprofen sodium salt. Thus, the main aim of this study is to prove that the excellent cellular response of PLA-P3TMA biocompatible scaffolds can be successfully combined with essential applications as drug carrier and delivery systems. Atomic force microscopic (AFM and scanning electron microscopic (SEM micrographs of PLA-P3TMA fibers indicate that the presence of the conducting polymer inside the PLA matrix affects the surface morphology, resulting in a significant increment of the bulk conductivity with respect to PLA fibers. Electrospun hybrid fibers of PLA and P3TMA successfully load both hydrophilic and hydrophobic drugs, the release profiles depending on the release environment (i.e. the release rate increases with the hydrophobicity of the medium. Finally, our results prove that the antibacterial activity of the drugs is not affected by their interactions with the PLA-P3TMA matrix.

  15. Biodegradable poly (lactic acid-co-glycolic acid) scaffolds as carriers for genetically-modified fibroblasts.

    Science.gov (United States)

    Perisic, Tatjana; Zhang, Ziyang; Foehr, Peter; Hopfner, Ursula; Klutz, Kathrin; Burgkart, Rainer H; Slobodianski, Alexei; Goeldner, Moritz; Machens, Hans-Günther; Schilling, Arndt F

    2017-01-01

    Recent advances in gene delivery into cells allow improved therapeutic effects in gene therapy trials. To increase the bioavailability of applied cells, it is of great interest that transfected cells remain at the application site and systemic spread is minimized. In this study, we tested clinically used biodegradable poly(lactic acid-co-glycolic acid) (PLGA) scaffolds (Vicryl & Ethisorb) as transient carriers for genetically modified cells. To this aim, we used human fibroblasts and examined attachment and proliferation of untransfected cells on the scaffolds in vitro, as well as the mechanical properties of the scaffolds at four time points (1, 3, 6 and 9 days) of cultivation. Furthermore, the adherence of cells transfected with green fluorescent protein (GFP) and vascular endothelial growth factor (VEGF165) and also VEGF165 protein secretion were investigated. Our results show that human fibroblasts adhere on both types of PLGA scaffolds. However, proliferation and transgene expression capacity were higher on Ethisorb scaffolds most probably due to a different architecture of the scaffold. Additionally, cultivation of the cells on the scaffolds did not alter their biomechanical properties. The results of this investigation could be potentially exploited in therapeutic regiments with areal delivery of transiently transfected cells and may open the way for a variety of applications of cell-based gene therapy, tissue engineering and regenerative medicine.

  16. Biodegradable poly (lactic acid-co-glycolic acid scaffolds as carriers for genetically-modified fibroblasts.

    Directory of Open Access Journals (Sweden)

    Tatjana Perisic

    Full Text Available Recent advances in gene delivery into cells allow improved therapeutic effects in gene therapy trials. To increase the bioavailability of applied cells, it is of great interest that transfected cells remain at the application site and systemic spread is minimized. In this study, we tested clinically used biodegradable poly(lactic acid-co-glycolic acid (PLGA scaffolds (Vicryl & Ethisorb as transient carriers for genetically modified cells. To this aim, we used human fibroblasts and examined attachment and proliferation of untransfected cells on the scaffolds in vitro, as well as the mechanical properties of the scaffolds at four time points (1, 3, 6 and 9 days of cultivation. Furthermore, the adherence of cells transfected with green fluorescent protein (GFP and vascular endothelial growth factor (VEGF165 and also VEGF165 protein secretion were investigated. Our results show that human fibroblasts adhere on both types of PLGA scaffolds. However, proliferation and transgene expression capacity were higher on Ethisorb scaffolds most probably due to a different architecture of the scaffold. Additionally, cultivation of the cells on the scaffolds did not alter their biomechanical properties. The results of this investigation could be potentially exploited in therapeutic regiments with areal delivery of transiently transfected cells and may open the way for a variety of applications of cell-based gene therapy, tissue engineering and regenerative medicine.

  17. P-glycoprotein targeted nanoscale drug carriers

    KAUST Repository

    Li, Wengang

    2013-02-01

    Multi-drug resistance (MDR) is a trend whereby tumor cells exposed to one cytotoxic agent develop cross-resistance to a range of structurally and functionally unrelated compounds. P -glycoprotein (P -gp) efflux pump is one of the mostly studied drug carrying processes that shuttle the drugs out of tumor cells. Thus, P -gp inhibitors have attracted a lot of attention as they can stop cancer drugs from being pumped out of target cells with the consumption of ATP. Using quantitive structure activity relationship (QSAR), we have successfully synthesized a series of novel P -gp inhibitors. The obtained dihydropyrroloquinoxalines series were fully characterized and then tested against bacterial and tumor assays with over-expressed P -gps. All compounds were bioactive especially compound 1c that had enhanced antibacterial activity. Furthermore, these compounds were utilized as targeting vectors to direct drug delivery vehicles such as silica nanoparticles (SNPs) to cancerous Hela cells with over expressed P -gps. Cell uptake studies showed a successful accumulation of these decorated SNPs in tumor cells compared to undecorated SNPs. The results obtained show that dihydropyrroloquinoxalines constitute a promising drug candidate for targeting cancers with MDR. Copyright © 2013 American Scientific Publishers All rights reserved.

  18. Drug-laden 3D biodegradable label using QR code for anti-counterfeiting of drugs.

    Science.gov (United States)

    Fei, Jie; Liu, Ran

    2016-06-01

    Wiping out counterfeit drugs is a great task for public health care around the world. The boost of these drugs makes treatment to become potentially harmful or even lethal. In this paper, biodegradable drug-laden QR code label for anti-counterfeiting of drugs is proposed that can provide the non-fluorescence recognition and high capacity. It is fabricated by the laser cutting to achieve the roughness over different surface which causes the difference in the gray levels on the translucent material the QR code pattern, and the micro mold process to obtain the drug-laden biodegradable label. We screened biomaterials presenting the relevant conditions and further requirements of the package. The drug-laden microlabel is on the surface of the troches or the bottom of the capsule and can be read by a simple smartphone QR code reader application. Labeling the pill directly and decoding the information successfully means more convenient and simple operation with non-fluorescence and high capacity in contrast to the traditional methods. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Drug Carrier for Photodynamic Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Tilahun Ayane Debele

    2015-09-01

    Full Text Available Photodynamic therapy (PDT is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS, and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0 to an excited singlet state (S1–Sn, followed by intersystem crossing to an excited triplet state (T1. The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*, which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer.

  20. Drug Carrier for Photodynamic Cancer Therapy

    Science.gov (United States)

    Debele, Tilahun Ayane; Peng, Sydney; Tsai, Hsieh-Chih

    2015-01-01

    Photodynamic therapy (PDT) is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS), and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0) to an excited singlet state (S1–Sn), followed by intersystem crossing to an excited triplet state (T1). The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*), which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer. PMID:26389879

  1. Preparation and application of functionalized nano drug carriers.

    Science.gov (United States)

    Gong, Rudong; Chen, Gaimin

    2016-05-01

    Targeting at category memory characteristics and preparation methods of functionalized nano drugs, preparation technology of functionalized nano drug carriers is studied, and then important role of functionalized nano drug carrier in preparation of medicine is studied. Carry out the relevant literature search with computer, change limited language in the paper to Chinese and necessarily remove repetitive studies. After first review of 1260 retrieved literature, it can be found that nano drug is with accurate quantity, relatively good targeting, specificity and absorbency. Necessary research of nano drug carriers can prevent and treat disease to a certain extent. Preparation of functionalized nanocarrier is simple and convenient, which can improve frequency of use of nano preparation technology and provide better development space for medical use. Therefore, nanocarriers should be combined with drugs with relatively strong specificity in clinics, in order to be able to conduct effective research on nanometer intelligent drug, effectively promote long-term development of nano biotechnology, and then provide favorable, reliable basis for clinical diagnosis and treatment.

  2. DNA origami as a carrier for circumvention of drug resistance.

    Science.gov (United States)

    Jiang, Qiao; Song, Chen; Nangreave, Jeanette; Liu, Xiaowei; Lin, Lin; Qiu, Dengli; Wang, Zhen-Gang; Zou, Guozhang; Liang, Xingjie; Yan, Hao; Ding, Baoquan

    2012-08-15

    Although a multitude of promising anti-cancer drugs have been developed over the past 50 years, effective delivery of the drugs to diseased cells remains a challenge. Recently, nanoparticles have been used as drug delivery vehicles due to their high delivery efficiencies and the possibility to circumvent cellular drug resistance. However, the lack of biocompatibility and inability to engineer spatially addressable surfaces for multi-functional activity remains an obstacle to their widespread use. Here we present a novel drug carrier system based on self-assembled, spatially addressable DNA origami nanostructures that confronts these limitations. Doxorubicin, a well-known anti-cancer drug, was non-covalently attached to DNA origami nanostructures through intercalation. A high level of drug loading efficiency was achieved, and the complex exhibited prominent cytotoxicity not only to regular human breast adenocarcinoma cancer cells (MCF 7), but more importantly to doxorubicin-resistant cancer cells, inducing a remarkable reversal of phenotype resistance. With the DNA origami drug delivery vehicles, the cellular internalization of doxorubicin was increased, which contributed to the significant enhancement of cell-killing activity to doxorubicin-resistant MCF 7 cells. Presumably, the activity of doxorubicin-loaded DNA origami inhibits lysosomal acidification, resulting in cellular redistribution of the drug to action sites. Our results suggest that DNA origami has immense potential as an efficient, biocompatible drug carrier and delivery vehicle in the treatment of cancer.

  3. Carbon Nanotubes: An Emerging Drug Carrier for Targeting Cancer Cells

    Science.gov (United States)

    Bhattacharya, Shiv Sankar; Mishra, Arun Kumar; Verma, Navneet; Verma, Anurag; Pandit, Jayanta Kumar

    2014-01-01

    During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review. PMID:24872894

  4. GELATIN CARRIERS FOR DRUG AND CELL DELIVERY IN TISSUE ENGINEERING

    OpenAIRE

    Santoro, Marco; Tatara, Alexander M.; Mikos, Antonios G.

    2014-01-01

    The ability of gelatin to form complexes with different drugs has been investigated for controlled release applications. Gelatin parameters, such as crosslinking density and isoelectric point, have been tuned in order to optimize gelatin degradation and drug delivery kinetics. In recent years, focus has shifted away from the use of gelatin in isolation towards the modification of gelatin with functional groups and the fabrication of material composites with embedded gelatin carriers. In this ...

  5. Conjugate of doxorubicin with a thermosensitive polymer drug carrier

    Czech Academy of Sciences Publication Activity Database

    Chytrý, Vladimír; Ulbrich, Karel

    2001-01-01

    Roč. 16, č. 6 (2001), s. 427-440 ISSN 0883-9115 R&D Projects: GA ČR GV307/96/K226 Institutional research plan: CEZ:AV0Z4050913 Keywords : doxorubicin * thermosensitive drug carriers * cloud point of polymer solutions Subject RIV: CD - Macromolecular Chemistry Impact factor: 0.571, year: 2001

  6. Implant-associated local drug delivery systems based on biodegradable polymers: customized designs for different medical applications.

    Science.gov (United States)

    Sternberg, Katrin; Petersen, Svea; Grabow, Niels; Senz, Volkmar; Meyer zu Schwabedissen, Henriette; Kroemer, Heyo K; Schmitz, Klaus-Peter

    2013-10-01

    Implants providing controlled, local release of active substances are of interest in different medical applications. Therefore, the focus of the present article is the development of implant-associated diffusion- or chemically controlled local drug delivery (LDD) systems based on biodegradable polymeric drug carriers. In this context, we provide new data and review our own recently published data concerning the drug release behavior of diffusion-controlled LDD systems in relation to the kind of polymer, drug content, coating mass/thickness, and layer composition. We demonstrate that polymers allow a wide range of control over the drug release characteristics. In this regard, we show that the glass transition temperature of a polymer has an impact on its drug release. Additionally, the blending of hydrophobic, semicrystalline polymers with amorphous polymers leads to an increase in the rate of drug release compared with the pure semicrystalline polymer. Moreover, the percentage loading of the embedded drug has a considerable effect on the rate and duration of drug release. Furthermore, we discuss chemically controlled LDD systems designed for the release of biomolecules, such as growth factors, as well as nanoparticle-mediated LDD systems. With our own published data on drug-eluting stents, microstents, and cochlear implants, we highlight exemplary implant-associated LDD systems designed to improve implant performance through the reduction of undesirable effects such as in-stent restenosis and fibrosis.

  7. PLGA based drug delivery systems: Promising carriers for wound healing activity.

    Science.gov (United States)

    Chereddy, Kiran Kumar; Vandermeulen, Gaëlle; Préat, Véronique

    2016-03-01

    Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Current treatment options are limited and require repeated administrations which led to the development of new therapeutics to satisfy the unmet clinical needs. Many potent wound healing agents were discovered but most of them are fragile and/or sensitive to in vivo conditions. Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable polymer approved by food and drug administration and European medicines agency as an excipient for parenteral administrations. It is a well-established drug delivery system in various medical applications. The aim of the current review is to elaborate the applications of PLGA based drug delivery systems carrying different wound healing agents and also present PLGA itself as a wound healing promoter. PLGA carriers encapsulating drugs such as antibiotics, anti-inflammatory drugs, proteins/peptides, and nucleic acids targeting various phases/signaling cycles of wound healing, are discussed with examples. The combined therapeutic effects of PLGA and a loaded drug on wound healing are also mentioned. © 2016 by the Wound Healing Society.

  8. Polymer carriers for targeted drug delivery and controlled drug release

    Czech Academy of Sciences Publication Activity Database

    Ulbrich, Karel; Pechar, Michal; Etrych, Tomáš; Jelínková, Markéta; Kovář, Marek; Říhová, Blanka

    2003-01-01

    Roč. 10, č. 1 (2003), s. 3-4 ISSN 1211-5894 R&D Projects: GA ČR GA305/02/1425; GA AV ČR IAA4050201 Institutional research plan: CEZ:AV0Z5020903; CEZ:AV0Z4050913 Keywords : HPMA copolymers * drug targeting * drug delivery Subject RIV: CD - Macromolecular Chemistry

  9. Polysaccharide based nanogels in the drug delivery system: Application as the carrier of pharmaceutical agents.

    Science.gov (United States)

    Debele, Tilahun Ayane; Mekuria, Shewaye Lakew; Tsai, Hsieh-Chih

    2016-11-01

    Polysaccharide-based nanoparticles have fascinated attention as a vesicle of different pharmaceutical agents due to their unique multi-functional groups in addition to their physicochemical properties, including biocompatibility and biodegradability. The existence of multi-functional groups on the polysaccharide backbone permits facile chemical or biochemical modification to synthesize polysaccharide based nanoparticles with miscellaneous structures. Polysaccharide-based nanogels have high water content, large surface area for multivalent bioconjugation, tunable size, and interior network for the incorporation of different pharmaceutical agents. These unique properties offer great potential for the utilization of polysaccharide-based nanogels in the drug delivery systems. Hence, this review describes chemistry of certain common polysaccharides, several methodologies used to synthesize polysaccharide nanoparticles and primarily focused on the polysaccharide (or polysaccharide derivative) based nanogels as the carrier of pharmaceutical agents. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Antimicrobial drug susceptibility of Neisseria meningitidis strains isolated from carriers

    Directory of Open Access Journals (Sweden)

    Dayamí García

    2000-06-01

    Full Text Available When it is necessary to determine the susceptibility of Neisseria meningitidis (Nm strains to antimicrobial drugs, it is important to consider that it should be analyzed in a double context. One of them related to the use of drugs in a specific medical treatment; and the other; to chemoprophylatic drugs, both with the same purpose: the accurate selection of the “in vivo” antimicrobial agent. This requires the study of the sensitivity and resistance of strains isolated in both carriers and patients. With the aim of further studying the behavior of the strains that currently circulate in Cuba, an antimicrobial drug susceptibility study was conducted in 90 strains isolated from carriers during the first half of 1998. The agar dilution method was used to determine the minimum inhibitory concentrations (MICs to: penicillin, ampicillin, rifampin, sulfadiazine, chloramphenicol, ciprofloxacin, ceftriaxone, cefotaxime. The study of the three latter drugs was done for the first time in our country. The search for β- lactamase-producer strains was also performed. There was a predominance of penicillin sensitive strains (82,2% with an intermediate sensitivity to ampicillin (57,8%, while 70% of the strains were sensitive to sulfadiazine. Regarding the rest of the antimicrobial drugs, 100% of the strains were sensitive. The paper shows the MICs for each drug as well as the phenotypic characteristics of the strains with the penicillin and sulfadiazine sensitivity and resistance patterns. No β-lactamase-producer strains were found.

  11. Drug carrier in cancer therapy: A simulation study based on magnetic carrier substances

    Science.gov (United States)

    Adam, Tijjani; Dhahi, Th S.; Mohammed, Mohammed; Hashim, U.; Noriman, N. Z.; Dahham, Omar S.

    2017-09-01

    The principle of magnetic carrier is a medium for transferring information by sending the drug to the specific part to kill tumor cells. Generally, there are seven stages of cancer. Most of the patient with cancer can only be detected when reaches stage four. At that stage, the cancer is difficult to destroy or to cure. Comparing to the nearly stage, there are probability to destroy tumor cell completely by sending the drug through magnetic carrier directly to nerve. Another way to destroyed tumor completely is by using Deoxyribonucleic acid (DNA). This project is about the simulation study based on magnetic carrier substances. The COMSOL multiphysic software is used in this project. The simulation model represents a permanent magnet, blood vessel, surrounding tissues and air in 2D. Based on result obtained, the graph shown during sending the magnetic flux is high. However, as its carry information the magnetic flux reducess from the above, the move from 0m until 0.009 m it become the lowers and start increase the flux from this until maximum at 0.018m. This is due the fact that carrier start to increase after because the low information is gradually reduce until 0.018m.

  12. 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

  13. Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Warangkana Lohcharoenkal

    2014-01-01

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

  14. Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

    Science.gov (United States)

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

    2014-01-01

    Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy. PMID:24772414

  15. Biodegradable Oxamide-Phenylene-Based Mesoporous Organosilica Nanoparticles with Unprecedented Drug Payloads for Delivery in Cells

    KAUST Repository

    Croissant, Jonas

    2016-06-03

    We describe biodegradable mesoporous hybrid NPs in the presence of proteins, and its application for drug delivery. We synthesized oxamide-phenylene-based mesoporous organosilica nanoparticles (MON) in the absence of silica source which had a remarkably high organic content with a high surface area. Oxamide functions provided biodegradability in the presence of trypsin model proteins. MON displayed exceptionally high payloads of hydrophilic and hydrophobic drugs (up to 84 wt%), and a unique zero premature leakage without the pore capping, unlike mesoporous silica. MON were biocompatible and internalized into cancer cells for drug delivery.

  16. INTERPOLYELECTROLYTE COMPLEXES AS PROSPECTIVE CARRIERS FOR CONTROLLED DRUG DELIVERY

    OpenAIRE

    Kaur Jasmeet; Harikumar S.L.; Kaur Amanpreet

    2012-01-01

    In the current scenario, polymers as carriers have revolutionized the drug delivery system. A more successful approach, to exploit the different properties of polymers in a solitary system is the complexation of polymers to form polyelectrolyte complexes. These complexes circumvent the use of chemical crosslinking agents, thereby reducing the risk of toxicity. The complex formed is generally applied in different dosage forms for the formulation of stable aggregated macromolecules. There are t...

  17. Design of starch functionalized biodegradable P(MAA-co-MMA) as carrier matrix for l-asparaginase immobilization.

    Science.gov (United States)

    Ulu, Ahmet; Koytepe, Suleyman; Ates, Burhan

    2016-11-20

    We prepared biodegradable P(MAA-co-MMA)-starch composite as carrier matrix for the immobilization of l-asparaginase (l-ASNase), an important chemotherapeutic agent in acute lymphoblastic leukemia. Chemical characteristics and thermal stability of the prepared composites were determined by FT-IR, TGA, DTA and, DSC, respectively. Also, biodegradability measurements of P(MAA-co-MMA)-starch composites were carried out to examine the effects of degradation of the starch. Then, l-ASNase was immobilized on the P(MAA-co-MMA)-starch composites. The surface morphology of the composite before and after immobilization was characterized by SEM, EDX, and AFM. The properties of the immobilized l-ASNase were investigated and compared with the free enzyme. The immobilized l-ASNase had better showed thermal and pH stability, and remained stable after 30days of storage at 25°C. Thus, based on the findings of the present work, the P(MAA-co-MMA)-starch composite can be exploited as the biocompatible matrix used for l-ASNase immobilization for medical applications due to biocompatibility and biodegradability. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Drug release control in delivery system for biodegradable polymer drugs by γ-radiation

    International Nuclear Information System (INIS)

    Yoshioka, Sumie; Azo, Yukio; Kojima, Shigeo

    1997-01-01

    Characterizations of the drug release from microsphere and hydrogel preparation made from biodegradable polymers were investigated aiming at development of a drug delivery system which allows an optimum drug delivery and the identification of the factors which control its delivery. Poly-lactic acid microspheres containing 10% of progesterone were produced from poly DL-lactic acid and exposed to γ-ray at 5-1000 kGy. And its glass transition temperature (Tg) was determined by differential scanning calorimetry. The temperature was gradually lowered with an increase in the dose of radiation. Tg of the microsphere exposed at 1000 kGy was lower by 10degC compared with the untreated one, showing that Tg control is possible without changing the size distribution of microsphere. Then, the amount of progesterone released from microsphere was determined. The release rate of the drug linearly increased with a square root of radiation time. These results indicate that the control of drug release rate is possible through controling the microsphere's Tg by γ-ray radiation. (M.N.)

  19. Biocompatibility of Chitosan Carriers with Application in Drug Delivery

    Directory of Open Access Journals (Sweden)

    Ana Grenha

    2012-09-01

    Full Text Available Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures.

  20. GELATIN CARRIERS FOR DRUG AND CELL DELIVERY IN TISSUE ENGINEERING

    Science.gov (United States)

    Santoro, Marco; Tatara, Alexander M.; Mikos, Antonios G.

    2014-01-01

    The ability of gelatin to form complexes with different drugs has been investigated for controlled release applications. Gelatin parameters, such as crosslinking density and isoelectric point, have been tuned in order to optimize gelatin degradation and drug delivery kinetics. In recent years, focus has shifted away from the use of gelatin in isolation towards the modification of gelatin with functional groups and the fabrication of material composites with embedded gelatin carriers. In this review, we highlight some of the latest work being performed in these areas and comment on trends in the field. Specifically, we discuss gelatin modifications for immune system evasion, drug stabilization, and targeted delivery, as well as gelatin composite systems based on ceramics, naturally-occurring polymers, and synthetic polymers. PMID:24746627

  1. Carrier-free, functionalized pure drug nanorods as a novel cancer-targeted drug delivery platform

    Science.gov (United States)

    Li, Yanan; Yang, Yinlong; An, Feifei; Liu, Zhuang; Zhang, Xiujuan; Zhang, Xiaohong

    2013-01-01

    A one-dimensional drug delivery system (1D DDS) is highly attractive since it has distinct advantages such as enhanced drug efficiency and better pharmacokinetics. However, drugs in 1D DDSs are all encapsulated in inert carriers, and problems such as low drug loading content and possible undesirable side effects caused by the carriers remain a serious challenge. In this paper, a novel, carrier-free, pure drug nanorod-based, tumor-targeted 1D DDS has been developed. Drugs are first prepared as nanorods and then surface functionalized to achieve excellent water dispersity and stability. The resulting drug nanorods show enhanced internalization rates mainly through energy-dependent endocytosis, with the shape-mediated nanorod (NR) diffusion process as a secondary pathway. The multiple endocytotic mechanisms lead to significantly improved drug efficiency of functionalized NRs with nearly ten times higher cytotoxicity than those of free molecules and unfunctionalized NRs. A targeted drug delivery system can be readily achieved through surface functionalization with targeting group linked amphipathic surfactant, which exhibits significantly enhanced drug efficacy and discriminates between cell lines with high selectivity. These results clearly show that this tumor-targeting DDS demonstrates high potential toward specific cancer cell lines.

  2. Carrier-free, functionalized pure drug nanorods as a novel cancer-targeted drug delivery platform

    International Nuclear Information System (INIS)

    Li Yanan; An Feifei; Zhang Xiaohong; Yang Yinlong; Liu Zhuang; Zhang Xiujuan

    2013-01-01

    A one-dimensional drug delivery system (1D DDS) is highly attractive since it has distinct advantages such as enhanced drug efficiency and better pharmacokinetics. However, drugs in 1D DDSs are all encapsulated in inert carriers, and problems such as low drug loading content and possible undesirable side effects caused by the carriers remain a serious challenge. In this paper, a novel, carrier-free, pure drug nanorod-based, tumor-targeted 1D DDS has been developed. Drugs are first prepared as nanorods and then surface functionalized to achieve excellent water dispersity and stability. The resulting drug nanorods show enhanced internalization rates mainly through energy-dependent endocytosis, with the shape-mediated nanorod (NR) diffusion process as a secondary pathway. The multiple endocytotic mechanisms lead to significantly improved drug efficiency of functionalized NRs with nearly ten times higher cytotoxicity than those of free molecules and unfunctionalized NRs. A targeted drug delivery system can be readily achieved through surface functionalization with targeting group linked amphipathic surfactant, which exhibits significantly enhanced drug efficacy and discriminates between cell lines with high selectivity. These results clearly show that this tumor-targeting DDS demonstrates high potential toward specific cancer cell lines. (paper)

  3. Chiral Analysis of Pesticides and Drugs of Environmental Concern: Biodegradation and Enantiomeric Fraction

    Directory of Open Access Journals (Sweden)

    Alexandra S. Maia

    2017-09-01

    Full Text Available The importance of stereochemistry for medicinal chemistry and pharmacology is well recognized and the dissimilar behavior of enantiomers is fully documented. Regarding the environment, the significance is equivalent since enantiomers of chiral organic pollutants can also differ in biodegradation processes and fate, as well as in ecotoxicity. This review comprises designed biodegradation studies of several chiral drugs and pesticides followed by enantioselective analytical methodologies to accurately measure the enantiomeric fraction (EF. The enantioselective monitoring of microcosms and laboratory-scale experiments with different environmental matrices is herein reported. Thus, this review focuses on the importance of evaluating the EF variation during biodegradation studies of chiral pharmaceuticals, drugs of abuse, and agrochemicals and has implications for the understanding of the environmental fate of chiral pollutants.

  4. Albumin-crosslinked alginate hydrogels as sustained drug release carrier

    International Nuclear Information System (INIS)

    Tada, Daisuke; Tanabe, Toshizumi; Tachibana, Akira; Yamauchi, Kiyoshi

    2007-01-01

    To take advantage of the drug-binding ability of albumin as a component of drug delivery system, we have prepared hydrogels consisting of alginic acid (AL) and recombinant human serum albumin (rHSA) by dehydrating condensation using N-hydroxysuccininimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. As rHSA content increased, the swelling ratio of the hydrogel decreased, indicating rHSA functioned as a crosslinker. In fact, trypsin treatment solubilized the hydrogel. Salicylic acid, which has high affinity for rHSA, was loaded most on the hydrogel of the highest rHSA content despite the lowest swelling ratio. Meanwhile, drugs with less affinity for HSA such as o-anisic acid and benzoic acid were preferably loaded on the hydrogel having the highest swelling ratio but the lowest HSA content. The release of salicylic acid from the hydrogel sustained longer than o-anisic acid and benzoic acid, reflecting the affinity of the drug for HSA. Furthermore, the hydrogel could carry much of positively charged dibucaine by the interaction with anionic alginic acid and showed highly sustained release. Since the safety of AL and rHSA in medical use is guaranteed, rHSA-crosslinked AL hydrogel is expected to use as a sustained drug release carrier for drugs having affinity for HSA and those with cationic charge

  5. Effect of drug solubility and lipid carrier on drug release from lipid nanoparticles for dermal delivery.

    Science.gov (United States)

    Zoubari, Gaith; Staufenbiel, Sven; Volz, Pierre; Alexiev, Ulrike; Bodmeier, Roland

    2017-01-01

    Lipid nanoparticles have gained increased interest in the field of dermal products because of various advantages such as improved drug absorption and controlled drug release. The main objective was to investigate the influence of drug solubility and type of lipid carrier on the in vitro drug release. Drugs of different solubilities in the release medium PBS pH 7.4 (dexamethasone: 0.1mg/ml and diclofenac sodium: 5.0mg/ml) and three different lipids (in which the drugs had the highest solubility), Gelucire® 50/13 (solid lipid, mp: 50°C), Witepsol® S55 (solid lipid, mp: 33.5-35.5°C) and Capryol® 90 (liquid lipid) were chosen. The lipid nanoparticles were prepared by high shear homogenization. All nanosuspensions were in the nanometer range (up to 400nm) and the drug encapsulation efficiency was between 84% and 95%. The drug release was prolonged over 48h without an initial burst release and was dependent on the lipid carrier. Formulations containing a higher amount of solid Gelucire® 50/13 released the drugs slower due to the high affinity of the drugs to this lipid product. Inclusion of the liquid lipid Capryol® 90 resulted in a less organized lipidic structures (softer particles) and therefore a faster drug release. Despite its higher water solubility, diclofenac was released slower than dexamethasone because of its higher solubility in the lipid carriers. DSC studies indicated a partial miscibility between the solid lipids and a good miscibility between the solid and liquid lipids. Primary studies using total internal reflection fluorescence (TIRF) microscopy indicated that it is possible to detect individual fluorescently labeled dexamethasone (DXM-F) molecules dissolved in the liquid lipid Capryol® 90. These studies will allow for the precise determination of the drug distribution within the lipid carrier, and the changes upon drug release. In conclusion, lipid carrier type and drug solubility in the lipid have a large influence on the in vitro drug

  6. Critical evaluation of biodegradable polymers used in nanodrugs

    Science.gov (United States)

    Marin, Edgar; Briceño, Maria Isabel; Caballero-George, Catherina

    2013-01-01

    Use of biodegradable polymers for biomedical applications has increased in recent decades due to their biocompatibility, biodegradability, flexibility, and minimal side effects. Applications of these materials include creation of skin, blood vessels, cartilage scaffolds, and nanosystems for drug delivery. These biodegradable polymeric nanoparticles enhance properties such as bioavailability and stability, and provide controlled release of bioactive compounds. This review evaluates the classification, synthesis, degradation mechanisms, and biological applications of the biodegradable polymers currently being studied as drug delivery carriers. In addition, the use of nanosystems to solve current drug delivery problems are reviewed. PMID:23990720

  7. Critical evaluation of biodegradable polymers used in nanodrugs.

    Science.gov (United States)

    Marin, Edgar; Briceño, Maria Isabel; Caballero-George, Catherina

    2013-01-01

    Use of biodegradable polymers for biomedical applications has increased in recent decades due to their biocompatibility, biodegradability, flexibility, and minimal side effects. Applications of these materials include creation of skin, blood vessels, cartilage scaffolds, and nanosystems for drug delivery. These biodegradable polymeric nanoparticles enhance properties such as bioavailability and stability, and provide controlled release of bioactive compounds. This review evaluates the classification, synthesis, degradation mechanisms, and biological applications of the biodegradable polymers currently being studied as drug delivery carriers. In addition, the use of nanosystems to solve current drug delivery problems are reviewed.

  8. Polyester-Based, Biodegradable Core-Multishell Nanocarriers for the Transport of Hydrophobic Drugs

    Directory of Open Access Journals (Sweden)

    Karolina A. Walker

    2016-05-01

    Full Text Available A water-soluble, core-multishell (CMS nanocarrier based on a new hyperbranched polyester core building block was synthesized and characterized towards drug transport and degradation of the nanocarrier. The hydrophobic drug dexamethasone was encapsulated and the enzyme-mediated biodegradability was investigated by NMR spectroscopy. The new CMS nanocarrier can transport one molecule of dexamethasone and degrades within five days at a skin temperature of 32 °C to biocompatible fragments.

  9. Chitosan Based Polyelectrolyte Complexes as Potential Carrier Materials in Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Josias H. Hamman

    2010-04-01

    Full Text Available Chitosan has been the subject of interest for its use as a polymeric drug carrier material in dosage form design due to its appealing properties such as biocompatibility, biodegradability, low toxicity and relatively low production cost from abundant natural sources. However, one drawback of using this natural polysaccharide in modified release dosage forms for oral administration is its fast dissolution rate in the stomach. Since chitosan is positively charged at low pH values (below its pKa value, it spontaneously associates with negatively charged polyions in solution to form polyelectrolyte complexes. These chitosan based polyelectrolyte complexes exhibit favourable physicochemical properties with preservation of chitosan’s biocompatible characteristics. These complexes are therefore good candidate excipient materials for the design of different types of dosage forms. It is the aim of this review to describe complexation of chitosan with selected natural and synthetic polyanions and to indicate some of the factors that influence the formation and stability of these polyelectrolyte complexes. Furthermore, recent investigations into the use of these complexes as excipients in drug delivery systems such as nano- and microparticles, beads, fibers, sponges and matrix type tablets are briefly described.

  10. Drug release characterization and preparation of Ca-Alginate microparticle drug carrier using membrane emulsification method

    Energy Technology Data Exchange (ETDEWEB)

    You, Jin Oh; Park, Seong Bae; Park, Ham Yong; Haam, Seung Joo; Kim, Jung Hyun; Kim, Woo Sik [Dept. of Chemical Engineering, Yonsei University, Seoul (Korea)

    1999-10-01

    Conventional alginate bead has been limited to be used as a drug carrier because of its large size. To overcome the disadvantages of conventional large-size alginate drug beads, Ca-alginate microparticles were prepared using membrane emulsification method controlled with the sodium alginate concentration and the pressure of reactor. The optimal monodispersed microparticles were obtained with the concentration of 2 wt % alginate solution and the pressure of 0.4*10{sup 5} Pa. The mean size of our prepared microparticles was about 4 {gamma}m. As the drug solutions, lidocaine{center_dot}HCI(cationic), sodium salicylate(anionic) and 4-acetamidophenol(nonionic) were selected. These three different drugs were loaded in the drug carrier of prepared alginate microparticles. Drug releases were performed in the sodium phosphate buffers of pH 2 and pH 7 and ionic strength of 0.2. The release behavior with the variation of drug charge shoed that of the cationic drug release was retarded more than anionic one due to the ionic interaction between carboxyl group of alginates and positive charge of cationic drug. >From the comparison experiments of the buffers of pH 2 and pH 7, the release was much retarded at pH 2 buffer due to the ionic repulsive force or ionic attractive force between the carboxyl group and the hydroxy or sodium ion in the buffer. Conclusively, the usage of small-size pH sensitive microparticle as a drug carrier has a high potential for the application of drug delivery systems. 19 refs., 9 figs.

  11. NEOGLYCOPROTEINS AS CARRIERS FOR ANTIVIRAL DRUGS - SYNTHESIS AND ANALYSIS OF PROTEIN DRUG CONJUGATES

    NARCIS (Netherlands)

    Molema, Grietje; Jansen, Robert W.; Visser, Jan; Herdewijn, Piet; Moolenaar, Frits; Meijer, Dirk K.F.

    In order to investigate whether neoglycoproteins can potentially act as carriers for targeting of antiviral drugs to certain cell types in the body, various neoglycoproteins were synthesized using thiophosgene-activated p-aminophenyl sugar derivatives. These neoglycoproteins were conjugated with the

  12. Generalized plasma skimming model for cells and drug carriers in the microvasculature.

    Science.gov (United States)

    Lee, Tae-Rin; Yoo, Sung Sic; Yang, Jiho

    2017-04-01

    In microvascular transport, where both blood and drug carriers are involved, plasma skimming has a key role on changing hematocrit level and drug carrier concentration in capillary beds after continuous vessel bifurcation in the microvasculature. While there have been numerous studies on modeling the plasma skimming of blood, previous works lacked in consideration of its interaction with drug carriers. In this paper, a generalized plasma skimming model is suggested to predict the redistributions of both the cells and drug carriers at each bifurcation. In order to examine its applicability, this new model was applied on a single bifurcation system to predict the redistribution of red blood cells and drug carriers. Furthermore, this model was tested at microvascular network level under different plasma skimming conditions for predicting the concentration of drug carriers. Based on these results, the applicability of this generalized plasma skimming model is fully discussed and future works along with the model's limitations are summarized.

  13. Star Polymer-Drug Conjugates with pH-Controlled Drug Release and Carrier Degradation

    Directory of Open Access Journals (Sweden)

    H. Kostková

    2017-01-01

    Full Text Available In this study, we describe the design, synthesis, and physicochemical and preliminary biological characteristics of new biodegradable, high-molecular-weight (HMW drug delivery systems with star-like architectures bearing the cytotoxic drug doxorubicin (DOX attached by a hydrazone bond-containing spacer. The star polymers were synthesized by grafting semitelechelic N-(2-hydroxypropyl methacrylamide (HPMA copolymers on a 2,2-bis(hydroxymethylpropionic acid- (bis-MPA- based polyester dendritic core. The molecular weight of the star polymers ranged from 280 to 450 000 g/mol and could be adjusted by proper selection of the bis-MPA dendrimer generation and by considering the polymer to dendrimer molar ratio. The biodegradation of the polymer conjugates is based on the spontaneous slow hydrolysis of the dendritic core in neutral physiological conditions. Hydrazone spacers in the conjugates were fairly stable at neutral pH (7.4 mimicking blood stream conditions, and DOX was released from the conjugates under mild acidic conditions simulating the tumor cell microenvironment in endosomes and lysosomes (pH 5. Finally, we have shown the significant in vitro cytotoxicity of the star polymer-DOX conjugate on selected cancer cell lines with IC50 values almost comparable with that of the free drug and higher than that observed for a linear polymer-DOX conjugate with much lower molecular weight.

  14. Carrier-Based Drug Delivery System for Treatment of Acne

    Science.gov (United States)

    Vyas, Amber; Kumar Sonker, Avinesh

    2014-01-01

    Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system. PMID:24688376

  15. Applicability of electrospun polypropylene carbonate polymers as a drug carrier for sirolimus.

    Science.gov (United States)

    Sun, Hourong; Gu, Xinghua; Liu, Kai; Fang, Changcun; Tang, Mengmeng

    2017-06-01

    Polypropylene carbonate (PPC), a biodegradable aliphatic polyester, exhibits one particular advantage over other polyesters, which is that following degradation in vivo, it primarily produces H2O and CO2, causing minimal side effects. Although PPC exhibits limited mechanical strength, and is therefore not able to serve as a scaffold to support tissue regeneration, it may be suitable for drug delivery; however, this requires further investigation. In the present study, electrospinning was applied to generate PPC polymers containing sirolimus, a cell growth‑inhibiting drug which is used to treat restenosis. The properties of PPC‑sirolimus polymers were examined using scanning electron microscopy, differential scanning calorimetry and in vitro degradation assays. Drug loading and entrapment efficiency were determined, and in vitro sirolimus‑release from the polymer was assessed. Furthermore, the effect of PPC‑sirolimus polymers on cell growth was measured using an MTT assay in vitro. The results of the present study demonstrated that electrospun PPC polymers formed a uniform three‑dimensional, grid‑intertwined, net‑like structure; the surface of the polymers was smooth and the diameter was ~3 µm. Differential scanning calorimetry analysis demonstrated that sirolimus existed in an amorphous state in the polymer. Following soaking in PBS for 4 weeks, the polymer swelled and the net‑like structure broke down and fragmented. Sirolimus loading and entrapment efficiency were 10.3±3.2 and 95.1±10.6%, respectively. Sirolimus‑release from PPC‑sirolimus polymers continued for 28 days in PBS. PPC‑sirolimus markedly inhibited the growth of rat aortic adventitial fibroblast cells, an effect which was not observed with PPC alone. The results of the present study suggest that PPC polymers are a promising alternative drug carrier for sirolimus.

  16. Polymer/hemoglobin assemblies: biodegradable oxygen carriers for artificial red blood cells.

    Science.gov (United States)

    Li, Taihang; Jing, Xiabin; Huang, Yubin

    2011-07-07

    In routine clinical procedures, blood transfusion is now suffering from the defects of the blood products, like cross-matching, short storage time and virus infection. Various blood substitutes have been designed by researchers through continual efforts. With recent progress in nanotechnology, new types of artificial red blood cells with cellular structure are available. This article aims to describe some artificial red blood cells which encapsulate or conjugate hemoglobin molecules through various approaches, especially the nanoscale self-assembly technique, to mitigate the adverse effects of free hemoglobin molecules. These types of artificial red blood cell systems, which make use of biodegradable polymers as matrix materials, show advantages over the traditional types. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Drug loaded biodegradable polymer microneedles fabricated by hot embossing

    DEFF Research Database (Denmark)

    Andersen, Thor Emil; Andersen, Alina Joukainen; Petersen, Ritika Singh

    2018-01-01

    and had a length of 270 ± 5 μm and a diameter of 84 ± 3 μm. The MNs had sufficient mechanical strength to penetrate the surface of a 10 w/w% gelatine gel without deformation. Finally, PCL MNs containing 20 w/w% of furosemide were fabricated and drug release by diffusion was demonstrated....

  18. Novel "soft" biodegradable nanoparticles prepared from aliphatic based monomers as a potential drug delivery system

    Czech Academy of Sciences Publication Activity Database

    Jäger, Alessandro; Gromadzki, Daniel; Jäger, Eliezer; Giacomelli, F. C.; Kozlowska, A.; Kobera, Libor; Brus, Jiří; Říhová, Blanka; El Fray, M.; Ulbrich, Karel; Štěpánek, Petr

    2012-01-01

    Roč. 8, č. 16 (2012), s. 4343-4354 ISSN 1744-683X R&D Projects: GA AV ČR IAAX00500803; GA ČR GAP208/10/1600 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510 Keywords : biodegradable nanoparticles * light scattering from polymer nanoparticles * drug release Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.909, year: 2012

  19. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine

    Directory of Open Access Journals (Sweden)

    Hong X

    2013-09-01

    Full Text Available Xiaoyun Hong,1,2,* Liangming Wei,3,* Fei Wu,2,* Zaozhan Wu,2 Lizhu Chen,2 Zhenguo Liu,1 Weien Yuan2 1Department of Neurology, Xinhua Hospital, Shanghai, People's Republic of China; 2School of Pharmacy, Shanghai JiaoTong University, Shanghai, People's Republic of China; 3Research Institute of Micro/Nano Science and Technology, Shanghai JiaoTong University, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation. Keywords: microneedle, dissolving, biodegradable, sustained release

  20. Drug loaded biodegradable load-bearing nanocomposites for damaged bone repair

    Science.gov (United States)

    Gutmanas, E. Y.; Gotman, I.; Sharipova, A.; Psakhie, S. G.; Swain, S. K.; Unger, R.

    2017-09-01

    In this paper we present a short review-scientific report on processing and properties, including in vitro degradation, of load bearing biodegradable nanocomposites as well as of macroporous 3D scaffolds for bone ingrowth. Biodegradable implantable devices should slowly degrade over time and disappear with ingrown of natural bone replacing the synthetic graft. Compared to low strength biodegradable polymers, and brittle CaP ceramics, biodegradable CaP-polymer and CaP-metal nanocomposites, mimicking structure of natural bone, as well as strong and ductile metal nanocomposites can provide to implantable devices both strengths and toughness. Nanostructuring of biodegradable β-TCP (tricalcium phosphate)-polymer (PCL and PLA), β-TCP-metal (FeMg and FeAg) and of Fe-Ag composites was achieved employing high energy attrition milling of powder blends. Nanocomposite powders were consolidated to densities close to theoretical by high pressure consolidation at ambient temperature—cold sintering, with retention of nanoscale structure. The strength of developed nanocomposites was significantly higher as compared with microscale composites of the same or similar composition. Heat treatment at moderate temperatures in hydrogen flow resulted in retention of nanoscale structure and higher ductility. Degradation of developed biodegradable β-TCP-polymer, β-TCP-metal and of Fe-Ag nanocomposites was studied in physiological solutions. Immersion tests in Ringer's and saline solution for 4 weeks resulted in 4 to 10% weight loss and less than 50% decrease in compression or bending strength, the remaining strength being significantly higher than the values reported for other biodegradable materials. Nanostructuring of Fe-Ag based materials resulted also in an increase of degradation rate because of creation on galvanic Fe-Ag nanocouples. In cell culture experiments, the developed nanocomposites supported the attachment the human osteoblast cells and exhibited no signs of cytotoxicity

  1. Synthesis, characterization, drug release and transdentinal delivery studies of magnetic nanocubes coated with biodegradable poly(2-(dimethyl amino)ethyl methacrylate)

    Science.gov (United States)

    Ajkidkarn, Phranot; Ritprajak, Patcharee; Injumpa, Wishulada; Porntaveetus, Thantrira; Insin, Numpon

    2017-04-01

    Nanotechnology on magnetism and magnetic materials has been developed and studied extensively for the recent decades. Magnetic nanoparticles were applied in magnetic targeting, magnetic drug carriers, and diagnostic materials. In this work, the development of magnetic nanocomposites and their applications as drug carriers for dentistry were investigated. Well-defined ferromagnetic magnetite nanocubes (FMNCs) with the diameter of around 60 nm were synthesized using a thermal decomposition method at 290 °C with iron-oleate complexes as starting materials resulting in nanostructure with high saturation magnetization. The FMNCs were then coated with poly(2-(dimethyl amino)ethyl methacrylate) (PDMAEMA), a water-soluble, biodegradable, and pH-responsive polymer, in order to become good drug carriers with excellent dispersity in biological buffer, low cytotoxicity, and controllable drug release. The polymer coating was performed using atom transfer radical polymerization (ATRP). By using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, FMNCs/PDMAEMA showed the high compatibility in fibroblast and macrophage cell line with the cell viability of more than 80% after incubation with the highest nanocomposites concentration of 100 μg/mL for 24 h. Furthermore, the FMNCs/PDMAEMA subsequently demonstrated the anti-inflammatory effect on macrophages by suppression of pro-inflammatory cytokines, IL-6 and TNF-α production in a dose-dependent manner. The behavior of model drug alkaline hyperchlorite released from the FMNCs/PDMAEMA indicated that the drug release could be controlled by altering pH of the environment. As a result of successfully synthesized FMCNs/PDMAEMA, dentine infiltration of FMNCs/PDMAEMA was performed. It was observed that FMNCs/PDMAEMA could significantly infiltrate the dentine within 30 min under an external magnetic field. Our findings indicated the therapeutic potential of the FMNCs/PDMAEMA as transdentinal drug carriers with its

  2. Effect of drug-carrier interaction on the dissolution behavior of solid dispersion tablets

    NARCIS (Netherlands)

    Srinarong, Parinda; Kouwen, Sander; Visser, Marinella R; Hinrichs, Wouter L J; Frijlink, Henderik W

    2010-01-01

    The objective of this study was to compare the dissolution behavior of tablets prepared from solid dispersions with and without drug-carrier interactions. Diazepam and nifedipine were used as model drugs. Two types of carriers were used; polyvinylpyrrolidone (PVP K12, K30 and K60) and saccharides

  3. Stretch-induced biodegradation of polyelectrolyte multilayer films for drug release.

    Science.gov (United States)

    Barthes, Julien; Mertz, Damien; Bach, Charlotte; Metz-Boutigue, Marie-Hélène; Senger, Bernard; Voegel, Jean-Claude; Schaaf, Pierre; Lavalle, Philippe

    2012-09-25

    The design of stimuli-responsive polymer assemblies for the controlled release of bioactive molecules has raised considerable interest these two last decades. Herein, we report the design of mechanically responsive drug-releasing films made of polyelectrolyte multilayers. A layer-by-layer (LbL) reservoir containing biodegradable polyelectrolytes is capped with a mechanosensitive LbL barrier and responds to stretching by a total enzymatic degradation of the film. This strategy is successfully applied for the release in solution of an anticancer drug initially loaded within the architecture.

  4. Spatially discrete thermal drawing of biodegradable microneedles for vascular drug delivery.

    Science.gov (United States)

    Choi, Chang Kuk; Lee, Kang Ju; Youn, Young Nam; Jang, Eui Hwa; Kim, Woong; Min, Byung-Kwon; Ryu, WonHyoung

    2013-02-01

    Spatially discrete thermal drawing is introduced as a novel method for the fabrication of biodegradable microneedles with ultra-sharp tip ends. This method provides the enhanced control of microneedle shapes by spatially controlling the temperature of drawn polymer as well as drawing steps and speeds. Particular focus is given on the formation of sharp tip ends of microneedles at the end of thermal drawing. Previous works relied on the fracture of polymer neck by fast drawing that often causes uncontrolled shapes of microneedle tips. Instead, this approach utilizes the surface energy of heated polymer to form ultra-sharp tip ends. We have investigated the effect of such temperature control, drawing speed, and drawing steps in thermal drawing process on the final shape of microneedles using biodegradable polymers. XRD analysis was performed to analyze the effect of thermal cycle on the biodegradable polymer. Load-displacement measurement also showed the dependency of mechanical strengths of microneedles on the microneedle shapes. Ex vivo vascular tissue insertion and drug delivery demonstrated microneedle insertion to tunica media layer of canine aorta and drug distribution in the tissue layer. Copyright © 2012 Elsevier B.V. All rights reserved.

  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. Size-controlled synthesis of biodegradable nanocarriers for targeted ...

    Indian Academy of Sciences (India)

    Abstract. Research for synthesis of size-controlled carriers is currently challenging one. In this research paper, a method for size-controlled synthesis of biodegradable nanocarriers is proposed and described. Salting out method is suitable for both hydrophilic and hydrophobic drugs for the encapsulation on carriers.

  7. Size-controlled synthesis of biodegradable nanocarriers for targeted ...

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Research for synthesis of size-controlled carriers is currently challenging one. In this research paper, a method for size-controlled synthesis of biodegradable nanocarriers is proposed and described. Salting out method is suitable for both hydrophilic and hydrophobic drugs for the encapsulation on carriers.

  8. Erythrocytes as Carriers for Drugs and Contrast Agents

    Directory of Open Access Journals (Sweden)

    Mauro Magnani

    2014-01-01

    Full Text Available Erythrocytes, also known as Red Blood Cells (RBC, are typically used in transfusion medicine to replace lost blood in patients who underwent different kinds of medical treatments as well as those involved in accidents resulting in blood loss. In addition to these common uses, RBC are being used for a variety of new applications either as therapeutics or as diagnostics. Most of these novel approaches are made possible due to the peculiar properties of these cells. We have invented a technology that allows cells to be opened and resealed without affecting their main physiological characteristics with a minimal amount of patient blood.  Uses of processed RBCs in biomedical engineering include work with drugs, biomedical compounds and/or nanomaterials. These constructs are a new armamentarium available to the physicians for the release of drugs in circulation, for targeting drugs to selected sites in the body, or for in vivo diagnostic procedures based on magnetic and/or optical methods. Autologous human RBC loaded with dexamethasone (EryDex, a common corticosteroid,  have been used in the treatment of Cystic Fibrosis, Crohn’s Disease, and other severe inflammatory conditions. Benefits and safety of this technology have been documented in over 2,500 treatments. EryDel SpA is a company focused on developing and commercializing innovative therapies and diagnostics based on the use of autologous RBCs as agent carriers. More recently, EryDel SpA completed a Phase II Proof of Concept study in patients with Ataxia Telangiectasia (AT, a rare progressive neurological autosomal recessive disorder that leads to mortality in most patients at an early age, with significant benefit seen on primary and secondary end-points. EryDex treatment has received Orphan Drug Designation by EMA for the treatment of Cystic Fibrosis and both by EMA and FDA for the treatment of AT. The encapsulation of superparamagnetic nanoparticles within RBC has lead to the generation

  9. Pickering emulsions stabilized by biodegradable block copolymer micelles for controlled topical drug delivery.

    Science.gov (United States)

    Laredj-Bourezg, Faiza; Bolzinger, Marie-Alexandrine; Pelletier, Jocelyne; Chevalier, Yves

    2017-10-05

    Surfactant-free biocompatible and biodegradable Pickering emulsions were investigated as vehicles for skin delivery of hydrophobic drugs. O/w emulsions of medium-chain triglyceride (MCT) oil droplets loaded with all-trans retinol as a model hydrophobic drug were stabilized by block copolymer nanoparticles: either poly(lactide)-block-poly(ethylene glycol) (PLA-b-PEG) or poly(caprolactone)-block-poly(ethylene glycol) (PCL-b-PEG). Those innovative emulsions were prepared using two different processes allowing drug loading either inside oil droplets or inside both oil droplets and non-adsorbed block copolymer nanoparticles. Skin absorption of retinol was investigated in vitro on pig skin biopsies using the Franz cell method. Supplementary experiments by confocal fluorescence microscopy allowed the visualization of skin absorption of the Nile Red dye on histological sections. Retinol and Nile Red absorption experiments showed the large accumulation of hydrophobic drugs in the stratum corneum for the Pickering emulsions compared to the surfactant-based emulsion and an oil solution. Loading drug inside both oil droplets and block copolymer nanoparticles enhanced again skin absorption of drugs, which was ascribed to the supplementary contribution of free block copolymer nanoparticles loaded with drug. Such effect allowed tuning drug delivery to skin over a wide range by means of a suitable selection of either the formulation or the drug loading process. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    Locatelli, Erica; Comes Franchini, Mauro

    2012-01-01

    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.

  11. Synergic Adsorption–Biodegradation by an Advanced Carrier for Enhanced Removal of High-Strength Nitrogen and Refractory Organics

    KAUST Repository

    Ahmad, Muhammad

    2017-03-29

    Coking wastewater contains not only high-strength nitrogen but also toxic biorefractory organics. This study presents simultaneous removal of high-strength quinoline, carbon, and ammonium in coking wastewater by immobilized bacterial communities composed of a heterotrophic strain Pseudomonas sp. QG6 (hereafter referred as QG6), ammonia-oxidizing bacteria (AOB), and anaerobic ammonium oxidation bacteria (anammox). The bacterial immobilization was implemented with the help of a self-designed porous cubic carrier that created structured microenvironments including an inner layer adapted for anaerobic bacteria, a middle layer suitable for coaggregation of certain aerobic and anaerobic bacteria, and an outer layer for heterotrophic bacteria. By coating functional polyurethane foam (FPUF) with iron oxide nanoparticles (IONPs), the biocarrier (IONPs-FPUF) could provide a good outer-layer barrier for absorption and selective treatment of aromatic compounds by QG6, offer a conducive environment for anammox in the inner layer, and provide a mutualistic environment for AOB in the middle layer. Consequently, simultaneous nitrification and denitrification were reached with the significant removal of up to 322 mg L (98%) NH, 311 mg L (99%) NO, and 633 mg L (97%) total nitrogen (8 mg L averaged NO concentration was recorded in the effluent), accompanied by an efficient removal of chemical oxygen demand by 3286 mg L (98%) and 350 mg L (100%) quinoline. This study provides an alternative way to promote synergic adsorption and biodegradation with the help of a modified biocarrier that has great potential for treatment of wastewater containing high-strength carbon, toxic organic pollutants, and nitrogen.

  12. Biodegradable Peptide-Silica Nanodonuts.

    Science.gov (United States)

    Maggini, Laura; Travaglini, Leana; Cabrera, Ingrid; Castro-Hartmann, Pablo; De Cola, Luisa

    2016-03-07

    We report hybrid organosilica toroidal particles containing a short peptide sequence as the organic component of the hybrid systems. Once internalised in cancer cells, the presence of the peptide allows for interaction with peptidase enzymes, which attack the nanocarrier effectively triggering its structural breakdown. Moreover, these biodegradable nanovectors are characterised by high cellular uptake and exocytosis, showing great potential as biodegradable drug carriers. To demonstrate this feature, doxorubicin was employed and its delivery in HeLa cells investigated. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Novel 'nano in nano' composites for sustained drug delivery: biodegradable nanoparticles encapsulated into nanofiber non-wovens.

    Science.gov (United States)

    Beck-Broichsitter, Moritz; Thieme, Marcel; Nguyen, Juliane; Schmehl, Thomas; Gessler, Tobias; Seeger, Werner; Agarwal, Seema; Greiner, Andreas; Kissel, Thomas

    2010-12-08

    Novel 'nano in nano' composites consisting of biodegradable polymer nanoparticles incorporated into polymer nanofibers may efficiently modulate drug delivery. This is shown here using a combination of model compound-loaded biodegradable nanoparticles encapsulated in electrospun fibers. The dye coumarin 6 is used as model compound for a drug in order to simulate drug release from loaded poly(lactide-co-glycolide) nanoparticles. Dye release from the nanoparticles occurs immediately in aqueous solution. Dye-loaded nanoparticles which are encapsulated by electrospun polymer nanofibers display a significantly retarded release. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Versatile Chemical Derivatizations to Design Glycol Chitosan-Based Drug Carriers

    Directory of Open Access Journals (Sweden)

    Sung Eun Kim

    2017-10-01

    Full Text Available Glycol chitosan (GC and its derivatives have been extensively investigated as safe and effective drug delivery carriers because of their unique physiochemical and biological properties. The reactive functional groups such as the amine and hydroxyl groups on the GC backbone allow for easy chemical modification with various chemical compounds (e.g., hydrophobic molecules, crosslinkers, and acid-sensitive and labile molecules, and the versatility in chemical modifications enables production of a wide range of GC-based drug carriers. This review summarizes the versatile chemical modification methods that can be used to design GC-based drug carriers and describes their recent applications in disease therapy.

  15. Urethral in situ biocompatibility of new drug-eluting biodegradable stents: an experimental study in the rabbit.

    Science.gov (United States)

    Kotsar, Andres; Isotalo, Taina; Uurto, Ilkka; Mikkonen, Joonas; Martikainen, Paula; Talja, Martti; Kellomäki, Minna; Salenius, Juha-Pekka; Tammela, Teuvo L J

    2009-04-01

    To assess the effect of drug-eluting properties on the degradation process and the biocompatibility of biodegradable drug-eluting urethral stents. Braided biodegradable 80 L/20D-PLGA (copolymer of polylactide and polyglycolide) stents with drug-eluting properties were used as the test material. The drugs analysed were indomethacin, dexamethasone and ciprofloxacine. 80 L/20D-PLGA stents without a drug coating served as controls. In all, 16 male rabbits were used and divided into four groups. The stents were inserted under general anaesthesia into the posterior urethra. After 1 month, the rabbits were killed and the urethra removed for histological and optic microscopy analyses. Control stents and the dexamethasone-eluting stents degraded totally during the follow-up period. Conversely, in both indomethacin- and ciprofloxacine-eluting stent groups, the degradation process was significantly delayed and they induced an increase in epithelial hyperplasia. Histological analysis showed that all the stents induced eosinophilia, but there were no significant differences in the intensity of acute or chronic inflammatory reactions and fibrosis. A drug-eluting capacity can be added to biodegradable stents. The addition of a drug influences the biodegradation time of PLGA urethral stents. Further studies are needed, to find the proper concentrations and releasing profiles of the drugs to achieve the desired bioactivity and biocompatibility properties.

  16. Nanoporous materials modified with biodegradable polymers as models for drug delivery applications

    DEFF Research Database (Denmark)

    Gruber, Mathias F; Schulte, Lars; Ndoni, Sokol

    2013-01-01

    Polymers play a central role in the development of carriers for diagnostic and therapeutic agents. Especially the use of either degradable polymers or porous materials to encapsulate drug compounds in order to obtain steady drug release profiles has received much attention. We present here a proof...... of principle for a system combining these two encapsulation methods and consisting of a nanoporous polymer (NP) with the pores filled with a degradable polymer mixed with a drug model. Rhodamine 6G (R6G) mixed with Poly(l-Lactic Acid) (PLLA) were confined within the 14nm pores of a NP with gyroid morphology...

  17. Interfacing materials science and biology for drug carrier design.

    Science.gov (United States)

    Such, Georgina K; Yan, Yan; Johnston, Angus P R; Gunawan, Sylvia T; Caruso, Frank

    2015-04-08

    Over the last ten years, there has been considerable research interest in the development of polymeric carriers for biomedicine. Such delivery systems have the potential to significantly reduce side effects and increase the bioavailability of poorly soluble therapeutics. The design of carriers has relied on harnessing specific variations in biological conditions, such as pH or redox potential, and more recently, by incorporating specific peptide cleavage sites for enzymatic hydrolysis. Although much progress has been made in this field, the specificity of polymeric carriers is still limited when compared with their biological counterparts. To synthesize the next generation of carriers, it is important to consider the biological rationale for materials design. This requires a detailed understanding of the cellular microenvironments and how these can be harnessed for specific applications. In this review, several important physiological cues in the cellular microenvironments are outlined, with a focus on changes in pH, redox potential, and the types of enzymes present in specific regions. Furthermore, recent studies that use such biologically inspired triggers to design polymeric carriers are highlighted, focusing on applications in the field of therapeutic delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. pH-controlled drug loading and release from biodegradable microcapsules

    Science.gov (United States)

    Zhao, Qinghe; Li, Bingyun

    2013-01-01

    Microcapsules made of biopolymers are of both scientific and technological interest and have many potential applications in medicine including their use as controlled drug delivery devices. The present study employs the electrostatic interaction between polycations and polyanions to form a multilayered microcapsule shell and also to control the loading and release of charged drug molecules inside the microcapsule. Micron-sized CaCO3 particles were synthesized and integrated with chondroitin sulfate (CS) through a reaction between Na2CO3 and Ca(NO3)2 solutions suspended with CS macromolecules. Oppositely-charged biopolymers were alternately deposited onto the synthesized particles using electrostatic layer-by-layer self-assembly, and glutaraldehyde was introduced to crosslink the multilayered shell structure. Microcapsules integrated with CS inside the multilayered shells were obtained after decomposition of the CaCO3 templates. The integration of a matrix, i.e. CS, enabled the subsequent selective control of drug loading and release. The CS integrated microcapsules were loaded with a model drug, i.e. bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA), and it was shown that pH was an effective means of controlling the loading and release of FITC-BSA. Such CS integrated microcapsules may be used for controlled localized drug delivery as biodegradable devices, which have advantages in reducing systemic side effects and increasing drug efficacy. PMID:18657478

  19. Design, development and optimization of oral colon targeted drug delivery system of azathioprine using biodegradable polymers.

    Science.gov (United States)

    Nath, Bipul; Nath, L K

    2013-01-01

    The present study was aimed at designing a microflora triggered colon targeted drug delivery system (MCDDS) based on swellable polysaccharide, Sterculia gum in combination with biodegradable polymers with a view to specifically deliver azathioprine in the colonic region for the treatment of IBD with reduced systemic toxicity. The microflora degradation properties of Sterculia gum was investigated in rat caecal phosphate buffer medium. The polysaccharide tablet cores were coated to different film thicknesses with blends of Eudragit RLPO and chitosan and overcoated with Eudragit L00 to provide acid and intestinal resistance. Swelling and drug release studies were carried out in simulated gastric fluid, SGF (pH 1.2), simulated intestinal fluid, SIF (pH 6.8) and simulated colonic fluid, SCF (pH 7.4 under anaerobic environment), respectively. Drug release study in SCF revealed that swelling force of the Sterculia gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora activated environment. The degradation of chitosan was the rate-limiting factor for drug release in the colon. Drug release from the MCDDS was directly proportional to the concentration of the pore former (chitosan), but inversely related to the Eudragit RLPO coating thickness.

  20. Peptide Drug Release Behavior from Biodegradable Temperature-Responsive Injectable Hydrogels Exhibiting Irreversible Gelation

    Directory of Open Access Journals (Sweden)

    Kazuyuki Takata

    2017-10-01

    Full Text Available We investigated the release behavior of glucagon-like peptide-1 (GLP-1 from a biodegradable injectable polymer (IP hydrogel. This hydrogel shows temperature-responsive irreversible gelation due to the covalent bond formation through a thiol-ene reaction. In vitro sustained release of GLP-1 from an irreversible IP formulation (F(P1/D+PA40 was observed compared with a reversible (physical gelation IP formulation (F(P1. Moreover, pharmaceutically active levels of GLP-1 were maintained in blood after subcutaneous injection of the irreversible IP formulation into rats. This system should be useful for the minimally invasive sustained drug release of peptide drugs and other water-soluble bioactive reagents.

  1. Biodegradable polyglycerols with randomly distributed ketal groups as multi-functional drug delivery systems.

    Science.gov (United States)

    Shenoi, Rajesh A; Lai, Benjamin F L; Imran ul-haq, Muhammad; Brooks, Donald E; Kizhakkedathu, Jayachandran N

    2013-08-01

    Biodegradable multi-functional polymeric nanostructures that undergo controlled degradation in response to physiological cues are important in numerous biomedical applications including drug delivery, bio-conjugation and tissue engineering. In this paper, we report the development of a new class of water soluble multi-functional branched biodegradable polymer with high molecular weight and biocompatibility which demonstrates good correlation of in vivo biodegradation and in vitro hydrolysis. Main chain degradable hyperbranched polyglycerols (HPG) (20-100 kDa) were synthesized by the introduction of acid labile groups within the polymer structure by an anionic ring opening copolymerization of glycidol with ketal-containing epoxide monomers with different ketal structures. The water soluble biodegradable HPGs with randomly distributed ketal groups (RBHPGs) showed controlled degradation profiles in vitro depending on the pH of solution, temperature and the structure of incorporated ketal groups, and resulted in non-toxic degradation products. NMR studies demonstrated the branched nature of RBHPGs which is correlating with their smaller hydrodynamic radii. The RBHPGs and their degradation products exhibited excellent blood compatibility and tissue compatibility based on various analyses methods, independent of their molecular weight and ketal group structure. When administered intravenously in mice, tritium labeled RBHPG of molecular weight 100 kDa with dimethyl ketal group showed a circulation half life of 2.7 ± 0.3 h, correlating well with the in vitro polymer degradation half life (4.3 h) and changes in the molecular weight profile during the degradation (as measured by gel permeation chromatography) in buffer conditions at 37 °C. The RBHPG degraded into low molecular weight fragments that were cleared from circulation rapidly. The biodistribution and excretion studies demonstrated that RBHPG exhibited significantly lower tissue accumulation and enhanced urinary

  2. Core–shell composite particles composed of biodegradable polymer particles and magnetic iron oxide nanoparticles for targeted drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Oka, Chiemi; Ushimaru, Kazunori [Department of Innovative and Engineered Materials, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8502 (Japan); Horiishi, Nanao [Bengala Techno Laboratory, 9-5-1006, 1-1 Kodai, Miyamae-ku, Kawasaki 216-0007 (Japan); Tsuge, Takeharu [Department of Innovative and Engineered Materials, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8502 (Japan); Kitamoto, Yoshitaka, E-mail: kitamoto.y.aa@m.titech.ac.jp [Department of Innovative and Engineered Materials, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8502 (Japan)

    2015-05-01

    Core–shell composite particles with biodegradability and superparamagnetic behavior were prepared using a Pickering emulsion for targeted drug delivery based on magnetic guidance. The composite particles were composed of a core of biodegradable polymer and a shell of assembled magnetic iron oxide nanoparticles. It was found that the dispersibility of the nanoparticles is crucial for controlling the core–shell structure. The addition of a small amount of dispersant into the nanoparticle's suspension could improve the dispersibility and led to the formation of composite particles with a thin magnetic shell covering a polymeric core. The composite particles were also fabricated with a model drug loaded into the core, which was released via hydrolysis of the core under strong alkaline conditions. Because the core can also be biodegraded by lipase, this result suggests that the slow release of the drug from the composite particles should occur inside the body. - Highlights: • Core−shell composites with biodegradability and magnetism are prepared. • O/W emulsion stabilized by iron oxide nanoparticles is utilized for the preparation. • The nanoparticle's dispersibility is crucial for controlling the composite structure. • Composites loading a model drug are also prepared. • The model drug is released with decomposition of the composites.

  3. Core–shell composite particles composed of biodegradable polymer particles and magnetic iron oxide nanoparticles for targeted drug delivery

    International Nuclear Information System (INIS)

    Oka, Chiemi; Ushimaru, Kazunori; Horiishi, Nanao; Tsuge, Takeharu; Kitamoto, Yoshitaka

    2015-01-01

    Core–shell composite particles with biodegradability and superparamagnetic behavior were prepared using a Pickering emulsion for targeted drug delivery based on magnetic guidance. The composite particles were composed of a core of biodegradable polymer and a shell of assembled magnetic iron oxide nanoparticles. It was found that the dispersibility of the nanoparticles is crucial for controlling the core–shell structure. The addition of a small amount of dispersant into the nanoparticle's suspension could improve the dispersibility and led to the formation of composite particles with a thin magnetic shell covering a polymeric core. The composite particles were also fabricated with a model drug loaded into the core, which was released via hydrolysis of the core under strong alkaline conditions. Because the core can also be biodegraded by lipase, this result suggests that the slow release of the drug from the composite particles should occur inside the body. - Highlights: • Core−shell composites with biodegradability and magnetism are prepared. • O/W emulsion stabilized by iron oxide nanoparticles is utilized for the preparation. • The nanoparticle's dispersibility is crucial for controlling the composite structure. • Composites loading a model drug are also prepared. • The model drug is released with decomposition of the composites

  4. Polycaprolactone diacrylate crosslinked biodegradable semi-interpenetrating networks of polyacrylamide and gelatin for controlled drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Jaiswal, Maneesh; Koul, Veena [Centre for Biomedical Engineering, Indian Institute of Technology, New Delhi 110016 (India); Dinda, Amit K [Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029 (India); Gupta, Asheesh, E-mail: veenak_iitd@yahoo.co [Department of Biochemical Pharmacology, Defense Institute of Physiology and Allied Sciences, Ministry of Defense, New Delhi 110059 (India)

    2010-12-15

    A biodegradable semi-interpenetrating hydrogel network (semi-IPN) of polyacrylamide and gelatin was prepared using polycaprolactone diacrylate (mol. wt {approx} 640) as a crosslinker. The drug-polymer interaction and IPN formation were investigated by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) and thermal gravimetric analysis (TGA). Scanning electron micrographs of lyophilized matrices revealed porous internal structure with varying pore sizes under equilibrium hydrated conditions, depending upon formulation composition. pH-dependent swelling and degradation was enhanced with increasing gelatin content and decreasing crosslinker concentration (Cs). Compression modulus (CM) (at 20% strain) increased significantly from 23 {+-} 1.4 to 75 {+-} 2.7 kPa (p < 0.02) with increasing Cs (from 0.5 to 2.0 mol%), while it decreased from 162 {+-} 6.4 to 23 {+-} 1.4 kPa (p < 0.05) with decreasing PAm/G ratio. Cell viability studies by MTT assay showed excellent cytocompatibility of matrices with fibroblast L929 cells. Curcumin, a hydrophobic phytochemical, was loaded by a diffusion method and its release profile was investigated in 4% w/v aqueous BSA solution at 75 rpm (at 37 {+-} 0.2 {sup 0}C). Fitting of drug release data in the Korsmeyer-Peppas model suggested sustained release behavior up to 10 days with a combination of diffusion and erosion mechanism (0.5 < n < 1.0; M{sub t}/M{sub {infinity} {<=}} 0.6). The newly developed porous, biodegradable and elastic semi-IPNs may serve as an ideal matrix for controlled drug release and wound healing applications. The possibilities can be explored for pharmaceutical and tissue engineering applications.

  5. In vivo imaging of passively tumor targeted polymer carrier and the enzymatically cleavable drug model

    Czech Academy of Sciences Publication Activity Database

    Pola, Robert; Heinrich, A. K.; Mueller, T.; Kostka, Libor; Mäder, K.; Pechar, Michal; Etrych, Tomáš

    2017-01-01

    Roč. 6, 4 (Suppl) (2017), s. 90 ISSN 2325-9604. [International Conference and Exhibition on Nanomedicine and Drug Delivery. 29.05.2017-31.05.2017, Osaka] R&D Projects: GA MZd(CZ) NV16-28594A Institutional support: RVO:61389013 Keywords : polymer drug carrier * tumor targeting * enzymatic release Subject RIV: FD - Oncology ; Hematology

  6. Synthesis, characterization, drug release and transdentinal delivery studies of magnetic nanocubes coated with biodegradable poly(2-(dimethyl amino)ethyl methacrylate)

    Energy Technology Data Exchange (ETDEWEB)

    Ajkidkarn, Phranot [Petrochemistry and Polymer Science Program, Faculty of Science, Chulalongkorn University, Bangkok 10330 (Thailand); Ritprajak, Patcharee [Department of Microbiology and RU in Oral Microbiology and Immunology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330 (Thailand); Injumpa, Wishulada [Departmen of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330 (Thailand); Porntaveetus, Thantrira [Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330 (Thailand); STAR on Craniofacial and Skeletal Disorders, Chulalongkorn University, Bangkok 10330 (Thailand); Insin, Numpon, E-mail: Numpon.I@chula.ac.th [Departmen of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330 (Thailand)

    2017-04-01

    Nanotechnology on magnetism and magnetic materials has been developed and studied extensively for the recent decades. Magnetic nanoparticles were applied in magnetic targeting, magnetic drug carriers, and diagnostic materials. In this work, the development of magnetic nanocomposites and their applications as drug carriers for dentistry were investigated. Well-defined ferromagnetic magnetite nanocubes (FMNCs) with the diameter of around 60 nm were synthesized using a thermal decomposition method at 290 °C with iron-oleate complexes as starting materials resulting in nanostructure with high saturation magnetization. The FMNCs were then coated with poly(2-(dimethyl amino)ethyl methacrylate) (PDMAEMA), a water-soluble, biodegradable, and pH-responsive polymer, in order to become good drug carriers with excellent dispersity in biological buffer, low cytotoxicity, and controllable drug release. The polymer coating was performed using atom transfer radical polymerization (ATRP). By using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, FMNCs/PDMAEMA showed the high compatibility in fibroblast and macrophage cell line with the cell viability of more than 80% after incubation with the highest nanocomposites concentration of 100 μg/mL for 24 h. Furthermore, the FMNCs/PDMAEMA subsequently demonstrated the anti-inflammatory effect on macrophages by suppression of pro-inflammatory cytokines, IL-6 and TNF-α production in a dose-dependent manner. The behavior of model drug alkaline hyperchlorite released from the FMNCs/PDMAEMA indicated that the drug release could be controlled by altering pH of the environment. As a result of successfully synthesized FMCNs/PDMAEMA, dentine infiltration of FMNCs/PDMAEMA was performed. It was observed that FMNCs/PDMAEMA could significantly infiltrate the dentine within 30 min under an external magnetic field. Our findings indicated the therapeutic potential of the FMNCs/PDMAEMA as transdentinal drug carriers with its

  7. Dissolution Enhancement of Drugs. Part II: Effect of Carriers ...

    African Journals Online (AJOL)

    Recent high throughput screening and combinatorial and parallel synthesis are increasing the number of drug molecules which are highly lipophilic. The oral route is the most preferred route of drug administration due to its convenience, good patient compliance and low medicine production costs. The challenges to ...

  8. pH-triggered drug release from biodegradable microwells for oral drug delivery

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Nagstrup, Johan; Gordon, Sarah

    2015-01-01

    Microwells fabricated from poly-L-lactic acid (PLLA) were evaluated for their application as an oral drug delivery system using the amorphous sodium salt of furosemide (ASSF) as a model drug. Hot embossing of PLLA resulted in fabrication of microwells with an inner diameter of 240 μm and a height...... of microwell cavities with an Eudragit® layer prevented drug release in biorelevant gastric medium. An immediate release of the ASSF from coated microwells was observed in the intestinal medium. This pH-triggered release behavior demonstrates the future potential of PLLA microwells as a site-specific oral drug...

  9. The non-steroidal anti-inflammatory drug diclofenac is readily biodegradable in agricultural soils

    Energy Technology Data Exchange (ETDEWEB)

    Al-Rajab, Abdul Jabbar; Sabourin, Lyne [Agriculture and Agri-Food Canada, London, ON, Canada N5V 4T3 (Canada); Lapen, David R. [Agriculture and Agri-Food Canada, Ottawa ON, Canada K1A 0C6 (Canada); Topp, Edward, E-mail: ed.topp@agr.gc.ca [Agriculture and Agri-Food Canada, London, ON, Canada N5V 4T3 (Canada)

    2010-12-01

    Diclofenac, 2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetic acid, is an important non-steroidal anti-inflammatory drug widely used for human and animals to reduce inflammation and pain. Diclofenac could potentially reach agricultural lands through the application of municipal biosolids or wastewater, and in the absence of any environmental fate data, we evaluated its persistence in agricultural soils incubated in the laboratory. {sup 14}C-Diclofenac was rapidly mineralized without a lag when added to soils varying widely in texture (sandy loam, loam, clay loam). Over a range of temperature and moisture conditions extractable {sup 14}C-diclofenac residues decreased with half lives < 5 days. No extractable transformation products were detectable by HPLC. Diclofenac mineralization in the loam soil was abolished by heat sterilization. Addition of biosolids to sterile or non-sterile soil did not accelerate the dissipation of diclofenac. These findings indicate that diclofenac is readily biodegradable in agricultural soils.

  10. The non-steroidal anti-inflammatory drug diclofenac is readily biodegradable in agricultural soils

    International Nuclear Information System (INIS)

    Al-Rajab, Abdul Jabbar; Sabourin, Lyne; Lapen, David R.; Topp, Edward

    2010-01-01

    Diclofenac, 2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetic acid, is an important non-steroidal anti-inflammatory drug widely used for human and animals to reduce inflammation and pain. Diclofenac could potentially reach agricultural lands through the application of municipal biosolids or wastewater, and in the absence of any environmental fate data, we evaluated its persistence in agricultural soils incubated in the laboratory. 14 C-Diclofenac was rapidly mineralized without a lag when added to soils varying widely in texture (sandy loam, loam, clay loam). Over a range of temperature and moisture conditions extractable 14 C-diclofenac residues decreased with half lives < 5 days. No extractable transformation products were detectable by HPLC. Diclofenac mineralization in the loam soil was abolished by heat sterilization. Addition of biosolids to sterile or non-sterile soil did not accelerate the dissipation of diclofenac. These findings indicate that diclofenac is readily biodegradable in agricultural soils.

  11. Nanoporous materials modified with biodegradable polymers as models for drug delivery applications

    DEFF Research Database (Denmark)

    Gruber, Mathias F; Schulte, Lars; Ndoni, Sokol

    2013-01-01

    Polymers play a central role in the development of carriers for diagnostic and therapeutic agents. Especially the use of either degradable polymers or porous materials to encapsulate drug compounds in order to obtain steady drug release profiles has received much attention. We present here a proof...... of principle for a system combining these two encapsulation methods and consisting of a nanoporous polymer (NP) with the pores filled with a degradable polymer mixed with a drug model. Rhodamine 6G (R6G) mixed with Poly(l-Lactic Acid) (PLLA) were confined within the 14nm pores of a NP with gyroid morphology...... the hydrolysis of PLLA. The obtained release profiles demonstrate that the degradation of PLLA in nanoporous confinement is significantly slower than the degradation of unconfined PLLA. The release of R6G encapsulated in PLLA becomes correspondingly slower, while the initial burst release virtually disappears...

  12. Microencapsulation of chemotherapeutics into monodisperse and tunable biodegradable polymers via electrified liquid jets: control of size, shape, and drug release.

    Science.gov (United States)

    Fattahi, Pouria; Borhan, Ali; Abidian, Mohammad Reza

    2013-09-06

    This paper describes microencapsulation of antitumor agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, Carmustine) into biodegradable polymer poly(lactic-co-glycolic) acid (PLGA) using an electrojetting technique. The resulting BCNU-loaded PLGA microcapsules have significantly higher drug encapsulation efficiency, more tunable drug loading capacity, and (3) narrower size distribution than those generated using other encapsulation methods. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. 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.

  14. Structural and chemical aspects of HPMA copolymers as drug carriers

    Czech Academy of Sciences Publication Activity Database

    Ulbrich, Karel; Šubr, Vladimír

    2010-01-01

    Roč. 62, č. 17 (2010), s. 150-166 ISSN 0169-409X R&D Projects: GA AV ČR KAN200200651; GA AV ČR IAAX00500803 Institutional research plan: CEZ:AV0Z40500505 Keywords : drug-delivery systems * N-(2-hydroxypropyl)methacrylamide * polymer drug conjugates Subject RIV: CD - Macromolecular Chemistry Impact factor: 13.577, year: 2010

  15. Kinetic models for the release of the anticancer drug doxorubicin from biodegradable polylactide/metal oxide-based hybrids

    CSIR Research Space (South Africa)

    Mhlanga, N

    2015-01-01

    Full Text Available For decades, studies on drug-release kinetics have been an important topic in the field of drug delivery because they provide important insights into the mechanism of drug release from carriers. In this work, polylactide (PLA), doxorubicin (DOX...

  16. Biodegradable nanoparticles for gene therapy technology

    International Nuclear Information System (INIS)

    Hosseinkhani, Hossein; He, Wen-Jie; Chiang, Chiao-Hsi; Hong, Po-Da; Yu, Dah-Shyong; Domb, Abraham J.; Ou, Keng-Liang

    2013-01-01

    Rapid propagations in materials technology together with biology have initiated great hopes in the possibility of treating many diseases by gene therapy technology. Viral and non-viral gene carriers are currently applied for gene delivery. Non-viral technology is safe and effective for the delivery of genetic materials to cells and tissues. Non-viral systems are based on plasmid expression containing a gene encoding a therapeutic protein and synthetic biodegradable nanoparticles as a safe carrier of gene. Biodegradable nanoparticles have shown great interest in drug and gene delivery systems as they are easy to be synthesized and have no side effect in cells and tissues. This review provides a critical view of applications of biodegradable nanoparticles on gene therapy technology to enhance the localization of in vitro and in vivo and improve the function of administered genes

  17. From Composition to Cure: A Systems Engineering Approach to Anticancer Drug Carriers.

    Science.gov (United States)

    MacEwan, Sarah R; Chilkoti, Ashutosh

    2017-06-06

    The molecular complexity and heterogeneity of cancer has led to a persistent, and as yet unsolved, challenge to develop cures for this disease. The pharmaceutical industry focuses the bulk of its efforts on the development of new drugs, but an alternative approach is to improve the delivery of existing drugs with drug carriers that can manipulate when, where, and how a drug exerts its therapeutic effect. For the treatment of solid tumors, systemically delivered drug carriers face significant challenges that are imposed by the pathophysiological barriers that lie between their site of administration and their site of therapeutic action in the tumor. Furthermore, drug carriers face additional challenges in their translation from preclinical validation to clinical approval and adoption. Addressing this diverse network of challenges requires a systems engineering approach for the rational design of optimized carriers that have a realistic prospect for translation from the laboratory to the patient. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

    Chen, Xinli; Liu, Lisha; Jiang, Chen

    2016-07-01

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

  19. Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers

    Directory of Open Access Journals (Sweden)

    Wahajuddin

    2012-07-01

    Full Text Available Wahajuddin,1,2 Sumit Arora21Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 2Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Rae Bareli, IndiaAbstract: A targeted drug delivery system is the need of the hour. Guiding magnetic iron oxide nanoparticles with the help of an external magnetic field to its target is the principle behind the development of superparamagnetic iron oxide nanoparticles (SPIONs as novel drug delivery vehicles. SPIONs are small synthetic γ-Fe2O3 (maghemite or Fe3O4 (magnetite particles with a core ranging between 10 nm and 100 nm in diameter. These magnetic particles are coated with certain biocompatible polymers, such as dextran or polyethylene glycol, which provide chemical handles for the conjugation of therapeutic agents and also improve their blood distribution profile. The current research on SPIONs is opening up wide horizons for their use as diagnostic agents in magnetic resonance imaging as well as for drug delivery vehicles. Delivery of anticancer drugs by coupling with functionalized SPIONs to their targeted site is one of the most pursued areas of research in the development of cancer treatment strategies. SPIONs have also demonstrated their efficiency as nonviral gene vectors that facilitate the introduction of plasmids into the nucleus at rates multifold those of routinely available standard technologies. SPION-induced hyperthermia has also been utilized for localized killing of cancerous cells. Despite their potential biomedical application, alteration in gene expression profiles, disturbance in iron homeostasis, oxidative stress, and altered cellular responses are some SPION-related toxicological aspects which require due consideration. This review provides a comprehensive understanding of SPIONs with regard to their method of preparation, their utility as drug delivery vehicles, and some concerns which need to

  20. Scaffold: a novel carrier for cell and drug delivery.

    Science.gov (United States)

    Garg, Tarun; Singh, Onkar; Arora, Saahil; Murthy, R

    2012-01-01

    Scaffolds are implants or injects, which are used to deliver cells, drugs, and genes into the body. Different forms of polymeric scaffolds for cell/drug delivery are available: (1) a typical three-dimensional porous matrix, (2) a nanofibrous matrix, (3) a thermosensitive sol-gel transition hydrogel, and (4) a porous microsphere. A scaffold provides a suitable substrate for cell attachment, cell proliferation, differentiated function, and cell migration. Scaffold matrices can be used to achieve drug delivery with high loading and efficiency to specific sites. Biomaterials used for fabrication of scaffold may be natural polymers such as alginate, proteins, collagens, gelatin, fibrins, and albumin, or synthetic polymers such as polyvinyl alcohol and polyglycolide. Bioceramics such as hydroxyapatites and tricalcium phosphates also are used. Techniques used for fabrication of a scaffold include particulate leaching, freeze-drying, supercritical fluid technology, thermally induced phase separation, rapid prototyping, powder compaction, sol-gel, and melt moulding. These techniques allow the preparation of porous structures with regular porosity. Scaffold are used successfully in various fields of tissue engineering such as bone formation, periodontal regeneration, repair of nasal and auricular malformations, cartilage development, as artificial corneas, as heart valves, in tendon repair ,in ligament replacement, and in tumors. They also are used in joint pain inflammation, diabetes, heart disease, osteochondrogenesis, and wound dressings. Their application of late has extended to delivery of drugs and genetic materials, including plasmid DNA, at a controlled rate over a long period of time. In addition, the incorporation of drugs (i.e., inflammatory inhibitors and/or antibiotics) into scaffolds may be used to prevent infection after surgery and other disease for longer duration. Scaffold also can be used to provide adequate signals (e.g., through the use of adhesion

  1. Backbone-hydrazone-containing biodegradable copolymeric micelles for anticancer drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jing; Luan, Shujuan; Qin, Benkai; Wang, Yingying; Wang, Kai; Qi, Peilan; Song, Shiyong, E-mail: pharmsong@henu.edu.cn [Henan University, Institute of Pharmacy (China)

    2016-11-15

    Well-defined biodegradable, pH-sensitive amphiphilic block polymers, poly(ethylene glycol)-Hyd-poly(lactic acid) (mPEG-Hyd-PLA) which have acid-cleavable linkages in their backbones, were synthesized via ring-opening polymerization initiated from hydrazone-containing macroinitiators. Introducing a hydrazone bond onto the backbone of an amphiphilic copolymer will find a broad-spectrum encapsulation of hydrophobic drugs. Dynamic light scattering (DLS) and transmission electron microscopy showed that the diblock copolymers self-assembled into stable micelles with average diameters of 100 nm. The mean diameters and size distribution of the hydrazone-containing micelles changed obviously in mildly acidic pH (multiple peaks from 1 to 202 nm appeared under a pH 4.0 condition) than in neutral, while there were no changes in the case of non-sensitive ones. Doxorubicin (DOX) and paclitaxel (PTX) were loaded with drug loading content ranging from 2.4 to 3.5 %, respectively. Interestingly, the anticancer drugs released from mPEG-Hyd-PLA micelles could also be promoted by the increased acidity. An in vitro cytotoxicity study showed that the DOX-loaded mPEG-Hyd-PLA micelles have significantly enhanced cytotoxicity against HepG2 cells compared with the non-sensitive poly(ethylene glycol)-block-poly(lactic acid) (mPEG-PLA) micelles. Confocal microscopy observation indicated that more DOX were delivered into the nuclei of cells following 6 or 12 h incubation with DOX-loaded mPEG-Hyd-PLA micelles. In vivo studies on H22-bearing Swiss mice demonstrated the superior anticancer activity of DOX-loaded mPEG-Hyd-PLA micelles over free DOX and DOX-loaded mPEG-PLA micelles. These hydrazone-containing pH-responsive degradable micelles provide a useful strategy for antitumor drug delivery.

  2. Synthesis of Biodegradable Polymer Micro- and Nanoparticles for Controlled Drug Delivery by Multiplexed Electrosprays

    Science.gov (United States)

    Almeria, Begona

    The goal of controlled drug delivery is to administer sustained amounts of a therapeutic agent over a prolonged period of time, improving the drug efficacy as compared to conventional, bolus doses that lead to variable concentrations of drug in blood. Although there are several systems capable to provide such a continuous-dose-based treatment, the use of biodegradable polymer micro- and, especially, nanoparticles offers multiple advantages with respect to other platforms. Their small size allows them to pass through physical barriers in the body and reach the site of treatment, allowing for a localized delivery, reducing side effects and toxicity. Polymer nanoparticles have lower clearance by the immune system, and are especially useful in intracellular delivery, delivery to the lymphatic system and the treatment of tumors, where the site of treatment is difficult to reach by larger particles. Conventional methods for biodegradable particle production rely predominately on batch, emulsion preparation methods and suffer from several shortcomings: low encapsulation efficiency (˜10% for hydrophilic drugs), difficulty to generate sufficiently small (dthe micro scale, and poor repeatability. We have developed an alternative process based on electrospray (ES) that offers distinct advantages and overcomes all of these limitations. We demonstrate this process with the Poly(DL-lactic-co-glycolic acid) (PLGA) system encapsulating agents such as Doxorubicin, Rhodamine B and Rhodamine B octadecyl ester prechlorate. We also employ this method for the generation of theranostic systems that combine their therapeutic mission with imaging capabilities to detect the biodistribution of particles inside the body. PLGA microparticles in different sizes, morphologies and compactness are generated using the electrospray-drying route. The size of the synthesized particles is primarily controlled by the delicate tuning of the solution physical properties and the ES operational parameters

  3. Structural analysis of nanoparticulate carriers for encapsulation of macromolecular drugs

    Czech Academy of Sciences Publication Activity Database

    Angelov, Borislav; Garamus, V.M.; Drechsler, M.; Angelova, A.

    2017-01-01

    Roč. 235, Jun (2017), s. 83-89 ISSN 0167-7322 R&D Projects: GA MŠk EF15_003/0000447; GA MŠk EF15_008/0000162 Grant - others:OP VVV - ELIBIO(XE) CZ.02.1.01/0.0/0.0/15_003/0000447; ELI Beamlines(XE) CZ.02.1.01/0.0/0.0/15_008/0000162 Institutional support: RVO:68378271 Keywords : self-assembled nanocarriers * liquid crystalline phase transitions * cationic lipids * macromolecular drugs Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 3.648, year: 2016

  4. Hollow Polyelectrolyte Microcapsules as Advanced Drug Delivery Carriers.

    Science.gov (United States)

    Yu, Wei; Chen, Ying; Mao, Zhengwei

    2016-06-01

    Polyelectrolyte microcapsules based layer-by-layer assembly method have many applications in biomedical field. This review mainly focuses on the recent development of polyelectrolyte microcapsules addressing the potential challenge regarding efficient drug delivery. Firstly, the paper describes the new design criteria of polyelectrolyte microcapsules for advanced functionality, especially stimuli-responsive capsules. Secondly, the surface decoration of capsules is discussed with respect to the requirement of improved biocompatibility and specific targeting. Thirdly, the mutual interaction between capsules and cells such as cell uptake are discussed. Finally, the applications of capsules in vitro and even in vivo are presented.

  5. Nanoporous materials modified with biodegradable polymers as models for drug delivery applications.

    Science.gov (United States)

    Gruber, Mathias F; Schulte, Lars; Ndoni, Sokol

    2013-04-01

    Polymers play a central role in the development of carriers for diagnostic and therapeutic agents. Especially the use of either degradable polymers or porous materials to encapsulate drug compounds in order to obtain steady drug release profiles has received much attention. We present here a proof of principle for a system combining these two encapsulation methods and consisting of a nanoporous polymer (NP) with the pores filled with a degradable polymer mixed with a drug model. Rhodamine 6G (R6G) mixed with Poly(L-Lactic Acid) (PLLA) were confined within the 14 nm pores of a NP with gyroid morphology derived from a diblock copolymer precursor. Glass transition, crystallization and melting of free and confined PLLA were monitored by differential scanning calorimetry. Release profiles for R6G were measured in methanol-water solvents at pH 13, which works as an accelerated release test by speeding up the hydrolysis of PLLA. The obtained release profiles demonstrate that the degradation of PLLA in nanoporous confinement is significantly slower than the degradation of unconfined PLLA. The release of R6G encapsulated in PLLA becomes correspondingly slower, while the initial burst release virtually disappears. These findings suggest that the presented proof of principle constitutes a promising basis for the development of novel implantable drug delivery systems. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Crystal engineering of lactose using electrospray technology: carrier for pulmonary drug delivery.

    Science.gov (United States)

    Patil, Sharvil; Mahadik, Abhijeet; Nalawade, Pradeep; More, Priyesh

    2017-12-01

    Dry powder inhalers (DPIs) consisting of a powder mixture containing coarse carrier particles (generally lactose) and micronized drug particles are used for lung drug delivery. The effective drug delivery to the lungs depends on size and shape of carrier particles. Thus, various methods have been proposed for engineering lactose particles to enhance drug delivery to lungs. The objective of current work was to assess suitability of electrospray technology toward crystal engineering of lactose. Further, utility of the prepared lactose particles as a carrier in DPI was evaluated. Saturated lactose solutions were electrosprayed to obtain electrosprayed lactose (EL) particles. The polymorphic form of EL was determined using Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry. In addition, morphological, surface textural, and flow properties of EL were determined using scanning electron microscopy and Carr's index, respectively. The aerosolization properties of EL were determined using twin-stage impinger and compared with commercial lactose particles [Respitose ® (SV003, Goch, Germany)] used in DPI formulations. EL was found to contain both isomers (α and β) of lactose having flow properties comparable to Respitose ® (SV003). In addition, the aerosolization properties of EL were found to be significantly improved when compared to Respitose ® (SV003) which could be attributed to morphological (high elongation ratio) and surface characteristic (smooth surface) alterations induced by electrospray technology. Electrospray technology can serve as an alternative technique for continuous manufacturing of engineered lactose particles which can be used as a carrier in DPI formulations.

  7. A water-soluble pillar[5]arene as a new carrier for an old drug.

    Science.gov (United States)

    Barbera, Lucia; Franco, Domenico; De Plano, Laura M; Gattuso, Giuseppe; Guglielmino, Salvatore P P; Lentini, Germana; Manganaro, Nadia; Marino, Nino; Pappalardo, Sebastiano; Parisi, Melchiorre F; Puntoriero, Fausto; Pisagatti, Ilenia; Notti, Anna

    2017-04-11

    The remarkable affinity of deca-carboxylatopillar[5]arene WP5 towards the aminoglycoside antibiotic, amikacin, in aqueous media is reported; in vitro studies on Gram-positive bacteria (Staphylococcus aureus) show that drug entrapment inside WP5 also takes place in the presence of the microrganisms, thus pointing to WP5 as an appealing carrier for amikacin targeted delivery.

  8. Target Nanoparticles for Therapy - SANS and DLS of Drug Carrier Liposomes and Polymer Nanoparticles

    Science.gov (United States)

    Nawroth, T.; Johnson, R.; Krebs, L.; Khoshakhlagh, P.; Langguth, P.; Hellmann, N.; Goerigk, G.; Boesecke, P.; Bravin, A.; Le Duc, G.; Szekely, N.; Schweins, R.

    2016-09-01

    T arget Nano-Pharmaceutics shall improve therapy and diagnosis of severe diseases, e.g. cancer, by individual targeting of drug-loaded nano-pharmaceuticals towards cancer cells, and drug uptake receptors in other diseases. Specific ligands, proteins or cofactors, which are recognized by the diseased cells or cells of food and drug uptake, are bound to the nanoparticle surface, and thus capable of directing the drug carriers. The strategy has two branches: a) for parenteral cancer medicine a ligand set (2-5 different, surface-linked) are selected according to the biopsy analysis of the patient tissue e.g. from tumor.; b) in the oral drug delivery part the drug transport is enforced by excipients/ detergents in combination with targeting materials for cellular receptors resulting in an induced drug uptake. Both targeting nanomaterials are characterized by a combination of SANS + DLS and SAXS or ASAXS in a feedback process during development by synthesis, nanoparticle assembly and formulation.

  9. Target Nanoparticles for Therapy - SANS and DLS of Drug Carrier Liposomes and Polymer Nanoparticles

    International Nuclear Information System (INIS)

    Nawroth, T; Johnson, R; Krebs, L; Khoshakhlagh, P; Langguth, P; Hellmann, N; Goerigk, G; Boesecke, P; Bravin, A; Duc, G Le; Szekely, N; Schweins, R

    2016-01-01

    T arget Nano-Pharmaceutics shall improve therapy and diagnosis of severe diseases, e.g. cancer, by individual targeting of drug-loaded nano-pharmaceuticals towards cancer cells, and drug uptake receptors in other diseases. Specific ligands, proteins or cofactors, which are recognized by the diseased cells or cells of food and drug uptake, are bound to the nanoparticle surface, and thus capable of directing the drug carriers. The strategy has two branches: a) for parenteral cancer medicine a ligand set (2-5 different, surface-linked) are selected according to the biopsy analysis of the patient tissue e.g. from tumor.; b) in the oral drug delivery part the drug transport is enforced by excipients/ detergents in combination with targeting materials for cellular receptors resulting in an induced drug uptake. Both targeting nanomaterials are characterized by a combination of SANS + DLS and SAXS or ASAXS in a feedback process during development by synthesis, nanoparticle assembly and formulation. (paper)

  10. Polymer coating of carrier excipients modify aerosol performance of adhered drugs used in dry powder inhalation therapy.

    Science.gov (United States)

    Traini, Daniela; Scalia, Santo; Adi, Handoko; Marangoni, Elisabetta; Young, Paul M

    2012-11-15

    The potential of excipient coating to enhance aerosol performance of micronized drugs in carrier excipient-drug blends, used in dry powder inhalers, was investigated. Both EC (ethyl cellulose) and PVP (polyvinylpyrrolidone) were used as coating agents. Carriers were prepared via sieve fractioning followed by spray drying, with and without polymer additive. Each uncoated and coated carrier salbutamol sulphate (SS) blended systems were evaluated for particle size, morphology, drug carrier adhesion and aerosolisation performance, after blending and storage for 24h. All carrier-based systems prepared had similar particle sizes and morphologies. The surface chemistries of the carriers were significantly different, as was drug-carrier adhesion and aerosolisation performance. Particle adhesion between SS and aerosol performance (fine particle fraction; FPF) followed the rank: PVP coated>un-coated>EC coated lactose. This rank order could be attributed to the surface energy measured by contact goniometry and related to the chemistry of lactose and each polymer. Storage did not significantly affect aerosol performance, however a rank increase in mean FPF value was observed for uncoated and EC coated lactose. Finally, the net electrostatic charge across the aerosol cloud indicated that the EC coated lactose transferred less charge to SS particles. The performance of each carrier system could be attributed to the carrier surface chemistry and, in general, by careful selection of the coating polymer, drug-carrier adhesion, electrostatic charge and aerosol performance could be controlled. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Biodegradable shape-memory polymers exhibiting sharp thermal transitions and controlled drug release.

    Science.gov (United States)

    Nagahama, Koji; Ueda, Yuichi; Ouchi, Tatsuro; Ohya, Yuichi

    2009-07-13

    Biodegradable shape-memory polymer networks prepared by cross-linking star shape branched oligo(ε-caprolactone) (bOCL) with hexamethylene diisocyanate are introduced. The thermal and mechanical properties of these networks were investigated using differential scanning calorimetry and tensile testing, respectively, and the morphology of the phase structure was characterized by polarized optical microscopy. The shape-memory properties of the networks were quantified using thermomechanical tensile experiments and showed strain fixity rates R(f) higher than 97% and strain recovery rates R(r) as high as 100%. Of note, networks of OCL segments with a lower degree of polymerization (DP; 10) exhibited significantly improved temperature-sensitive shape recovery: 90% of the permanent shape was recovered upon heating to within a 2 °C range (37-39 °C). The networks exhibited complete shape recovery to the permanent shape within 10 s at 42 °C. Theophylline-loaded (10 and 20 wt %) shape-memory materials, prepared by cross-linking bOCL with hexamethylene diisocyanate in the presence of theophylline, are also described as a model for a controlled drug release device. The 10 wt % loaded material was sufficiently soft and flexible for complex shape transformation and also showed high R(f) (98%) and R(r) (99%). Sustained release of loaded theophylline was achieved over 1 month without initial burst-release in a phosphate buffer solution (PBS; pH 7.4) at 37 °C.

  12. Characterization of Different Functionalized Lipidic Nanocapsules as Potential Drug Carriers

    Directory of Open Access Journals (Sweden)

    José Manuel Peula-García

    2012-02-01

    Full Text Available Lipid nanocapsules (LNC based on a core-shell structure consisting of an oil-filled core with a surrounding polymer layer are known to be promising vehicles for the delivery of hydrophobic drugs in the new therapeutic strategies in anti-cancer treatments. The present work has been designed as basic research about different LNC systems. We have synthesized—and physico-chemically characterized—three different LNC systems in which the core was constituted by olive oil and the shell by different phospholipids (phosphatidyl-serine or lecithin and other biocompatible molecules such as Pluronic® F68 or chitosan. It is notable that the olive-oil-phosphatidyl-serine LCN is a novel formulation presented in this work and was designed to generate an enriched carboxylic surface. This carboxylic layer is meant to link specific antibodies, which could facilitate the specific nanocapsule uptake by cancer cells. This is why nanoparticles with phosphatidyl-serine in their shell have also been used in this work to form immuno-nanocapsules containing a polyclonal IgG against a model antigen (C-reactive protein covalently bounded by means of a simple and reproducible carbodiimide method. An immunological study was made to verify that these IgG-LNC complexes showed the expected specific immune response. Finally, a preliminary in vitro study was performed by culturing a breast-carcinoma cell line (MCF-7 with Nile-Red-loaded LNC. We found that these cancer cells take up the fluorescent Nile-Red molecule in a process dependent on the surface properties of the nanocarriers.

  13. Design of Chitosan and Its Water Soluble Derivatives-Based Drug Carriers with Polyelectrolyte Complexes

    Directory of Open Access Journals (Sweden)

    Qing-Xi Wu

    2014-12-01

    Full Text Available Chitosan, the cationic polysaccharide derived from the natural polysaccharide chitin, has been studied as a biomaterial for more than two decades. As a polycationic polymer with favorable properties, it has been widely used to form polyelectrolyte complexes with polyanions for various applications in drug delivery fields. In recent years, a growing number of studies have been focused on the preparation of polyelectrolyte complexes based on chitosan and its water soluble derivatives. They have been considered well-suited as biomaterials for a number of vital drug carriers with targeted/controlled release profiles, e.g., films, capsules, microcapsules. In this work, an overview highlights not only the favorable properties of chitosan and its water soluble derivatives but also the good performance of the polyelectrolyte complexes produced based on chitosan. Their various types of applications as drug carriers are reviewed in detail.

  14. Design of Chitosan and Its Water Soluble Derivatives-Based Drug Carriers with Polyelectrolyte Complexes

    Science.gov (United States)

    Wu, Qing-Xi; Lin, Dong-Qiang; Yao, Shan-Jing

    2014-01-01

    Chitosan, the cationic polysaccharide derived from the natural polysaccharide chitin, has been studied as a biomaterial for more than two decades. As a polycationic polymer with favorable properties, it has been widely used to form polyelectrolyte complexes with polyanions for various applications in drug delivery fields. In recent years, a growing number of studies have been focused on the preparation of polyelectrolyte complexes based on chitosan and its water soluble derivatives. They have been considered well-suited as biomaterials for a number of vital drug carriers with targeted/controlled release profiles, e.g., films, capsules, microcapsules. In this work, an overview highlights not only the favorable properties of chitosan and its water soluble derivatives but also the good performance of the polyelectrolyte complexes produced based on chitosan. Their various types of applications as drug carriers are reviewed in detail. PMID:25532565

  15. Montelukast-loaded nanostructured lipid carriers: part II pulmonary drug delivery and in vitro-in vivo aerosol performance.

    Science.gov (United States)

    Patil-Gadhe, Arpana; Kyadarkunte, Abhay; Patole, Milind; Pokharkar, Varsha

    2014-09-01

    The aim of the present study was to establish the potential of montelukast loaded nanostructured lipid carrier (MNLC) for pulmonary application. The formulated nanoparticles were evaluated in vitro for aerodynamic characterization and in vivo for pulmokinetics in Wistar rats. The in vitro cytotoxicity was performed on A549 cell line and compared with montelukast-aqueous solution. MNLC was prepared with montelukast (0.2%), Precirol ATO5 (solid lipid), and Capryol-90 (liquid lipid) in the ratio of 7:3 using melt-emulsification-homogenization method. dl-Pyrrolidonecarboxylic acid salt of l-cocyl arginine ethyl ester (CAE), a biodegradable surfactant in the concentration of 1% was used to stabilize the nanoparticles. The particle size and encapsulation efficiency (EE) were 184.6 ± 2.7 nm and >95%, respectively. MNLC-Dry powder for inhalation (DPI) was prepared by lyophilization using 3% mannitol as cryoprotectant and carrier. MNLC-DPI was evaluated for flow, crystallographic and thermal properties. Mass median diameters (MMD) and density for MNLC-DPI were found to be 15.1 ± 1.4 μm and 0.051 ± 0.002 g/cc, respectively. In vitro aerosol performance study indicated more than 95% of the emitted dose (ED) at both the flow rates studied. Mass median aerodynamic diameters (MMAD) of 3.24 ± 0.67 μm with 69.98 ± 1.9% fine particle fraction (FPF) were obtained at 30 L/min flow rate, whereas at 60 L/min MMAD and FPF were found to be 2.83 ± 0.46 μm and 90.22 ± 2.6%, respectively. In vitro cytotoxicity study on A549 cells revealed higher safety of MNLC than pure drug. The pulmonary pharmacokinetic study demonstrated improved bioavailability, longer residence of drug in the lung and targeting factor of 11.76 for MNLC as compared to montelukast-aqueous solution. Thus, the results of the study demonstrated the potential of montelukast lipidic nanoparticulate formulation to improve the efficacy with reduced toxicity leading to better performance of drug as MNLC-DPI for

  16. Sodium montmorillonite/amine-containing drugs complexes: new insights on intercalated drugs arrangement into layered carrier material.

    Directory of Open Access Journals (Sweden)

    Murilo L Bello

    Full Text Available Layered drug delivery carriers are current targets of nanotechnology studies since they are able to accommodate pharmacologically active substances and are effective at modulating drug release. Sodium montmorillonite (Na-MMT is a clay that has suitable properties for developing new pharmaceutical materials due to its high degree of surface area and high capacity for cation exchange. Therefore Na-MMT is a versatile material for the preparation of new drug delivery systems, especially for slow release of protonable drugs. Herein, we describe the intercalation of several amine-containing drugs with Na-MMT so we can derive a better understanding of how these drugs molecules interact with and distribute throughout the Na-MMT interlayer space. Therefore, for this purpose nine sodium montmorillonite/amine-containing drugs complexes (Na-MMT/drug were prepared and characterized. In addition, the physicochemical properties of the drugs molecules in combination with different experimental conditions were assessed to determine how these factors influenced experimental outcomes (e.g. increase of the interlayer spacing versus drugs arrangement and orientation. We also performed a molecular modeling study of these amine-containing drugs associated with different Na-MMT/drug complex models to analyze the orientation and arrangement of the drugs molecules in the complexes studied. Six amine-containing drugs (rivastigmine, doxazosin, 5-fluorouracil, chlorhexidine, dapsone, nystatin were found to successfully intercalate Na-MMT. These findings provide important insights on the interlayer aspect of the molecular systems formed and may contribute to produce more efficient drug delivery nanosystems.

  17. Hydroxypropyl-β-cyclodextrin–graphene oxide conjugates: Carriers for anti-cancer drugs

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Jingting; Meng, Na; Fan, Yunting; Su, Yutian; Zhang, Ming [Jiangsu Collaborative Innovation Center for Biological Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023 (China); National and Local Joint Engineering Research Center of Biomedical Functional Materials, Nanjing 210023 (China); Jiangsu Key Laboratory of Biofunctional Materials, Jiangsu Engineering Research Center for Biomedical Function Materials, Nanjing 210023 (China); Xiao, Yinghong, E-mail: yhxiao@njnu.edu.cn [Jiangsu Collaborative Innovation Center for Biological Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023 (China); National and Local Joint Engineering Research Center of Biomedical Functional Materials, Nanjing 210023 (China); Jiangsu Key Laboratory of Biofunctional Materials, Jiangsu Engineering Research Center for Biomedical Function Materials, Nanjing 210023 (China); Zhou, Ninglin, E-mail: zhouninglin@njnu.edu.cn [Jiangsu Collaborative Innovation Center for Biological Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023 (China); National and Local Joint Engineering Research Center of Biomedical Functional Materials, Nanjing 210023 (China); Jiangsu Key Laboratory of Biofunctional Materials, Jiangsu Engineering Research Center for Biomedical Function Materials, Nanjing 210023 (China); Nanjing Zhou Ninglin Advanced Materials Technology Company Limited, Nanjing 211505 (China)

    2016-04-01

    A novel drug carrier based on hydroxypropyl-β-cyclodextrin (HP-β-CD) modified carboxylated graphene oxide (GO-COOH) was designed to incorporate anti-cancer drug paclitaxel (PTX). The formulated nanomedicines were characterized by Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). Results showed that PTX can be incorporated into GO-COO-HP-β-CD nanospheres successfully, with an average diameter of about 100 nm. The solubility and stability of PTX-loaded GO-COO-HP-β-CD nanospheres in aqueous media were greatly enhanced compared with the untreated PTX. The results of hemolysis test demonstrated that the drug-loaded nanospheres were qualified with good blood compatibility for intravenous use. In vitro anti-tumor activity was measured and results demonstrated that the incorporation of PTX into the newly developed GO-COO-HP-β-CD carrier could confer significantly improved cytotoxicity to the nanosystem against tumor cells than single application of PTX. GO-COO-HP-β-CD nanospheres may represent a promising formulation platform for a broad range of therapeutic agent, especially those with poor solubility. - Highlights: • Hydroxypropyl-β-cyclodextrin (HP-β-CD) modified carboxylated graphene oxide (GO-COOH) was designed as a drug carrier. • The prepared PTX-loaded nanospheres can be dispersed in aqueous medium stably. • The GO-COO-HP-β-CD nanospheres are safe for blood-contact applications. • This newly developed PTX-delivery system could confer significantly improved cytotoxicity against tumor cells.

  18. Syntheses and Characterizations of Smart and Biodegradable Dendritic Nanoparticles for Controlled Drug Delivery

    National Research Council Canada - National Science Library

    Kim, Y

    2003-01-01

    ... (LCST) measured by UV-VIS spectroscopy. The LCST depended on the concentrations of the dendrimer. The dendrimer also demonstrated biodegradable properties with decreasing their molar mass as a function of time.

  19. An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Juan P de Macêdo

    2015-05-01

    Full Text Available Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candidate mediating the action of a group of anti-parasitic choline analogs. Depletion of TbMCP14 by inducible RNAi in both bloodstream and procyclic forms increased resistance of parasites towards the compounds by 7-fold and 3-fold, respectively, compared to uninduced cells. In addition, down-regulation of TbMCP14 protected bloodstream form mitochondria from a drug-induced decrease in mitochondrial membrane potential. Conversely, over-expression of the carrier in procyclic forms increased parasite susceptibility more than 13-fold. Metabolomic analyses of parasites over-expressing TbMCP14 showed increased levels of the proline metabolite, pyrroline-5-carboxylate, suggesting a possible involvement of TbMCP14 in energy production. The generation of TbMCP14 knock-out parasites showed that the carrier is not essential for survival of T. brucei bloodstream forms, but reduced parasite proliferation under standard culture conditions. In contrast, depletion of TbMCP14 in procyclic forms resulted in growth arrest, followed by parasite death. The time point at which parasite proliferation stopped was dependent on the major energy source, i.e. glucose versus proline, in the culture medium. Together with our findings that proline-dependent ATP production in crude mitochondria from TbMCP14-depleted trypanosomes was reduced compared to control mitochondria, the study demonstrates that TbMCP14 is involved in energy production in T. brucei. Since TbMCP14 belongs to a trypanosomatid-specific clade of mitochondrial carrier family proteins showing very poor similarity to mitochondrial carriers of mammals, it may represent an interesting target for drug

  20. Curcumin drug delivery by vanillin-chitosan coated with calcium ferrite hybrid nanoparticles as carrier.

    Science.gov (United States)

    Kamaraj, Sriram; Palanisamy, Uma Maheswari; Kadhar Mohamed, Meera Sheriffa Begum; Gangasalam, Arthanareeswaran; Maria, Gover Antoniraj; Kandasamy, Ruckmani

    2018-04-30

    The aim of the present investigation is the development, optimization and characterization of curcumin-loaded hybrid nanoparticles of vanillin-chitosan coated with super paramagnetic calcium ferrite. The functionally modified vanillin-chitosan was prepared by the Schiff base reaction to enhance the hydrophobic drug encapsulation efficiency. Calcium ferrite (CFNP) nano particles were added to the vanillin modified chitosan to improve the biocompatibility. The vanillin-chitosan-CFNP, hybrid nanoparticle carrier was obtained by ionic gelation method. Characterizations of the hybrid materials were performed by XRD, FTIR, 1 H NMR, TGA, AFM and SEM techniques to ensure the modifications on the chitosan material. Taguchi method was applied to optimize the drug (curcumin) encapsulation efficiency by varying the drug to chitosan-vanillin, CFNP to chitosan-vanillin and TPP (sodium tripolyphospate) to chitosan-vanillin ratios. The maximum encapsulation efficiency was obtained as 98.3% under the conditions of 0.1, 0.75 and 1.0 for the drug to chitosan-vanillin, CFNP to chitosan-vanillin and TPP to chitosan-vanillin ratios, respectively. The curcumin release was performed at various pH, initial drug loading concentrations and magnetic fields. The drug release mechanism was predicted by fitting the experimental kinetic data with various drug release models. The drug release profiles showed the best fit with Higuchi model under the most of conditions. The drug release mechanism followed both non-Fickian diffusion and case II transport mechanism for chitosan, however the non-Fickian diffusion mechanism was followed for the vanillin modified chitosan. The biocompatibility of the hybrid material was tested using L929 fibroblast cells. The cytotoxicity test was performed against MCF-7 breast cancer cell line to check the anticancer property of the hybrid nano carrier with the curcumin drug. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Cyclodextrins as drug carriers in Pharmaceutical Technology: The state of the art.

    Science.gov (United States)

    Conceição, Jaime; Adeoye, Oluwatomide; Cabral-Marques, Helena Maria; Lobo, Jose Manuel Sousa

    2017-12-18

    Cyclodextrins (CDs) are versatile excipients with an essential role in drug delivery, as they can form non-covalently bonded inclusion complexes (host-guest complexes) with several drugs either in solution or in the solid state. The main purpose of this publication was to carry out a state of the art of CDs as complexing agents in drug carrier systems. In this way, the history, properties and pharmaceutical applications of the CDs were highlighted with typical examples. The methods to enhance the complexation efficiency (CE) and the CDs applications in solid dosage forms were emphasized in more detail. The main advantages of using these cyclic oligosaccharides are as follows: (1) to enhance solubility/dissolution/ bioavailability of poorly soluble drugs; (2) to enhance drug stability; (3) to modify the drug release site and/or time profile; and (4) to reduce drug side effects (for example, gastric or ocular irritation). These compounds present favorable toxicological profile for human use and therefore there are various medicines containing CDs approved by regulatory authorities worldwide. On the other hand, the major drawback of CDs is the increase in formulation bulk, once the CE is, in general, very low. This aspect is particularly relevant in solid dosage forms and limits the use of CDs to potent drugs. CDs have great potential as drug carriers in Pharmaceutical Technology and can be used by the formulator in order to improve the drug properties such as solubility, bioavailability and stability. Additionally, recent studies have shown that these compounds can be applied as active pharmaceutical ingredients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Red blood cells and polyelectrolyte multilayer capsules: natural carriers versus polymer-based drug delivery vehicles.

    Science.gov (United States)

    Kolesnikova, Tatiana A; Skirtach, Andre G; Möhwald, Helmuth

    2013-01-01

    Red blood cells (RBCs) and lipid-based carriers on the one hand and polymeric capsules on the other hand represent two of the most widely used carriers in drug delivery. Each class of these carriers has its own set of properties, specificity and advantages. Thorough comparative studies of such systems are reported here for the first time. In this review, RBCs are described in comparison with synthetic polymeric drug delivery vehicles using polyelectrolyte multilayer capsules as an example. Lipid-based composition of the shell in the former case is particularly attractive due to their inherent biocompatibility and flexibility of the carriers. On the other hand, synthetic approaches to fabrication of polyelectrolyte multilayer capsules permit manipulation of the permeability of their shell as well as tuning their composition, mechanical properties, release methods and targeting. In conclusion, properties of RBCs and polyelectrolyte multilayer capsules are reported here highlighting similarities and differences in their preparation and applications. In addition, their advantages and disadvantages are discussed.

  3. Interaction of tricyclic drugs with copper phthalocyanine dye immobilized on magnetic carriers

    Czech Academy of Sciences Publication Activity Database

    Šafaříková, Miroslava; Šafařík, Ivo

    3(Suppl.2), - (2002), s. 188-191 ISSN 1473-2262. [International Conference on the Scientific and Clinical Applications of Magnetic Carriers /4./. Tallahassee, 09.05.2002-11.05.2002] R&D Projects: GA MŠk OC 523.80; GA AV ČR IBS6087204 Institutional research plan: CEZ:AV0Z6087904 Keywords : magnetic * tricyclic drugs * phthalocyanine Subject RIV: CE - Biochemistry

  4. Enzyme decorated drug carriers: Targeted swords to cleave and overcome the mucus barrier.

    Science.gov (United States)

    Menzel, Claudia; Bernkop-Schnürch, Andreas

    2018-01-15

    The use of mucus permeating drug carrier systems being able to overcome the mucus barrier can lead to a remarkable enhancement in bioavailability. One promising approach is the design of mucolytic enzyme decorated carrier systems (MECS). These systems include micro- and nanoparticles as well as self-emulsifying drug delivery systems (SEDDS) decorated with mucin cleaving enzymes such as papain (PAP) or bromelain (BRO). MECS are able to cross the mucus barrier in a comparatively efficient manner by cleaving mucus substructures in front of them on their way to the epithelium. Thereby these enzymes hydrolyze peptide bonds of mucus glycoproteins forming tiny holes or passages through the mucus. In various in vitro and in vivo studies MECS proved to be superior in their mucus permeating properties over nanocarriers without enzyme decoration. PAP decorated nanoparticles, for instance, remained 3h after oral administration to an even 2.5-fold higher extend in rat small intestine than the corresponding undecorated nanoparticles permeating the intestinal mucus gel layer to a much lower degree. As MECS break up the mucus network only locally without destroying its overall protective barrier function, even long term treatments with such systems seem feasible. Within this review article we address different drug carrier systems decorated with various types of enzymes, their particular pros and cons and potential applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Modified hydrotalcite-like compounds as active fillers of biodegradable polymers for drug release and food packaging applications.

    Science.gov (United States)

    Costantino, Umberto; Nocchetti, Morena; Tammaro, Loredana; Vittoria, Vittoria

    2012-11-01

    This review treats the recent patents and related literature, mainly from the Authors laboratories, on biomedical and food packaging applications of nano-composites constituted of biodegradable polymers filled with micro or nano crystals of organically modified Layered Double Hydroxides of Hydrotalcite type. After a brief outline of the chemical and structural aspects of Hydrotalcite-like compounds (HTlc) and of their manipulation via intercalation of functional molecular anions to obtain materials for numerous, sometime unexpected applications, the review approaches the theme in three separated parts. Part 1 deals with the synthetic method used to prepare the pristine Mg-Al and Zn-Al HTlc and with the procedures of their functionalization with anti-inflammatory (diclofenac), antibacterial (chloramphenicol hemisuccinate), antifibrinolytic (tranexamic acid) drugs and with benzoates with antimicrobial activity. Procedures used to form (nano) composites of polycaprolactone, used as an example of biodegradable polymer, and functionalized HTlc are also reported. Part 2 discusses a patent and related papers on the preparation and biomedical use of a controlled delivery system of the above mentioned pharmacologically active substances. After an introduction dealing with the recent progress in the field of local drug delivery systems, the chemical and structural aspects of the patented system constituted of a biodegradable polymer and HTlc loaded with the active substances will be presented together with an extensive discussion of the drug release in physiological medium. Part 3 deals with a recent patent and related papers on chemical, structural and release property of antimicrobial species of polymeric films containing antimicrobial loaded HTlc able to act as active packaging for food products prolonging their shelf life.

  6. A Mechanistic Model for Drug Release in PLGA Biodegradable Stent Coatings Coupled with Polymer Degradation and Erosion

    Science.gov (United States)

    Zhu, Xiaoxiang; Braatz, Richard D.

    2015-01-01

    Biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) coating for applications in drug-eluting stents has been receiving increasing interest as a result of its unique properties compared with biodurable polymers in delivering drug for reducing stents-related side effects. In this work, a mathematical model for describing the PLGA degradation and erosion and coupled drug release from PLGA stent coating is developed and validated. An analytical expression is derived for PLGA mass loss that predicts multiple experimental studies in the literature. An analytical model for the change of the number-average degree of polymerization (or molecular weight) is also derived. The drug transport model incorporates simultaneous drug diffusion through both the polymer solid and the liquid-filled pores in the coating, where an effective drug diffusivity model is derived taking into account factors including polymer molecular weight change, stent coating porosity change, and drug partitioning between solid and aqueous phases. The model is used to describe in vitro sirolimus release from PLGA stent coating, and demonstrates the significance of simultaneous sirolimus release via diffusion through both polymer solid and pore space. The proposed model is compared to existing drug transport models, and the impact of model parameters, limitations and possible extensions of the model are also discussed. PMID:25345656

  7. Plant protein-based hydrophobic fine and ultrafine carrier particles in drug delivery systems.

    Science.gov (United States)

    Malekzad, Hedieh; Mirshekari, Hamed; Sahandi Zangabad, Parham; Moosavi Basri, S M; Baniasadi, Fazel; Sharifi Aghdam, Maryam; Karimi, Mahdi; Hamblin, Michael R

    2018-02-01

    For thousands of years, plants and their products have been used as the mainstay of medicinal therapy. In recent years, besides attempts to isolate the active ingredients of medicinal plants, other new applications of plant products, such as their use to prepare drug delivery vehicles, have been discovered. Nanobiotechnology is a branch of pharmacology that can provide new approaches for drug delivery by the preparation of biocompatible carrier nanoparticles (NPs). In this article, we review recent studies with four important plant proteins that have been used as carriers for targeted delivery of drugs and genes. Zein is a water-insoluble protein from maize; Gliadin is a 70% alcohol-soluble protein from wheat and corn; legumin is a casein-like protein from leguminous seeds such as peas; lectins are glycoproteins naturally occurring in many plants that recognize specific carbohydrate residues. NPs formed from these proteins show good biocompatibility, possess the ability to enhance solubility, and provide sustained release of drugs and reduce their toxicity and side effects. The effects of preparation methods on the size and loading capacity of these NPs are also described in this review.

  8. A porphyrin-based metal–organic framework as a pH-responsive drug carrier

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Wenxin [State Key Laboratory of Silicon Materials, Cyrus Tang Center for Sensor Materials and Applications, School of Materials Science & Engineering, Zhejiang University, Hangzhou 310027 (China); Hu, Quan [Department of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou 310036 (China); Jiang, Ke; Yang, Yanyu [State Key Laboratory of Silicon Materials, Cyrus Tang Center for Sensor Materials and Applications, School of Materials Science & Engineering, Zhejiang University, Hangzhou 310027 (China); Yang, Yu, E-mail: yuyang@zju.edu.cn [State Key Laboratory of Silicon Materials, Cyrus Tang Center for Sensor Materials and Applications, School of Materials Science & Engineering, Zhejiang University, Hangzhou 310027 (China); Cui, Yuanjing [State Key Laboratory of Silicon Materials, Cyrus Tang Center for Sensor Materials and Applications, School of Materials Science & Engineering, Zhejiang University, Hangzhou 310027 (China); Qian, Guodong, E-mail: gdqian@zju.edu.cn [State Key Laboratory of Silicon Materials, Cyrus Tang Center for Sensor Materials and Applications, School of Materials Science & Engineering, Zhejiang University, Hangzhou 310027 (China)

    2016-05-15

    A low cytotoxic porphyrin-based metal–organic framework (MOF) PCN-221, which exhibited high PC12 cell viability via 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyl tetrazolium (MTT) assay, was selected as an oral drug carrier. Methotrexate (MTX) was chosen as the model drug molecule which was absorbed into inner pores and channels of MOFs by diffusion. PCN-221 showed high drug loading and sustained release behavior under physiological environment without “burst effect”. The controlled pH-responsive release of drugs by PCN-221 revealed its promising application in oral drug delivery. - Graphical abstract: The porous crystals PCN-221 with pore openings (MOF) PCN-221 was prepared exhibiting low cytotoxicity. PCN-221 showed high drug Methotrexate loading and controlled pH-responsive release of Methotrexate. - Highlights: • A porphyrin-based metal–organic framework (MOF) PCN-221 was prepared showing low cytotoxicity. • PCN-221 showed high drug Methotrexate loading. • PCN-221 showed controlled pH-responsive release of Methotrexate.

  9. β-TCP porous pellets as an orthopaedic drug delivery system: ibuprofen/carrier physicochemical interactions

    International Nuclear Information System (INIS)

    Baradari, Hiba; Damia, Chantal; Dutreih-Colas, Maggy; Champion, Eric; Chulia, Dominique; Viana, Marylene

    2011-01-01

    Calcium phosphate bone substitute materials can be loaded with active substances for in situ, targeted drug administration. In this study, porous β-TCP pellets were investigated as an anti-inflammatory drug carrier. Porous β-TCP pellets were impregnated with an ethanolic solution of ibuprofen. The effects of contact time and concentration of ibuprofen solution on drug adsorption were studied. The ibuprofen adsorption equilibrium time was found to be one hour. The adsorption isotherms fitted to the Freundlich model, suggesting that the interaction between ibuprofen and β-TCP is weak. The physicochemical characterizations of loaded pellets confirmed that the reversible physisorption of ibuprofen on β-TCP pellets is due to Van der Waals forces, and this property was associated with the 100% ibuprofen release.

  10. {beta}-TCP porous pellets as an orthopaedic drug delivery system: ibuprofen/carrier physicochemical interactions

    Energy Technology Data Exchange (ETDEWEB)

    Baradari, Hiba; Damia, Chantal; Dutreih-Colas, Maggy; Champion, Eric; Chulia, Dominique; Viana, Marylene, E-mail: hiva.baradari@etu.unilim.fr [SPCTS-Centre Europeen de la Ceramique, 12 Rue Atlantis, 87068 Limoges CEDEX (France)

    2011-10-15

    Calcium phosphate bone substitute materials can be loaded with active substances for in situ, targeted drug administration. In this study, porous {beta}-TCP pellets were investigated as an anti-inflammatory drug carrier. Porous {beta}-TCP pellets were impregnated with an ethanolic solution of ibuprofen. The effects of contact time and concentration of ibuprofen solution on drug adsorption were studied. The ibuprofen adsorption equilibrium time was found to be one hour. The adsorption isotherms fitted to the Freundlich model, suggesting that the interaction between ibuprofen and {beta}-TCP is weak. The physicochemical characterizations of loaded pellets confirmed that the reversible physisorption of ibuprofen on {beta}-TCP pellets is due to Van der Waals forces, and this property was associated with the 100% ibuprofen release.

  11. A Biodegradable Microneedle Cuff for Comparison of Drug Effects through Perivascular Delivery to Balloon-Injured Arteries

    Directory of Open Access Journals (Sweden)

    Dae-Hyun Kim

    2017-02-01

    Full Text Available Restenosis at a vascular anastomosis site is a major cause of graft failure and is difficult to prevent by conventional treatment. Perivascular drug delivery has advantages as drugs can be diffused to tunica media and subintima while minimizing the direct effect on endothelium. This in vivo study investigated the comparative effectiveness of paclitaxel, sirolimus, and sunitinib using a perivascular biodegradable microneedle cuff. A total of 31 New Zealand white rabbits were used. Rhodamine was used to visualize drug distribution (n = 3. Sirolimus- (n = 7, sunitinib- (n = 7, and paclitaxel-loaded (n = 7 microneedle cuffs were placed at balloon-injured abdominal aortae and compared to drug-free cuffs (n = 7. Basic histological structures were not affected by microneedle devices, and vascular wall thickness of the device-only group was similar to that of normal artery. Quantitative analysis revealed significantly decreased neointima formation in all drug-treated groups (p < 0.001. However, the tunica media layer of the paclitaxel-treated group was significantly thinner than that of other groups and also showed the highest apoptotic ratio (p < 0.001. Proliferating cell nuclear antigen (PCNA-positive cells were significantly reduced in all drug-treated groups. Sirolimus or sunitinib appeared to be more appropriate for microneedle devices capable of slow drug release because vascular wall thickness was minimally affected.

  12. A close collaboration of chitosan with lipid colloidal carriers for drug delivery applications.

    Science.gov (United States)

    Bugnicourt, Loïc; Ladavière, Catherine

    2017-06-28

    Chitosan and lipid colloids have separately shown a growing interest in the field of drug delivery applications. Their success is mainly due to their interesting physicochemical behaviors, as well as their biological properties such as bioactivity and biocompatibility. While chitosan is a well-known cationic polysaccharide with the ability to strongly interact with drugs and biological matrices through mainly electrostatic interactions, lipid colloids are carriers particularly recognized for the drug vectorization. In recent years, the combination of both entities has been considered because it offers new systems which gather the advantages of each of them to efficiently deliver various types of bioactive species. The purpose of this review is to describe these associations between chemically-unmodified chitosan chains (solubilized or dispersed) and lipid colloids (as nanoparticles or organized in lipid layers), as well as their potential in the drug delivery area so far. Three assemblies have mainly been reported in the literature: i) lipid nanoparticles (solid lipid nanoparticles or nanostructured lipid carriers) coated with chitosan chains, ii) lipid vesicles covered with chitosan chains, and iii) chitosan chains structured in nanoparticles with a lipid coating. Their elaboration processes, their physicochemical characterization, and their biological studies are detailed and discussed herein. The different bioactive species (drugs and bio(macro)molecules) incorporated in these assemblies, their maximal incorporation efficiency, and their loading capacity are also presented. This review reveals the versatility of these assemblies. Depending on the organization of lipids (i.e., nanoparticles or vesicles) and the state of polymer chains (i.e., solubilized or dispersed under the form of nanoparticles), a large variety of drugs can be successfully incorporated, and various routes of administration can be considered. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Solid Lipid Nanoparticles of Guggul Lipid as Drug Carrier for Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Gaur

    2013-01-01

    Full Text Available Diclofenac sodium loaded solid lipid nanoparticles (SLNs were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG and plain carbopol gel containing drug (CG for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1 and stearic acid nanoparticle 1 (SAN-1 gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3 showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher Cmax than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile.

  14. Self-organized nanoparticles based on drug-interpolyelectrolyte complexes as drug carriers

    International Nuclear Information System (INIS)

    Palena, M. C.; Manzo, R. H.; Jimenez-Kairuz, A. F.

    2012-01-01

    Potential applications in drug delivery from nanostructures composed of two oppositely charged polymethacrylates, eudragit ® L100 (EL) and eudragit ® EPO (EE), loaded with three model basic drugs (D), atenolol, propranolol, and metroclopramide were evaluated. The self-organized nanoparticles based on drug-interpolyelectrolyte complexes (DIPEC), (EL-D 50 )–EE X , were obtained by mixing the aqueous dispersions of both polyelectrolytes at room temperature in an ultrasound bath. Dispersions of (EL-D 50 ) neutralized with increasing proportions of EE exhibited a rise of turbidity, particle sizes in the range of 150–400 nm, and high negative zeta potential. The sign of zeta potential was shifted from negative to positive by changes in composition of DIPEC. Freeze dried DIPEC were easily redispersed in water yielding nearly the same parameters of fresh dispersions. In vitro release experiments using Franz cells showed that DIPEC systems behave as a drug reservoir that slowly releases the drug as water is placed in the receptor compartment. The release rate was raised by ionic exchange with counterions present in simulated physiological fluids placed in the receptor media. Delivery of D from DIPEC exhibited a remarkable robustness toward simulated physiological media of different pH. The DIPEC systems exhibit interesting properties to design nanoparticulate drug delivery systems for oral and/or topical routes.

  15. Smart tetrazole-based antibacterial nanoparticles as multifunctional drug carriers for cancer combination therapy.

    Science.gov (United States)

    Zakerzadeh, Elham; Salehi, Roya; Mahkam, Mehrdad

    2017-12-01

    Due to multidrug resistance of cancer tissues and immune-suppression of cancerous patients during chemotherapy in one hand and the use of tetrazole derivatives in medicine because of its anticancer, antifungal, and antiviral properties, on the other, we were encouraged to design novel smart antibacterial nanocomposites-based polymer of tetrazole as dual anticancer drug delivery systems. The structures of nanocomposites characterized by FTIR, 1 H NMR, FESEM-EDX, and TGA analyzes and antibacterial activity of smart carriers were evaluated by determination of minimum inhibitory concentration (MIC) values against some bacteria and fungi. Then, the pH-responsive manner of both nanocomposites was proved by checking their release profiles at pH of the physiological environment (pH 7.4) and pH of tumor tissues (mildly acidic). Finally, the potential antitumoral activity of these nanocomposite systems against MCF7 cell lines was evaluated by MTT assay and cell cycle studies. The results demonstrated that the novel developed nanocomposites not only meet our expectations about simultaneous release of two anticancer drugs according to the predicted profile but also showed antibacterial and anticancer properties in vitro experimental. Moreover, it was proved that these carriers have tremendous potential in multifunctional drug delivery in cancer therapy.

  16. Controlled drug release from a novel injectable biodegradable microsphere/scaffold composite based on poly(propylene fumarate).

    Science.gov (United States)

    Kempen, Diederik H R; Lu, Lichun; Kim, Choll; Zhu, Xun; Dhert, Wouter J A; Currier, Bradford L; Yaszemski, Michael J

    2006-04-01

    The ideal biomaterial for the repair of bone defects is expected to have good mechanical properties, be fabricated easily into a desired shape, support cell attachment, allow controlled release of bioactive factors to induce bone formation, and biodegrade into nontoxic products to permit natural bone formation and remodeling. The synthetic polymer poly(propylene fumarate) (PPF) holds great promise as such a biomaterial. In previous work we developed poly(DL-lactic-co-glycolic acid) (PLGA) and PPF microspheres for the controlled delivery of bioactive molecules. This study presents an approach to incorporate these microspheres into an injectable, porous PPF scaffold. Model drug Texas red dextran (TRD) was encapsulated into biodegradable PLGA and PPF microspheres at 2 microg/mg microsphere. Five porous composite formulations were fabricated via a gas foaming technique by combining the injectable PPF paste with the PLGA or PPF microspheres at 100 or 250 mg microsphere per composite formulation, or a control aqueous TRD solution (200 microg per composite). All scaffolds had an interconnected pore network with an average porosity of 64.8 +/- 3.6%. The presence of microspheres in the composite scaffolds was confirmed by scanning electron microscopy and confocal microscopy. The composite scaffolds exhibited a sustained release of the model drug for at least 28 days and had minimal burst release during the initial phase of release, as compared to drug release from microspheres alone. The compressive moduli of the scaffolds were between 2.4 and 26.2 MPa after fabrication, and between 14.9 and 62.8 MPa after 28 days in PBS. The scaffolds containing PPF microspheres exhibited a significantly higher initial compressive modulus than those containing PLGA microspheres. Increasing the amount of microspheres in the composites was found to significantly decrease the initial compressive modulus. The novel injectable PPF-based microsphere/scaffold composites developed in this study

  17. Scintigraphic evaluation of the pharmacokinetics of a soluble polymeric drug carrier

    International Nuclear Information System (INIS)

    Pimm, M.V.; Perkins, A.C.; Hudecz, F.

    1992-01-01

    There is a growing interest in the use of macromolecular carriers for therapeutic agents. If these carriers can be labelled with an appropriate gamma-emitter, their biodistribution could be followed by scintigraphy. We have imaged the biodistribution of a synthetic branched polypeptide, based on a poly-L-lysine backbone (average molecular mass 45 kDa). The polymer was conjugated to diethylene triamine penta-acetic acid and labelled by chelation with indium-111. Mice were injected i.v. with labelled material and imaged with a gamma-camera with a pin-hole collimator. Images showed the majority of tracer remaining in the blood pool, but about 35% appeared in the urinary bladder within 1.5 h. When the 111 In-polymer was fractionated by gel filtration chromatography on S-300, the imaging showed that the early eluting material was retained, the intermediate showed some renal clearance, and the late was rapidly excreted. These findings show the value of gamma-scintigraphy for biodistribution studies with such polymeric drug carriers and its potential for clinical pharmacokinetic studies. (orig.)

  18. Drug- not carrier-dependent haematological and biochemical changes in a repeated dose study of cyclosporine encapsulated polyester nano- and micro-particles: Size does not matter

    International Nuclear Information System (INIS)

    Venkatpurwar, V.P.; Rhodes, S.; Oien, K.A.; Elliott, M.A.; Tekwe, C.D.; Jørgensen, H.G.; Kumar, M.N.V. Ravi

    2015-01-01

    Highlights: • The particulate delivery allows an increase in dose range without accrual of toxicities. • The altered haematological and biochemical changes are drug, but not particle dependent. • PLGA nano/microparticles are safe on subacute peroral dosing over 28 days. • Nano-toxicology, drug needs to be considered. - Abstract: Biodegradable nanoparticles are being considered more often as drug carriers to address pharmacokinetic/pharmacodynamic issues, yet nano-product safety has not been systematically proven. In this study, haematological, biochemical and histological parameters were examined on 28 day daily dosing of rats with nano- or micro-particle encapsulated cyclosporine (CsA) to confirm if any changes observed were drug or carrier dependent. CsA encapsulated poly(lactide-co-glycolide) [PLGA] nano- (nCsA) and micro-particles (mCsA) were prepared by emulsion techniques. CsA (15, 30, 45 mg/kg) were administered by oral gavage to Sprague Dawley (SD) rats over 28 days. Haematological and biochemical metrics were followed with tissue histology performed on sacrifice. Whether presented as nCsA or mCsA, 45 mg/kg dose caused significant loss of body weight and lowered food consumption compared to untreated control. Across the doses, both nCsA and mCsA produce significant decreases in lymphocyte numbers compared to controls, commensurate with the proprietary product, Neoral ® 15. Dosing with nCsA showed higher serum drug levels than mCsA presumably owing to the smaller particle size facilitating absorption. The treatment had no noticeable effects on inflammatory/oxidative stress markers or antioxidant enzyme levels, except an increase in ceruloplasmin (CP) levels for high dose nCsA/mCsA group. Further, only subtle, sub-lethal changes were observed in histology of nCsA/mCsA treated rat organs. Blank (drug-free) particles did not induce changes in the parameters studied. Therefore, it is extremely important that the encapsulated drug in the nano-products is

  19. C60-fullerenes as Drug Delivery Carriers for Anticancer Agents: Promises and Hurdles.

    Science.gov (United States)

    Kumar, Manish; Raza, Kaisar

    2017-01-01

    C60-fullerenes (CFs) constitute a carbon-allotropic family with cage-like fused-ring structure, comprising of 20 hexagons and 12 pentagons. Since discovery in 1985, CFs attracted the scientists from various strata for unique properties like tensile strength, nanometeric size, symmetric nature, thermal and photo conductivity, chemical tailoring opportunities and drug loading capabilities. Surprisingly, CFs are also established to possess antiviral, neuroprotective, antiinflammatory, MRI contrast and antioxidant properties. Though extensively explored for chemical modifications and therapeutic benefits, CFs and derivatives also offer immense promises in drug delivery, especially to the cancerous cells. The present review is an attempt to highlight the promises of CFs in drug delivery, esp. of anticancer agents. The review also analyzes the safety concerns of CF-based drug delivery and attempts to discuss the promises and challenges in the light of preclinical and clinical data. The raw material (research/review articles) for the manuscript was collected from Pubmed, Google scholar and Scopus and the keywords used were fullerenes, nanotechnology, nanomedicine, functionalization, safety, drug delivery and biomedical applications. The drug release rate controlling behavior, higher drug loading, immuno-neutrality, substantial biocompatibility, capability to bypass mononuclear phagocytic system, long circulating nature and tissue extraction by virtue of enhanced permeability and retention effect are the major promises of these nanocarriers. On the other hand, the concerns like elimination from the biological system, anticipated tissue toxicity, stability of the final product, sterility issues and commercial viability pose challenges in proper utilization of CFs as ideal drug delivery carriers. However, a few commercial products based on CFs with human safety evidences provide a ray of hope. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Walnut kernel-like mesoporous silica nanoparticles as effective drug carrier for cancer therapy in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Kun; Ren, Huihui; Sun, Wentong [Hebei University, Key Laboratory of Chemical Biology of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry & Environmental Science (China); Zhao, Qi [Hebei University, College of Clinical Science (China); Jia, Guang [Hebei University, Key Laboratory of Chemical Biology of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry & Environmental Science (China); Zang, Aimin [Affiliated Hospital of Hebei University (China); Zhang, Cuimiao, E-mail: cmzhanghbu@163.com; Zhang, Jinchao, E-mail: jczhang6970@163.com [Hebei University, Key Laboratory of Chemical Biology of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry & Environmental Science (China)

    2016-03-15

    In drug delivery systems, nanocarriers could reduce the degradation and renal clearance of drugs, increase the half-life in the bloodstream and payload of drugs, control the release patterns, and improve the solubility of some insoluble drugs. In particular, mesoporous silica nanoparticles (MSNs) are considered to be attractive nanocarriers for application of delivery systems because of their large surface areas, large pore volume, tunable pore sizes, good biocompatibility, and the ease of surface functionalization. However, the large-scale synthesis of monodisperse MSNs that are smaller than 200 nm remains a challenge. In this study, monodisperse walnut kernel-like MSNs with diameters of approximately 100 nm were synthesized by a sol–gel route on a large scale. The morphology and structure of MSNs were characterized by scanning electron microscope, and transmission electron microscopy, N{sub 2} adsorption–desorption isotherms, Zeta potentials, and dynamic light scattering. Drug loading and release profile, cellular uptake, subcellular localization, and anticancer effect in vitro were further investigated. The results indicated that the loading efficiency of doxorubicinhydrochloride (DOX) into the MSNs was 57 %. The MSNs–DOX delivery system exhibited a drug-pronounced initial burst release within 12 h, followed by the slow sustained release of DOX molecules; moreover, MSNs could improve DOX release efficiency in acidic medium. Most free DOX was localized in the cytoplasm, whereas the MSNs–DOX was primarily distributed in lysosome. MSNs–DOX exhibited a potential anticancer effect against MCF-7, HeLa, and A549 cells in dose- and time-dependent manners. In summary, the as-synthesized MSNs may have well function as a promising drug carrier in drug delivery fields.Graphical Abstract.

  1. Walnut kernel-like mesoporous silica nanoparticles as effective drug carrier for cancer therapy in vitro

    International Nuclear Information System (INIS)

    Ge, Kun; Ren, Huihui; Sun, Wentong; Zhao, Qi; Jia, Guang; Zang, Aimin; Zhang, Cuimiao; Zhang, Jinchao

    2016-01-01

    In drug delivery systems, nanocarriers could reduce the degradation and renal clearance of drugs, increase the half-life in the bloodstream and payload of drugs, control the release patterns, and improve the solubility of some insoluble drugs. In particular, mesoporous silica nanoparticles (MSNs) are considered to be attractive nanocarriers for application of delivery systems because of their large surface areas, large pore volume, tunable pore sizes, good biocompatibility, and the ease of surface functionalization. However, the large-scale synthesis of monodisperse MSNs that are smaller than 200 nm remains a challenge. In this study, monodisperse walnut kernel-like MSNs with diameters of approximately 100 nm were synthesized by a sol–gel route on a large scale. The morphology and structure of MSNs were characterized by scanning electron microscope, and transmission electron microscopy, N 2 adsorption–desorption isotherms, Zeta potentials, and dynamic light scattering. Drug loading and release profile, cellular uptake, subcellular localization, and anticancer effect in vitro were further investigated. The results indicated that the loading efficiency of doxorubicinhydrochloride (DOX) into the MSNs was 57 %. The MSNs–DOX delivery system exhibited a drug-pronounced initial burst release within 12 h, followed by the slow sustained release of DOX molecules; moreover, MSNs could improve DOX release efficiency in acidic medium. Most free DOX was localized in the cytoplasm, whereas the MSNs–DOX was primarily distributed in lysosome. MSNs–DOX exhibited a potential anticancer effect against MCF-7, HeLa, and A549 cells in dose- and time-dependent manners. In summary, the as-synthesized MSNs may have well function as a promising drug carrier in drug delivery fields.Graphical Abstract

  2. Vitamin B12-loaded solid lipid nanoparticles as a drug carrier in cancer therapy.

    Science.gov (United States)

    Genç, Lütfi; Kutlu, H Mehtap; Güney, Gamze

    2015-05-01

    Nanostructure-mediated drug delivery, a key technology for the realization of nanomedicine, has the potential to improve drug bioavailability, ameliorate release deviation of drug molecules and enable precision drug targeting. Due to their multifunctional properties, solid lipid nanoparticles (SLNs) have received great attention of scientists to find a solution to cancer. Vitamin supplements may contribute to a reduction in the risk of cancer. Vitamin B12 has several characteristics that make it an attractive entity for cancer treatment and possible therapeutic applications. The aim of this study was to produce B12-loaded SLNs (B12-SLNs) and determine the cytotoxic effects of B12-SLNs on H-Ras 5RP7 and NIH/3T3 control cell line. Results obtained by MTT assay, transmission electron and confocal microscopy showed that B12-loaded SLNs are more effective than free vitamin B12 on cancer cells. In addition, characterization studies indicate that while the average diameter of the B12 was about 650 nm, B12-SLNs were about 200 nm and the drug release efficiency of vit. B12 by means of SLNs increased up to 3 h. These observations point to the fact that B12-SLNs could be used as carrier systems due to the therapeutic effects on cancer.

  3. Propolis as lipid bioactive nano-carrier for topical nasal drug delivery.

    Science.gov (United States)

    Rassu, Giovanna; Cossu, Massimo; Langasco, Rita; Carta, Antonio; Cavalli, Roberta; Giunchedi, Paolo; Gavini, Elisabetta

    2015-12-01

    Propolis shows therapeutic properties ascribed to the presence of some flavonoids, phenolic acids, and their esters; it is a natural multifunctional material, solid at room temperature, and composed mainly of resin and waxes. We therefore used propolis as a lipid material to prepare solid lipid nanoparticles (SLNs); SLNs are proposed bioactive medications for topical intranasal therapy. Suitable formulation parameters were studied and the SLNs obtained by the high shear homogenization method were characterized; a selected formulation was viscosized to increase the residence time. Dimensional, morphological, and solid-state characterizations of the formulated SLNs were performed. In vitro and ex vivo permeation tests of diclofenac sodium, the model drug, and polyphenols were carried out. The propolis amount and surfactant concentration represent the key parameters that affect nanoparticle properties in terms of size, drug and polyphenol content, and physical stability. Size dispersions of about 600 nm and 0.4 PI were obtained, which do not change by increasing the viscosity. Drug is encapsulated in SLNs, as demonstrated by FTIR and DSC analyses. In vitro and ex vivo studies prove that drug and polyphenols do not cross the membranes; therefore, propolis-based SLNs could be used as delivery systems of diclofenac and flavonoids for the local treatment of nasal cavity diseases. Due to propolis composition, the proposed formulation could be used as a bioactive medication in which the carrier can exert a complementary effect with the loaded drug. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. A Review on Recent Advances in Stabilizing Peptides/Proteins upon Fabrication in Hydrogels from Biodegradable Polymers

    OpenAIRE

    Faisal Raza; Hajra Zafar; Ying Zhu; Yuan Ren; Aftab -Ullah; Asif Ullah Khan; Xinyi He; Han Han; Md Aquib; Kofi Oti Boakye-Yiadom; Liang Ge

    2018-01-01

    Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to overcome the shortcomings of old conventional dosage forms for small drugs (NSAIDS) and large peptides and proteins. The aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All...

  5. Effects of liposomes with polyisoprenoids, potential drug carriers, on the cardiovascular and excretory system in rats.

    Science.gov (United States)

    Gawrys, Olga; Polkowska, Marta; Roszkowska-Chojecka, Malwina; Gawarecka, Katarzyna; Chojnacki, Tadeusz; Swiezewska, Ewa; Masnyk, Marek; Chmielewski, Marek; Rafałowska, Janina; Kompanowska-Jezierska, Elżbieta

    2014-04-01

    The unpredictable side effects of a majority currently used drugs are the substantial issue, in which patients and physicians are forced to deal with. Augmenting the therapeutic efficacy of drugs may prove more fruitful than searching for the new ones. Since recent studies show that new cationic derivatives of polyisoprenoid alcohols (APrens) might exhibit augmenting properties, we intend to use them as a component of liposomal drug carriers. In this study we investigate if these compounds do not per se cause untoward effects on the living organism. Male Sprague-Dawley rats received for four weeks daily injections (0.5 ml sc) of liposomes built of dioleoyl phosphatidylethanolamine (DOPE), liposomes built of DOPE and APren-7 (ratio 10:1) or water solvent. Weekly, rats were observed in metabolic cages (24h); blood and urine were sampled for analysis; body weight (BW) and systolic blood pressure (SBP) were determined. After chronic experiment, kidneys and heart were harvested for histological and morphometric analysis. The 4-week BW increments were in the range of 97 ± 4 to 102 ± 4%, intergroup differences were not significant. Microalbuminuria was the lowest in the group receiving liposomes with APren-7 (0.22 ± 0.03 mg/day). Water and food intake, plasma and urine parameters were similar in all groups. Newly designed liposomes containing APren-7 did not affect functions of the excretory and cardiovascular systems, and renal morphology; therefore we find them suitable as a component of liposomal drug carriers. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  6. Coordination conjugates of therapeutic proteins with drug carriers: A new approach for versatile advanced drug delivery

    Czech Academy of Sciences Publication Activity Database

    Kejík, Z.; Bříza, T.; Králová, Jarmila; Poučková, P.; Kral, A.; Martásek, P.; Král, V.

    2011-01-01

    Roč. 21, č. 18 (2011), s. 5514-5520 ISSN 0960-894X R&D Projects: GA ČR GA203/09/1311 Grant - others:MPO(CZ) FR-TI3/521; AV ČR(CZ) KAN200100801 Program:FR; KA Institutional research plan: CEZ:AV0Z50520514 Keywords : combined cancer therapy * photodynamic therapy * targeted drug delivery Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.554, year: 2011

  7. Influence of Drug-Carrier Polymers on Alpha-Synucleinopathies: A Neglected Aspect in New Therapies Development

    Directory of Open Access Journals (Sweden)

    C. Tonda-Turo

    2018-01-01

    Full Text Available Current therapeutic strategies to treat neurodegenerative diseases, such as alpha-synucleinopathies, aim at enhancing the amount of drug reaching the brain. Methods proposed, such as intranasal administration, should be able to bypass the blood brain barrier (BBB and even when directly intracerebrally injected they could require a carrier to enhance local release of drugs. We have investigated the effect of a model synthetic hydrogel to be used as drug carrier on the amount of alpha-synuclein aggregates in cells in culture. The results indicated that alpha-synuclein aggregation was affected by the synthetic polymer, suggesting the need for testing the effect of any used material on the pathological process before its application as drug carrier.

  8. Fourth Generation Phosphorus-Containing Dendrimers: Prospective Drug and Gene Delivery Carrier

    Science.gov (United States)

    Shcharbin, D.; Dzmitruk, V.; Shakhbazau, A.; Goncharova, N.; Seviaryn, I.; Kosmacheva, S.; Potapnev, M.; Pedziwiatr-Werbicka, E.; Bryszewska, M.; Talabaev, M.; Chernov, A.; Kulchitsky, V.; Caminade, A.-M.; Majoral, J.-P.

    2011-01-01

    Research concerning new targeting delivery systems for pharmacologically active molecules and genetic material is of great importance. The aim of the present study was to investigate the potential of fourth generation (P4) cationic phosphorus-containing dendrimers to bind fluorescent probe 8-anilino-1-naphthalenesulfonate (ANS), anti-neoplastic drug cisplatin, anti-HIV siRNA siP24 and its capability to deliver green fluorescent protein gene (pGFP) into cells. The interaction between P4 and ANS (as the model drug) was investigated. The binding constant and the number of binding centers per one molecule of P4 were determined. In addition, the dendriplex between P4 and anti-HIV siRNA siP24 was characterized using circular dichroism, fluorescence polarization and zeta-potential methods; the average hydrodynamic diameter of the dendriplex was calculated using zeta-size measurements. The efficiency of transfection of pGFP using P4 was determined in HEK293 cells and human mesenchymal stem cells, and the cytotoxicity of the P4-pGFP dendriplex was studied. Furthermore, enhancement of the toxic action of the anti-neoplastic drug cisplatin by P4 dendrimers was estimated. Based on the results, the fourth generation cationic phosphorus-containing dendrimers seem to be a good drug and gene delivery carrier candidate. PMID:24310590

  9. RGD-modified lipid disks as drug carriers for tumor targeted drug delivery

    Science.gov (United States)

    Gao, Jie; Xie, Cao; Zhang, Mingfei; Wei, Xiaoli; Yan, Zhiqiang; Ren, Yachao; Ying, Man; Lu, Weiyue

    2016-03-01

    Melittin, the major component of the European bee venom, is a potential anticancer candidate due to its lytic properties. However, in vivo applications of melittin are limited due to its main side effect, hemolysis, especially when applied through intravenous administration. The polyethylene glycol-stabilized lipid disk is a novel type of nanocarrier, and the rim of lipid disks has a high affinity to amphiphilic peptides. In our study, a c(RGDyK) modified lipid disk was developed as a tumor targeted drug delivery system for melittin. Cryo-TEM was used to confirm the shape and size of lipid disks with or without c(RGDyK) modification. In vitro and in vivo hemolysis analyses revealed that the hemolysis effect significantly decreased after melittin associated with lipid disks. Importantly, the results of our in vivo biodistribution and tumor growth inhibitory experiments showed that c(RGDyK) modification increased the distribution of lipid disks in the tumor and the anticancer efficacy of melittin loaded lipid disks. Thus, we successfully achieved a targeted drug delivery system for melittin and other amphiphilic peptides with a good therapeutic effect and low side effects.

  10. Biomimetic synthesized chiral mesoporous silica: Structures and controlled release functions as drug carrier

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jing; Xu, Lu, E-mail: xl2013109@163.com; Yang, Baixue; Bao, Zhihong; Pan, Weisan; Li, Sanming, E-mail: li_sanming2013@163.com

    2015-10-01

    This work initially illustrated the formation mechanism of chiral mesoporous silica (CMS) in a brand new insight named biomimetic synthesis. Three kinds of biomimetic synthesized CMS (B-CMS, including B-CMS1, B-CMS2 and B-CMS3) were prepared using different pH or stirring rate condition, and their characteristics were tested with transmission electron microscope and small angle X-ray diffraction. The model drug indomethacin was loaded into B-CMS and drug loading content was measured using ultraviolet spectroscopy. The result suggested that pH condition influenced energetics of self-assembly process, mainly packing energetics of the surfactant, while stirring rate was the more dominant factor to determine particle length. In application, indomethacin loading content was measured to be 35.3%, 34.8% and 35.1% for indomethacin loaded B-CMS1, indomethacin loaded B-CMS2 and indomethacin loaded B-CMS3. After loading indomethacin into B-CMS carriers, surface area, pore volume and pore diameter of B-CMS carriers were reduced. B-CMS converted crystalline state of indomethacin to amorphous state, leading to the improved indomethacin dissolution. B-CMS1 controlled drug release without burst-release, while B-CMS2 and B-CMS3 released indomethacin faster than B-CMS1, demonstrating that the particle length, the ordered lever of multiple helixes, the curvature degree of helical channels and pore diameter greatly contributed to the release behavior of indomethacin loaded B-CMS. - Highlights: • Chiral mesoporous silica was synthesized using biomimetic method. • pH influenced energetics of self-assembly process of chiral mesoporous silica. • Stirring rate determined the particle length of chiral mesoporous silica. • Controlled release behaviors of chiral mesoporous silica varied based on structures.

  11. Biomimetic synthesized chiral mesoporous silica: Structures and controlled release functions as drug carrier

    International Nuclear Information System (INIS)

    Li, Jing; Xu, Lu; Yang, Baixue; Bao, Zhihong; Pan, Weisan; Li, Sanming

    2015-01-01

    This work initially illustrated the formation mechanism of chiral mesoporous silica (CMS) in a brand new insight named biomimetic synthesis. Three kinds of biomimetic synthesized CMS (B-CMS, including B-CMS1, B-CMS2 and B-CMS3) were prepared using different pH or stirring rate condition, and their characteristics were tested with transmission electron microscope and small angle X-ray diffraction. The model drug indomethacin was loaded into B-CMS and drug loading content was measured using ultraviolet spectroscopy. The result suggested that pH condition influenced energetics of self-assembly process, mainly packing energetics of the surfactant, while stirring rate was the more dominant factor to determine particle length. In application, indomethacin loading content was measured to be 35.3%, 34.8% and 35.1% for indomethacin loaded B-CMS1, indomethacin loaded B-CMS2 and indomethacin loaded B-CMS3. After loading indomethacin into B-CMS carriers, surface area, pore volume and pore diameter of B-CMS carriers were reduced. B-CMS converted crystalline state of indomethacin to amorphous state, leading to the improved indomethacin dissolution. B-CMS1 controlled drug release without burst-release, while B-CMS2 and B-CMS3 released indomethacin faster than B-CMS1, demonstrating that the particle length, the ordered lever of multiple helixes, the curvature degree of helical channels and pore diameter greatly contributed to the release behavior of indomethacin loaded B-CMS. - Highlights: • Chiral mesoporous silica was synthesized using biomimetic method. • pH influenced energetics of self-assembly process of chiral mesoporous silica. • Stirring rate determined the particle length of chiral mesoporous silica. • Controlled release behaviors of chiral mesoporous silica varied based on structures

  12. Magnetic graphene oxide as a carrier for targeted delivery of chemotherapy drugs in cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Ya-Shu [Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Lu, Yu-Jen [Department of Neurosurgery, Chang Gung Memorial Hospital, Kwei-San, Taoyuan 33305, Taiwan, ROC (China); Chen, Jyh-Ping, E-mail: jpchen@mail.cgu.edu.tw [Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Department of Plastic and Reconstructive Surgery and Craniofacial Research Center, Chang Gung Memorial Hospital, Kwei-San, Taoyuan 33305, Taiwan, ROC (China); Graduate Institute of Health Industry and Technology, Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kwei-San, Taoyuan 33302, Taiwan, ROC (China); Department of Materials Engineering, Ming Chi University of Technology, Tai-Shan, New Taipei City 24301, Taiwan, ROC (China)

    2017-04-01

    A magnetic targeted functionalized graphene oxide (GO) complex is constituted as a nanocarrier for targeted delivery and pH-responsive controlled release of chemotherapy drugs to cancer cells. Magnetic graphene oxide (mGO) was prepared by chemical co-precipitation of Fe{sub 3}O{sub 4} magnetic nanoparticles on GO nano-platelets. The mGO was successively modified by chitosan and mPEG-NHS through covalent bindings to synthesize mGOC-PEG. The polyethylene glycol (PEG) moiety is expected to prolong the circulation time of mGO by reducing the reticuloendothelial system clearance. Irinotecan (CPT-11) or doxorubicin (DOX) was loaded to mGOC-PEG through π-π stacking interactions for magnetic targeted delivery of the cancer chemotherapy drug. The best values of loading efficiency and loading content of CPT-11 were 54% and 2.7% respectively; whereas for DOX, they were 65% and 393% The pH-dependent drug release profile was further experimented at different pHs, in which ~60% of DOX was released at pH 5.4 and ~10% was released at pH 7.4. In contrast, ~90% CPT-11 was released at pH 5.4 and ~70% at pH 7.4. Based on the drug loading and release characteristics, mGOC-PEG/DOX was further chosen for in vitro cytotoxicity tests against U87 human glioblastoma cell line. The IC50 value of mGOC-PEG/DOX was found to be similar to that of free DOX but was reduced dramatically when subject to magnetic targeting. It is concluded that with the high drug loading and pH-dependent drug release properties, mGOC-PEG will be a promising drug carrier for targeted delivery of chemotherapy drugs in cancer therapy. - Highlights: • mGO was prepared by chemical co-precipitation of Fe{sub 3}O{sub 4} MNP on GO nano-platelets. • mGO was further modified by chitosan and mPEG-NHS to synthesize mGOC-PEG. • mGOC-PEG showed higher drug loading of doxorubicin (DOX) than irinotecan. • mGOC-PEG showed pH-responsive controlled release of chemotherapy drugs. • Magnetic targeting enhanced cytotoxicity of

  13. Magnetic graphene oxide as a carrier for targeted delivery of chemotherapy drugs in cancer therapy

    International Nuclear Information System (INIS)

    Huang, Ya-Shu; Lu, Yu-Jen; Chen, Jyh-Ping

    2017-01-01

    A magnetic targeted functionalized graphene oxide (GO) complex is constituted as a nanocarrier for targeted delivery and pH-responsive controlled release of chemotherapy drugs to cancer cells. Magnetic graphene oxide (mGO) was prepared by chemical co-precipitation of Fe 3 O 4 magnetic nanoparticles on GO nano-platelets. The mGO was successively modified by chitosan and mPEG-NHS through covalent bindings to synthesize mGOC-PEG. The polyethylene glycol (PEG) moiety is expected to prolong the circulation time of mGO by reducing the reticuloendothelial system clearance. Irinotecan (CPT-11) or doxorubicin (DOX) was loaded to mGOC-PEG through π-π stacking interactions for magnetic targeted delivery of the cancer chemotherapy drug. The best values of loading efficiency and loading content of CPT-11 were 54% and 2.7% respectively; whereas for DOX, they were 65% and 393% The pH-dependent drug release profile was further experimented at different pHs, in which ~60% of DOX was released at pH 5.4 and ~10% was released at pH 7.4. In contrast, ~90% CPT-11 was released at pH 5.4 and ~70% at pH 7.4. Based on the drug loading and release characteristics, mGOC-PEG/DOX was further chosen for in vitro cytotoxicity tests against U87 human glioblastoma cell line. The IC50 value of mGOC-PEG/DOX was found to be similar to that of free DOX but was reduced dramatically when subject to magnetic targeting. It is concluded that with the high drug loading and pH-dependent drug release properties, mGOC-PEG will be a promising drug carrier for targeted delivery of chemotherapy drugs in cancer therapy. - Highlights: • mGO was prepared by chemical co-precipitation of Fe 3 O 4 MNP on GO nano-platelets. • mGO was further modified by chitosan and mPEG-NHS to synthesize mGOC-PEG. • mGOC-PEG showed higher drug loading of doxorubicin (DOX) than irinotecan. • mGOC-PEG showed pH-responsive controlled release of chemotherapy drugs. • Magnetic targeting enhanced cytotoxicity of m

  14. Evaluation of the physicochemical properties of liposomes as potential carriers of anticancer drugs: spectroscopic study

    International Nuclear Information System (INIS)

    Pentak, Danuta

    2016-01-01

    Vesicle size and composition are a critical parameter for determining the circulation half-life of liposomes. Size influences the degree of drug encapsulation in liposomes. The geometry, size, and properties of liposomes in an aqueous environment have to be described to enable potential applications of liposome systems as drug carriers. The characteristics of multiple thermotropic phase transitions are also an important consideration in liposomes used for analytical and bioanalytical purposes. The aim of this study was to evaluate the physicochemical properties of liposomes which accommodate hydrophilic and amphiphilic drugs used in cancer therapy. The studied liposomes were prepared with the involvement of the modified reverse-phase evaporation method (mREV). The prepared liposomes had a diameter of 70–150 nm. The analyzed compounds were 1-β-d-arabinofuranosylcytosine, cyclophosphamide, and ifosfamide. In literature, there is no information about simultaneous incorporation of cytarabine, ifosfamide, and cyclophosphamide, in spite of the fact that these drugs have been used for more than 30 years. A combination of the examined drugs is used in CODOX-M/IVAC therapy. CODOX-M/IVAC (cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine) is one of the currently preferred intensive-dose chemotherapy regimens for Burkitt lymphoma (BL). The present research demonstrates the pioneering studies of incorporation of ifosfamide into liposome vesicles, location of and competition between the analyzed drugs and liposome vesicles. The applied methods were nuclear magnetic resonance (NMR), atomic force microscopy (AFM), differential scanning calorimetry (DSC).Graphical Abstract.

  15. Evaluation of the physicochemical properties of liposomes as potential carriers of anticancer drugs: spectroscopic study

    Energy Technology Data Exchange (ETDEWEB)

    Pentak, Danuta, E-mail: danuta.pentak@us.edu.pl [University of Silesia, Department of Materials Chemistry and Chemical Technology, Institute of Chemistry (Poland)

    2016-05-15

    Vesicle size and composition are a critical parameter for determining the circulation half-life of liposomes. Size influences the degree of drug encapsulation in liposomes. The geometry, size, and properties of liposomes in an aqueous environment have to be described to enable potential applications of liposome systems as drug carriers. The characteristics of multiple thermotropic phase transitions are also an important consideration in liposomes used for analytical and bioanalytical purposes. The aim of this study was to evaluate the physicochemical properties of liposomes which accommodate hydrophilic and amphiphilic drugs used in cancer therapy. The studied liposomes were prepared with the involvement of the modified reverse-phase evaporation method (mREV). The prepared liposomes had a diameter of 70–150 nm. The analyzed compounds were 1-β-d-arabinofuranosylcytosine, cyclophosphamide, and ifosfamide. In literature, there is no information about simultaneous incorporation of cytarabine, ifosfamide, and cyclophosphamide, in spite of the fact that these drugs have been used for more than 30 years. A combination of the examined drugs is used in CODOX-M/IVAC therapy. CODOX-M/IVAC (cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine) is one of the currently preferred intensive-dose chemotherapy regimens for Burkitt lymphoma (BL). The present research demonstrates the pioneering studies of incorporation of ifosfamide into liposome vesicles, location of and competition between the analyzed drugs and liposome vesicles. The applied methods were nuclear magnetic resonance (NMR), atomic force microscopy (AFM), differential scanning calorimetry (DSC).Graphical Abstract.

  16. Synthesis and characterization of Zinc (II)-loaded Zeolite/Graphene oxide nanocomposite as a new drug carrier

    International Nuclear Information System (INIS)

    Khatamian, M.; Divband, B.; Farahmand-zahed, F.

    2016-01-01

    Current research has focused on the preparation of Zinc-clinoptilolite/Graphene Oxide (Zn-Clin/GO) hybrid nanostructure and investigating its biocompatibility for the first time. As prepared samples were characterized by X-ray diffraction (XRD), Scanning electron microscopy (SEM), Thermo gravimetric analysis (TGA) and Fourier transform infrared (FT-IR). In order to use it as a drug carrier two important factors were investigated: cytocompatibility of nanocomposites and their drug loading capacity. The results showed that the prepared nanocomposite is cytocompatible and its high loading capacity and slow release performance for Doxorubicin (DOX), as a cancer drug, proved that it can be used as a drug carrier. At last in-vitro toxicity of DOX loaded nanocomposite was compared with pure DOX. - Graphical abstract: Biocompatible Zn-clinoptilolite/Graphene oxide hybrid nanostructure as in vitro drug delivery systems (DDS) was able to store and release substantial amounts of doxorubicin to the lung cancer cell lines. Display Omitted - Highlights: • Zn-Clin/GO nanocomposite as a new in vitro drug carrier with high loading capacity is synthesized. • Two synthesis methods (Microwave assisted hydrothermal method and Reflux method) are used. • All of the carriers (Zn-Clin, Zn-Clin/GO, GO) showed high biocompatibility.

  17. Synthesis and characterization of Zinc (II)-loaded Zeolite/Graphene oxide nanocomposite as a new drug carrier

    Energy Technology Data Exchange (ETDEWEB)

    Khatamian, M. [Inorganic Chemistry Department, Faculty of Chemistry, University of Tabriz, C.P. 51664 Tabriz (Iran, Islamic Republic of); Divband, B., E-mail: baharakdivband@yahoo.com [Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz (Iran, Islamic Republic of); Inorganic Chemistry Department, Faculty of Chemistry, University of Tabriz, C.P. 51664 Tabriz (Iran, Islamic Republic of); Farahmand-zahed, F. [Inorganic Chemistry Department, Faculty of Chemistry, University of Tabriz, C.P. 51664 Tabriz (Iran, Islamic Republic of)

    2016-09-01

    Current research has focused on the preparation of Zinc-clinoptilolite/Graphene Oxide (Zn-Clin/GO) hybrid nanostructure and investigating its biocompatibility for the first time. As prepared samples were characterized by X-ray diffraction (XRD), Scanning electron microscopy (SEM), Thermo gravimetric analysis (TGA) and Fourier transform infrared (FT-IR). In order to use it as a drug carrier two important factors were investigated: cytocompatibility of nanocomposites and their drug loading capacity. The results showed that the prepared nanocomposite is cytocompatible and its high loading capacity and slow release performance for Doxorubicin (DOX), as a cancer drug, proved that it can be used as a drug carrier. At last in-vitro toxicity of DOX loaded nanocomposite was compared with pure DOX. - Graphical abstract: Biocompatible Zn-clinoptilolite/Graphene oxide hybrid nanostructure as in vitro drug delivery systems (DDS) was able to store and release substantial amounts of doxorubicin to the lung cancer cell lines. Display Omitted - Highlights: • Zn-Clin/GO nanocomposite as a new in vitro drug carrier with high loading capacity is synthesized. • Two synthesis methods (Microwave assisted hydrothermal method and Reflux method) are used. • All of the carriers (Zn-Clin, Zn-Clin/GO, GO) showed high biocompatibility.

  18. Investigating the Effects of Loading Factors on the In Vitro Pharmaceutical Performance of Mesoporous Materials as Drug Carriers for Ibuprofen

    Directory of Open Access Journals (Sweden)

    Junmin Lai

    2017-02-01

    Full Text Available The aim of the study was to investigate the effects of the loading factors, i.e., the initial drug loading concentration and the ratio of the drug to carriers, on the in vitro pharmaceutical performance of drug-loaded mesoporous systems. Ibuprofen (IBU was used as a model drug, and two non-ordered mesoporous materials of commercial silica Syloid® 244FP (S244FP and Neusilin® US2 (NS2 were selected in the study. The IBU-loaded mesoporous samples were prepared by a solvent immersion method with a rotary evaporation drying technique and characterized by polarized light microscopy (PLM, Fourier transform infrared (FTIR spectroscopy, X-ray powder diffraction (XRPD and differential scanning calorimetry (DSC. Dissolution experiments were performed in simulated gastric media at 37 °C under non-sink conditions. The concentration of IBU in solution was determined by HPLC. The study showed that the dissolution rate of IBU can be improved significantly using the mesoporous S224FP carriers due to the conversion of crystalline IBU into the amorphous form. Both of the loading factors affected the IBU dissolution kinetics. Due to the molecular interaction between the IBU and NS2 carriers, the loading factors had little effects on the drug release kinetics with incomplete drug desorption recovery and insignificant dissolution enhancement. Care and extensive evaluation must therefore be taken when mesoporous materials are chosen as carrier delivery systems.

  19. Fabrication and characterization of size-controlled starch-based nanoparticles as hydrophobic drug carriers.

    Science.gov (United States)

    Han, Fei; Gao, Chunmei; Liu, Mingzhu

    2013-10-01

    Acetylated corn starch was successfully synthesized and optimized by the reaction of native corn starch with acetic anhydride and acetic acid in the presence of sulfuric acid as a catalyst. The optimal degree of substitution of 2.85 was obtained. Starch-based nanoparticles were fabricated by a simple and novel nanoprecipitation procedure, by the dropwise addition of water to acetone solution of acetylated starch under stirring. Fourier transform infrared spectrometry showed that acetylated starch had some new bands at 1750, 1375 and 1240 cm(-1) while acetylated starch nanoparticles presented the identical peaks as the drug-loaded acetylated starch nanoparticles and the acetylated starch. Wide angle X-ray diffraction indicated that A-type pattern of native starch was completely transformed into the V-type pattern of Acetylated starch and starch-based nanoparticles show the similar type pattern with the acetylated starch. The scanning electron microscopy showed that the different sizes of pores formed on the acetylated starch granules were utterly converted into the uniform-sized spherical nanoparticles after the nanoprecipitation. The encapsulation efficiency and diameter of nanoparticle can be adjusted by the degree of substitution, the volume ratio of nonsolvent to solvent and the weight ratio of acetylated starch to drug. It was also depicted that the release behaviors of drug-loaded nanoparticles depend on the size of nanoparticles and the degree of substitution of the acetylated starch. Release studies prove that the starch-based nanoparticles with uniform size can be used for the encapsulation of hydrophobic drug and attained the sustained and controllable drug release carriers.

  20. Manipulation of magnetic carriers for drug delivery using pulsed-current high T {sub c} superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Yung [Energy Technology Division and Material Science Division, Building 335, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States)]. E-mail: yscha@anl.gov; Chen, Lihua [Energy Technology Division and Material Science Division, Building 335, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States); Department of Electrical and Computer Engineering, Michigan State University, East Lansing, MI 48824 (United States); Askew, Thomas [Energy Technology Division and Material Science Division, Building 335, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States); Physics Department, Kalamazoo College, Kalamazoo, MI 49006 (United States); Veal, Boyd [Energy Technology Division and Material Science Division, Building 335, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States); Hull, John [Energy Technology Division and Material Science Division, Building 335, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States)

    2007-04-15

    An innovative method of manipulating magnetic carriers is proposed, and its feasibility for drug delivery and therapy is demonstrated experimentally. The proposed method employs pulsed-field solenoid coils with high-critical- temperature (T {sub c}) superconductor inserts. Pulsed current is used to magnetize and de-magnetize the superconductor insert. The proposed method was demonstrated to be able to (1) move magnetic particles, ranging in size from a few millimeters to 10 {mu}m, with strong enough forces over a substantial distance, (2) hold the particles at a designated position as long as needed, and (3) reverse the processes and retrieve the particles. We further demonstrated that magnetic particles can be manipulated in a stationary environment, in water flow, and in simulated blood (water/glycerol mixture) flow.

  1. Novel drug delivery carrier from alginate-carrageenan and glycerol as plasticizer

    Science.gov (United States)

    Darmokoesoemo, Handoko; Pudjiastuti, Pratiwi; Rahmatullah, Bagus; Kusuma, Heri Septya

    Drug delivery carriers are materials that can be used to administer drugs into the human body. Alginate and carrageenan are natural polymers that have potential as drug delivery material. Therefore in this study conducted a new innovation using carrageenan and alginates from extract of red seaweed and brown seaweed as base materials of capsule. This is expected to improve the quality of the used materials so it's easier to obtain the capsule with base material from carrageenan-alginate that has good quality as drug delivery carrier. Moreover, in the manufacture of capsules from carrageenan and alginates also added plasticizers in order to maintain the elasticity and the swelling degree of the capsules are made so that the capsules are not brittle. In addition, in this study used glycerol because it is a useful plasticizer to increase the plasticity of a material by filling the cavities between monomers. The capsules were prepared with four variations of glycerol concentration are A, B, C and D. In these capsule was analyzed of surface morphology with SEM, test of swelling degree and test of dissolution kinetics for some acidity level. Analysis of surface morphology with SEM shows that the capsule shell has very small pores. The average of swelling degree for capsules A, B, C and D are 452.4%, 599.0%, 730.66% and 731.25%, respectively. FTIR analysis shows that the presence of glycerol can increase the number of hydrogen bonds that are formed. The acidity level affects the dissolution profile of each capsules. In general with an increasingly alkaline environment causes all the capsules will be easier to release. This is because the increasing of acidic groups in the copolymer causes the capsule to be more easily occur neutralization reaction in a more alkaline environment so that the disintegration of capsules can occur more quickly. In addition from this study also can be seen that the increasing concentration of glycerol can cause the rate of capsule dissolution

  2. Hydrogen-bonding layer-by-layer-assembled biodegradable polymeric micelles as drug delivery vehicles from surfaces.

    Science.gov (United States)

    Kim, Byeong-Su; Park, Sang Wook; Hammond, Paula T

    2008-02-01

    We present the integration of amphiphilic block copolymer micelles as nanometer-sized vehicles for hydrophobic drugs within layer-by-layer (LbL) films using alternating hydrogen bond interactions as the driving force for assembly for the first time, thus enabling the incorporation of drugs and pH-sensitive release. The film was constructed based on the hydrogen bonding between poly(acrylic acid) (PAA) as an H-bond donor and biodegradable poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) micelles as the H-bond acceptor when assembled under acidic conditions. By taking advantage of the weak interactions of the hydrogen-bonded film on hydrophobic surfaces, it is possible to generate flexible free-standing films of these materials. A free-standing micelle LbL film of (PEO-b-PCL/PAA)60 with a thickness of 3.1 microm was isolated, allowing further characterization of the bulk film properties, including morphology and phase transitions, using transmission electron microscopy and differential scanning calorimetry. Because of the sensitive nature of the hydrogen bonding employed to build the multilayers, the film can be rapidly deconstructed to release micelles upon exposure to physiological conditions. However, we could also successfully control the rate of film deconstruction by cross-linking carboxylic acid groups in PAA through thermally induced anhydride linkages, which retard the drug release to the surrounding medium to enable sustained release over multiple days. To demonstrate efficacy in delivering active therapeutics, in vitro Kirby-Bauer assays against Staphylococcus aureus were used to illustrate that the drug-loaded micelle LbL film can release significant amounts of an active antibacterial drug, triclosan, to inhibit the growth of bacteria. Because the micellar encapsulation of hydrophobic therapeutics does not require specific chemical interactions, we believe this noncovalent approach provides a new route to integrating active small

  3. Safety and efficacy of biodegradable drug-eluting vs. bare metal stents: a meta-analysis from randomized trials.

    Science.gov (United States)

    Yin, Yangguang; Zhang, Yao; Zhao, Xiaohui

    2014-01-01

    Biodegradable polymeric coatings have been proposed as a promising strategy to enhance biocompatibility and improve the delayed healing in the vessel. However, the efficacy and safety of biodegradable polymer drug-eluting stents (BP-DES) vs. bare metal stents (BMS) are unknown. The aim of this study was to perform a meta-analysis of randomized controlled trials (RCTs) comparing the outcomes of BP-DES vs. BMS. PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials, until December 2013, that compared any of approved BP-DES and BMS. Efficacy endpoints were target-vessel revascularization (TVR), target-lesion revascularization (TLR) and in-stent late loss (ISLL). Safety endpoints were death, myocardial infarction (MI), definite stent thrombosis (DST). The meta-analysis included 7 RCTs with 2,409 patients. As compared with BMS, there was a significantly reduced TVR (OR [95% CI] = 0.37 [0.28-0.50]), ISLL (OR [95% CI] = -0.41 [-0.48-0.34]) and TLR (OR [95% CI] = 0.38 [0.27-0.52]) in BP-DES patients. However, there were no difference for safety outcomes between BP-DES and BMS. BP-DES is more effective in reducing ISLL, TVR and TLR, as safe as standard BMS with regard to death, ST and MI. Further large RCTs with long-term follow-up are warranted to better define the relative merits of BP-DES.

  4. “Smart” Drug Carriers: PEGylated TATp-Modified pH-Sensitive Liposomes

    Science.gov (United States)

    KALE, AMIT A.; TORCHILIN, VLADIMIR P.

    2012-01-01

    To engineer drug carriers capable of spontaneous accumulation in tumors and ischemic areas via the enhanced permeability and retention (EPR) effect and further penetration and drug delivery inside tumor or ischemic cells via the action of the cell-penetrating peptide (CPP), we have prepared liposomes simultaneously bearing on their surface CPP (TAT peptide, TATp) moieties and protective PEG chains. PEG chains were incorporated into the liposome membrane via the PEG-attached phosphatidylethanolamine (PE) residue with PEG and PE being conjugated with the lowered pH-degradable hydrazone bond (PEG-HZ-PE). Under normal conditions, liposome-grafted PEG “shielded” liposome-attached TATp moieties since the PEG spacer for TATp attachment (PEG1000) was shorter than protective PEG2000. PEGy-lated liposomes are expected to accumulate in targets via the EPR effect, but inside the “acidified” tumor or ischemic tissues lose their PEG coating due to the lowered pH-induced hydrolysis of HZ and penetrate inside cells via the now-exposed TATp moieties. This concept is shown here to work in cell cultures in vitro as well as in ischemic cardiac tissues in the Langendorff perfused rat heart model and in tumors in experimental mice in vivo. PMID:18027240

  5. "Smart" drug carriers: PEGylated TATp-modified pH-sensitive liposomes.

    Science.gov (United States)

    Kale, Amit A; Torchilin, Vladimir P

    2007-01-01

    To engineer drug carriers capable of spontaneous accumulation in tumors and ischemic areas via the enhanced permeability and retention (EPR) effect and further penetration and drug delivery inside tumor or ischemic cells via the action of the cell-penetrating peptide (CPP), we have prepared liposomes simultaneously bearing on their surface CPP (TAT peptide, TATp) moieties and protective PEG chains. PEG chains were incorporated into the liposome membrane via the PEG-attached phosphatidylethanolamine (PE) residue with PEG and PE being conjugated with the lowered pH-degradable hydrazone bond (PEG-HZ-PE). Under normal conditions, liposome-grafted PEG "shielded" liposome-attached TATp moieties since the PEG spacer for TATp attachment (PEG(1000)) was shorter than protective PEG(2000). PEGylated liposomes are expected to accumulate in targets via the EPR effect, but inside the "acidified" tumor or ischemic tissues lose their PEG coating due to the lowered pH-induced hydrolysis of HZ and penetrate inside cells via the now-exposed TATp moieties. This concept is shown here to work in cell cultures in vitro as well as in ischemic cardiac tissues in the Langendorff perfused rat heart model and in tumors in experimental mice in vivo.

  6. Basic evaluation of typical nanoporous silica nanoparticles in being drug carrier: Structure, wettability and hemolysis.

    Science.gov (United States)

    Li, Jing; Guo, Yingyu

    2017-04-01

    Herein, the present work devoted to study the basic capacity of nanoporous silica nanoparticles in being drug carrier that covered structure, wettability and hemolysis so as to provide crucial evaluation. Typical nanoporous silica nanoparticles that consist of nanoporous silica nanoparticles (NSN), amino modified nanoporous silica nanoparticles (amino-NSN), carboxyl modified nanoporous silica nanoparticles (carboxyl-NSN) and hierachical nanoporous silica nanoparticles (hierachical-NSN) were studied. The results showed that their wettability and hemolysis were closely related to structure and surface modification. Basically, wettability became stronger as the amount of OH on the surface of NSN was higher. Both large nanopores and surface modification can reduce the wettability of NSN. Furthermore, NSN series were safe to be used when they circulated into the blood in low concentration, while if high concentration can not be avoided during administration, high porosity or amino modification of NSN were safer to be considered. It is believed that the basic evaluation of NSN can make contribution in providing scientific instruction for designing drug loaded NSN systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Supercritical Assisted Atomization: Polyvinylpyrrolidone as Carrier for Drugs with Poor Solubility in Water

    Directory of Open Access Journals (Sweden)

    Sara Liparoti

    2013-01-01

    Full Text Available Supercritical assisted atomization (SAA is an efficient technique to produce microparticles and composite microspheres formed by polymers and pharmaceutical compounds. In this work polyvinylpyrrolidone (PVP was proposed as carrier for pharmaceutical compounds that show a poor solubility in water medium. Indeed, this polymer is hydrosoluble and can be generally used to enhance the dissolution rate of hydrophobic compounds when finely dispersed in it. However, it is difficult to obtain coprecipitates with a uniform dispersion of the active molecule using other micronization techniques. The experiments were performed using ethanol as solvent; SAA plant was operated at 40°C and 76 bar in the saturator and 70°C and 1.6 bar in the precipitator. Three different dexamethasone/polymer weight ratios were selected: 1/2, 1/4, and 1/8. Produced composite particles showed a regular, spherical shape and a mean diameter ranging from about 0.8 to 1 μm, depending on the polymer/drug weight ratio. Dissolution analysis demonstrated that microparticles containing a lower drug amount show a higher dissolution rate.

  8. The metabolic fate of the Anti-HIV active drug carrier succinylated human serum albumin after intravenous administration in rats

    NARCIS (Netherlands)

    Swart, P J; Kuipers, M E; Smit, C; Beljaars, L; Ter Wiel, J; Meijer, D K

    The pharmacokinetics and metabolic fate of the intrinsically active (anti-HIV) drug carrier succinylated human serum albumin (Suc-HSA) was studied in rats. Suc-HSA was prepared by derivatizing HSA with 1,4-[C-14]-succinic anhydride, a modification by which all available epsilonNH2-groups in HSA were

  9. Synergistically enhanced selective intracellular uptake of anticancer drug carrier comprising folic acid-conjugated hydrogels containing magnetite nanoparticles

    Science.gov (United States)

    Kim, Haneul; Jo, Ara; Baek, Seulgi; Lim, Daeun; Park, Soon-Yong; Cho, Soo Kyung; Chung, Jin Woong; Yoon, Jinhwan

    2017-01-01

    Targeted drug delivery has long been extensively researched since drug delivery and release at the diseased site with minimum dosage realizes the effective therapy without adverse side effects. In this work, to achieve enhanced intracellular uptake of anticancer drug carriers for efficient chemo-therapy, we have designed targeted multifunctional anticancer drug carrier hydrogels. Temperature-responsive poly(N-isopropylacrylamide) (PNIPAm) hydrogel core containing superparamagnetic magnetite nanoparticles (MNP) were prepared using precipitation polymerization, and further polymerized with amine-functionalized copolymer shell to facilitate the conjugation of targeting ligand. Then, folic acid, specific targeting ligand for cervical cancer cell line (HeLa), was conjugated on the hydrogel surface, yielding the ligand conjugated hybrid hydrogels. We revealed that enhanced intracellular uptake by HeLa cells in vitro was enabled by both magnetic attraction and receptor-mediated endocytosis, which were contributed by MNP and folic acid, respectively. Furthermore, site-specific uptake of the developed carrier was confirmed by incubating with several other cell lines. Based on synergistically enhanced intracellular uptake, efficient cytotoxicity and apoptotic activity of HeLa cells incubated with anticancer drug loaded hybrid hydrogels were successfully achieved. The developed dual-targeted hybrid hydrogels are expected to provide a platform for the next generation intelligent drug delivery systems.

  10. Simulations of magnetic capturing of drug carriers in the brain vascular system

    Energy Technology Data Exchange (ETDEWEB)

    Kenjeres, S., E-mail: S.Kenjeres@tudelft.nl [Department of Multi-Scale Physics, Faculty of Applied Sciences, J.M. Burgerscentre for Fluid Dynamics, Delft University of Technology, Leeghwaterstraat 39, 2628 CB Delft (Netherlands); Righolt, B.W. [Department of Multi-Scale Physics, Faculty of Applied Sciences, J.M. Burgerscentre for Fluid Dynamics, Delft University of Technology, Leeghwaterstraat 39, 2628 CB Delft (Netherlands)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Blood flow and magnetic particles distributions in the brain vascular system simulated. Black-Right-Pointing-Pointer Numerical mesh generated from raw MRI images. Black-Right-Pointing-Pointer Significant increase in local capturing of magnetic particles obtained. Black-Right-Pointing-Pointer Promising technique for localised non-invasive treatment of brain tumours. - Abstract: The present paper reports on numerical simulations of blood flow and magnetic drug carrier distributions in a complex brain vascular system. The blood is represented as a non-Newtonian fluid by the generalised power law. The Lagrangian tracking of the double-layer spherical particles is performed to estimate particle deposition under influence of imposed magnetic field gradients across arterial walls. Two situations are considered: neutral (magnetic field off) and active control (magnetic field on) case. The double-layer spherical particles that mimic a real medical drug are characterised by two characteristic diameters - the outer one and the inner one of the magnetic core. A numerical mesh of the brain vascular system consisting of multi-branching arteries is generated from raw MRI scan images of a patient. The blood is supplied through four main inlet arteries and the entire vascular system includes more than 30 outlets, which are modelled by Murray's law. The no-slip boundary condition is applied for velocity components along the smooth and rigid arterial walls. Numerical simulations revealed detailed insights into blood flow patterns, wall-shear-stress and local particle deposition efficiency along arterial walls. It is demonstrated that magnetically targeted drug delivery significantly increased the particle capturing efficiency in the pre-defined regions. This feature can be potentially useful for localised, non-invasive treatment of brain tumours.

  11. Photosensitizer-mediated mitochondria-targeting nanosized drug carriers: Subcellular targeting, therapeutic, and imaging potentials.

    Science.gov (United States)

    Choi, Yeon Su; Kwon, Kiyoon; Yoon, Kwonhyeok; Huh, Kang Moo; Kang, Han Chang

    2017-03-30

    Mitochondria-targeting drug carriers have considerable potential because of the presence of many molecular drug targets in the mitochondria and their pivotal roles in cellular viability, metabolism, maintenance, and death. To compare the mitochondria-targeting abilities of triphenylphosphonium (TPP) and pheophorbide a (PhA) in nanoparticles (NPs), this study prepared mitochondria-targeting NPs using mixtures of methoxy poly(ethylene glycol)-(SS-PhA) 2 [mPEG-(SS-PhA) 2 or PPA] and TPP-b-poly(ε-caprolactone)-b-TPP [TPP-b-PCL-b-TPP or TPCL], which were designated PPA n -TPCL 4-n (0≤n≤4) NPs. With increasing TPCL content, the formed PPA n -TPCL 4-n NPs decreased in size from 33nm to 18nm and increased in terms of positive zeta-potentials from -12mV to 33mV. Although the increased TPCL content caused some dark toxicity of the PPA n -TPCL 4-n NPs due to the intrinsic positive character of TPCL, the NPs showed strong light-induced killing effects in tumor cells. In addition, the mitochondrial distribution of the PPA n -TPCL 4-n NPs was analyzed and imaged by flow cytometry and confocal microscopy, respectively. Thus, the PhA-containing NPs specifically targeted the mitochondria, and light stimulation caused PhA-mediated therapeutic effects and imaging functions. Expanding the capabilities of these nanocarriers by incorporating other drugs should enable multiple potential applications (e.g., targeting, therapy, and imaging) for combination and synergistic treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Multiple targeted drugs carrying biodegradable membrane barrier: anti-adhesion, hemostasis, and anti-infection.

    Science.gov (United States)

    Wang, Heran; Li, Min; Hu, Jianming; Wang, Chenhong; Xu, Shanshan; Han, Charles C

    2013-04-08

    A multiple targeted drug carrying bilayer membrane for preventing an abdominal adhesion is prepared by electrospinning. Two bioactive drugs were successfully incorporated into this bilayer membrane and can be independently released from nanofibrous scaffolds without losing structural integrity and functionality of the anti-adhesion membrane. Besides, the drug release profile could be easily adjusted by optimizing the swelling behavior of the fibrous scaffold. The inner layer of the bilayered fibrous membranes loaded with carbazochrome sodium sulfonate (CA) showed an excellent vascular hemostatic efficacy and formed little clot during in vivo experiment. The outer layer loaded with tinidazole (TI) had outstanding antibacterial effect against the anaerobe. We believe this approach could serve as a model technique to guide the design of implants with drug delivery functions.

  13. Biodegradable cationic polymeric nanocapsules for overcoming multidrug resistance and enabling drug-gene co-delivery to cancer cells

    Science.gov (United States)

    Chen, Chih-Kuang; Law, Wing-Cheung; Aalinkeel, Ravikumar; Yu, Yun; Nair, Bindukumar; Wu, Jincheng; Mahajan, Supriya; Reynolds, Jessica L.; Li, Yukun; Lai, Cheng Kee; Tzanakakis, Emmanuel S.; Schwartz, Stanley A.; Prasad, Paras N.; Cheng, Chong

    2014-01-01

    Having unique architectural features, cationic polymeric nanocapsules (NCs) with well-defined covalently stabilized biodegradable structures were generated as potentially universal and safe therapeutic nanocarriers. These NCs were synthesized from allyl-functionalized cationic polylactide (CPLA) by highly efficient UV-induced thiol-ene interfacial cross-linking in transparent miniemulsions. With tunable nanoscopic sizes, negligible cytotoxicity and remarkable degradability, they are able to encapsulate doxorubicin (Dox) with inner cavities and bind interleukin-8 (IL-8) small interfering RNA (siRNA) with cationic shells. The Dox-encapsulated NCs can effectively bypass the P-glycoprotein (Pgp)-mediated multidrug resistance of MCF7/ADR cancer cells, thereby resulting in increased intracellular drug concentration and reduced cell viability. In vitro studies also showed that the NCs loaded with Dox, IL-8 siRNA and both agents can be readily taken up by PC3 prostate cancer cells, resulting in a significant chemotherapeutic effect and/or IL-8 gene silencing.Having unique architectural features, cationic polymeric nanocapsules (NCs) with well-defined covalently stabilized biodegradable structures were generated as potentially universal and safe therapeutic nanocarriers. These NCs were synthesized from allyl-functionalized cationic polylactide (CPLA) by highly efficient UV-induced thiol-ene interfacial cross-linking in transparent miniemulsions. With tunable nanoscopic sizes, negligible cytotoxicity and remarkable degradability, they are able to encapsulate doxorubicin (Dox) with inner cavities and bind interleukin-8 (IL-8) small interfering RNA (siRNA) with cationic shells. The Dox-encapsulated NCs can effectively bypass the P-glycoprotein (Pgp)-mediated multidrug resistance of MCF7/ADR cancer cells, thereby resulting in increased intracellular drug concentration and reduced cell viability. In vitro studies also showed that the NCs loaded with Dox, IL-8 siRNA and both

  14. Efficacy and safety of biodegradable polymer biolimus-eluting stents versus durable polymer drug-eluting stents: a meta-analysis.

    Science.gov (United States)

    Ye, Yicong; Xie, Hongzhi; Zeng, Yong; Zhao, Xiliang; Tian, Zhuang; Zhang, Shuyang

    2013-01-01

    Drug-eluting stents (DES) with biodegradable polymers have been developed to address the risk of thrombosis associated with first-generation DES. We aimed to determine the efficacy and safety of biodegradable polymer biolimus-eluting stents (BES) versus durable polymer DES. Systematic database searches of MEDLINE (1950 to June 2013), EMBASE (1966 to June 2013), the Cochrane Central Register of Controlled Trials (Issue 6 of 12, June 2013), and a review of related literature were conducted. All randomized controlled trials comparing biodegradable polymer BES versus durable polymer DES were included. Eight randomized controlled trials investigating 11,015 patients undergoing percutaneous coronary interventions were included in the meta-analysis. The risk of major adverse cardiac events did not differ significantly between the patients treated with the biodegradable polymer BES and the durable polymer DES (Relative risk [RR], 0.970; 95% CI, 0.848-1.111; p = 0.662). However, biodegradable polymer BES was associated with reduced risk of very late ST compared with the durable polymer DES, while the risk of early or late ST was similar (RR for early or late ST, 1.167; 95% CI 0.755-1.802; p = 0.487; RR 0.273; 95% CI 0.115-0.652; p = 0.003; p for interaction = 0.003). In this meta-analysis of randomized controlled trials, treatments with biodegradable polymer BES did not significantly reduce the risk of major adverse cardiac events, but demonstrated a significantly lower risk of very late ST when compared to durable polymer DES. This conclusion requires confirmation by further studies with long-term follow-up. http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013004364#.UnM2lfmsj6J.

  15. Efficacy and safety of biodegradable polymer biolimus-eluting stents versus durable polymer drug-eluting stents: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yicong Ye

    Full Text Available BACKGROUNDS: Drug-eluting stents (DES with biodegradable polymers have been developed to address the risk of thrombosis associated with first-generation DES. We aimed to determine the efficacy and safety of biodegradable polymer biolimus-eluting stents (BES versus durable polymer DES. METHODS: Systematic database searches of MEDLINE (1950 to June 2013, EMBASE (1966 to June 2013, the Cochrane Central Register of Controlled Trials (Issue 6 of 12, June 2013, and a review of related literature were conducted. All randomized controlled trials comparing biodegradable polymer BES versus durable polymer DES were included. RESULTS: Eight randomized controlled trials investigating 11,015 patients undergoing percutaneous coronary interventions were included in the meta-analysis. The risk of major adverse cardiac events did not differ significantly between the patients treated with the biodegradable polymer BES and the durable polymer DES (Relative risk [RR], 0.970; 95% CI, 0.848-1.111; p = 0.662. However, biodegradable polymer BES was associated with reduced risk of very late ST compared with the durable polymer DES, while the risk of early or late ST was similar (RR for early or late ST, 1.167; 95% CI 0.755-1.802; p = 0.487; RR 0.273; 95% CI 0.115-0.652; p = 0.003; p for interaction = 0.003. CONCLUSIONS: In this meta-analysis of randomized controlled trials, treatments with biodegradable polymer BES did not significantly reduce the risk of major adverse cardiac events, but demonstrated a significantly lower risk of very late ST when compared to durable polymer DES. This conclusion requires confirmation by further studies with long-term follow-up. PROSPERO REGISTER NUMBER: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013004364#.UnM2lfmsj6J.

  16. Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

    Science.gov (United States)

    Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2016-06-01

    From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

  17. Crosslinked hydrogels—a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs

    Directory of Open Access Journals (Sweden)

    Dajun D. Sun

    2014-02-01

    Full Text Available Water-insoluble materials containing amorphous solid dispersions (ASD are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate (PHEMA can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.

  18. Hot embossing and mechanical punching of biodegradable microcontainers for oral drug delivery

    DEFF Research Database (Denmark)

    Petersen, Ritika Singh; Mahshid, Rasoul; Andersen, Nis Korsgaard

    2015-01-01

    A process has been developed to fabricate discrete three-dimensional microcontainers for oral drug delivery application in Poly-L-Lactic Acid (PLLA) polymer. The method combines hot embossing for the definition of holes in a PLLA film and mechanical punching to penetrate the polymer layer around...... the holes, after filling them with drug. Here, we demonstrate the fabrication of microcontainers with a diameter of 340 lm and a height of 50 lm. The process is temperature benign so that the compositional integrity of the drug is preserved. It also provides a good flexibility for creating different sizes...... and shapes of microcontainers. Finally, the process is compatible with roll-to-roll processing that could lead to low cost high volume production. © 2014 Elsevier B.V. All rights reserved....

  19. INVESTIGATION OF DRUG RELEASE FROM BIODEGRADABLE PLG MICROSPHERES: EXPERIMENT AND THEORY

    Energy Technology Data Exchange (ETDEWEB)

    ANDREWS, MALCOLM J. [Los Alamos National Laboratory; BERCHANE, NADER S. [Los Alamos National Laboratory; CARSON, KENNETH H. [Los Alamos National Laboratory; RICE-FICHT, ALLISON C. [Los Alamos National Laboratory

    2007-01-30

    Piroxicam containing PLG microspheres having different size distributions were fabricated, and in vitro release kinetics were determined for each preparation. Based on the experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the system size was increased. The mathematical model gave a good fit to the experimental release data.

  20. Late clinical outcomes after implantation of drug-eluting stents coated with biodegradable polymers: 3-year follow-up of the PAINT randomised trial.

    Science.gov (United States)

    Lemos, Pedro A; Moulin, Bruno; Perin, Marco A; Oliveira, Ludmilla A R R; Arruda, J Airton; Lima, Valter C; Lima, Antonio A G; Caramori, Paulo R A; Medeiros, Cesar R; Barbosa, Mauricio R; Brito, Fabio S; Ribeiro, Expedito E

    2012-05-15

    The long-term clinical performance of drug-eluting stents (DES) coated with biodegradable polymers is poorly known. A total of 274 coronary patients were randomly allocated to paclitaxel-eluting stents, sirolimus-eluting stents, or bare metal stents (2:2:1 ratio). The two DES used the same biodegradable polymers and were identical except for the drug. At three years, the pooled DES population had similar rates of cardiac death or myocardial infarction (9.0% vs. 7.1; p=0.6), but lower risk of repeat interventions (10.0% vs. 29.9%; pbiodegradable-polymer coated DES releasing either paclitaxel or sirolimus were effective in reducing the 3-year rate of re-interventions.

  1. 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

  2. Controlled slow release of anticancer drugs from protein-hydrophilic vinyl polymer carriers

    International Nuclear Information System (INIS)

    Asano, Masaharu; Yoshida, Masaru; Kaetsu, Isao

    1982-01-01

    The release behavior has been studied for bleomycin hydrochloride (BLM), an anticancer drug, from carrier composities prepared from mixtures of proteins and hydrophilic vinyl monomers by combined procedures of radiation polymerization and thermal denaturation. The magnitude, Q/tsup(1/2), for BLM release was the smallest when albumin was denatured by thermal treatment after the polymerization of albumin-2-hydroxyethyl methacrylate (HEMA) by radiation at -78 0 C. This retardation was further enhanced by the use of cross-linked polymers. On the other hand, the digestion of the albumin-HEMA composite, during the release test carried out in the saline containing some proteases, was markedly suppressed with increasing the HEMA content in the composite. The digestion was lowered more than expected from the albumin content in the composite. In summary of the release tests and the scanning electron microscopic observations, it was concluded that the release of BLM and the digestion of albumin component contained in the composites can be markedly suppressed by the incorporation of the polymeric component. (author)

  3. Biodegradable polymersomes as carriers and release systems for paclitaxel using Oregon Green® 488 labeled paclitaxel as a model compound

    NARCIS (Netherlands)

    Lee, Jung Seok; Feijen, Jan

    2012-01-01

    Oregon Green® 488 labeled paclitaxel (Flutax) loaded biodegradable polymersomes (Flutax-Ps) based on methoxy poly(ethylene glycol)-b-poly(d,l-lactide) (mPEG-PDLLA), methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) or a mixture of the block copolymers (50:50, w/w) were prepared

  4. Synthesis of biodegradable amphiphilic Y-shaped block co-polymers via ring-opening polymerization for drug delivery.

    Science.gov (United States)

    Jia, Lin; Yan, Lifeng; Li, Yang

    2011-01-01

    A series of novel Y-shaped biodegradable block co-polymers of poly(ε-caprolactone) (PCL) and poly(ethyl ethylene phosphate) (PEEP) (PCL-(PEEP)2) were synthesized via ring-opening polymerization (ROP) of EEP with bis-hydroxy-functional ROP initiator (init-PCL-(OH)2). The init-PCL-(OH)2 was synthesized by ROP of CL using 4-hydroxybutyl acrylate (HBA) as initiator and L-tartaric acid as catalyst in bulk, and subsequently the resulting vinyl-terminated PCL was end-capped by acetyl chloride, followed by Michael addition using excess diethanolamine. The Y-shaped co-polymers and their intermediates were characterized by (1)H-, (13)C-, (31)P-NMR, FT-IR and gel-permeation chromatography. The results indicated that the molecular weight of the Y-shaped co-polymers increased with the increasing of the molar ratios of EEP to init-PCL-(OH)2 in the feed, while the PCL chain length was kept constant. The amphiphilic block co-polymers could self-assemble into micelles in aqueous solution, which was demonstrated by dynamic light scattering, (1)H-NMR and atomic force microscopy. A study of controlled release of indomethacin indicated that the amphiphilic block co-polymers could potentially provide novel vehicles for drug delivery.

  5. Non-biodegradable polymer particles for drug delivery: A new technology for "bio-active" restorative materials.

    Science.gov (United States)

    Imazato, Satoshi; Kitagawa, Haruaki; Tsuboi, Ririko; Kitagawa, Ranna; Thongthai, Pasiree; Sasaki, Jun-Ichi

    2017-09-26

    To develop dental restorative materials with "bio-active" functions, addition of the capability to release active agents is an effective approach. However, such functionality needs to be attained without compromising the basic properties of the restorative materials. We have developed novel non-biodegradable polymer particles for drug delivery, aimed for application in dental resins. The particles are made using 2-hydroxyethyl methacrylate (HEMA) and a cross-linking monomer trimethylolpropane trimethacrylate (TMPT), with a hydrophilic nature to adsorb proteins or water-soluble antimicrobials. The polyHEMA/TMPT particles work as a reservoir to release fibroblast growth factor-2 (FGF-2) or cetylpyridinium chloride (CPC) in an effective manner. Application of the polyHEMA/TMPT particles loaded with FGF-2 to adhesives, or those loaded with CPC to resin-based endodontic sealers or denture bases/crowns is a promising approach to increase the success of the treatments by conferring "bio-active" properties to these materials to induce tissue regeneration or to inhibit bacterial infection.

  6. Biodegradable gelatin-based nanospheres as pH-responsive drug delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Curcio, Manuela; Altimari, Ilaria; Spizzirri, Umile Gianfranco, E-mail: g.spizzirri@unical.it; Cirillo, Giuseppe [University of Calabria, Department of Pharmacy, Health and Nutrition Sciences (Italy); Vittorio, Orazio [NEST Scuola Normale Superiore, Istituto Nanoscienze-CNR (Italy); Puoci, Francesco; Picci, Nevio; Iemma, Francesca [University of Calabria, Department of Pharmacy, Health and Nutrition Sciences (Italy)

    2013-04-15

    Native gelatin, N,N Prime -ethylenebisacrylamide, and sodium methacrylate were inserted into a spherical crosslinked structure by a solvent-free emulsion polymerization method, in which sunflower seed oil containing different amounts of lecithin was selected as continuous phase. Nanogels were characterized by morphological analysis, particle size distribution, and determination of swelling degree. Different dimensional distributions (100-500 nm) and water affinities were obtained by varying the amount of surfactant in the polymerization feed. Nanogels were non-toxic on human bone marrow mesenchymal stromal cells and enzymatically stable in the gastric tract, with weight losses ranging from 58 to 20 % in pancreatin solution. Release profiles of diclofenac sodium salt from the nanogels were evaluated at different pH and found to depend on crosslinking degree and drug-polymer interactions; while in pancreatin solution, a complete release of the drug was observed. The release mechanism and the diffusional contribution were evaluated by semiempirical equations.

  7. Biodegradable gelatin-based nanospheres as pH-responsive drug delivery systems

    Science.gov (United States)

    Curcio, Manuela; Altimari, Ilaria; Spizzirri, Umile Gianfranco; Cirillo, Giuseppe; Vittorio, Orazio; Puoci, Francesco; Picci, Nevio; Iemma, Francesca

    2013-04-01

    Native gelatin, N, N'-ethylenebisacrylamide, and sodium methacrylate were inserted into a spherical crosslinked structure by a solvent-free emulsion polymerization method, in which sunflower seed oil containing different amounts of lecithin was selected as continuous phase. Nanogels were characterized by morphological analysis, particle size distribution, and determination of swelling degree. Different dimensional distributions (100-500 nm) and water affinities were obtained by varying the amount of surfactant in the polymerization feed. Nanogels were non-toxic on human bone marrow mesenchymal stromal cells and enzymatically stable in the gastric tract, with weight losses ranging from 58 to 20 % in pancreatin solution. Release profiles of diclofenac sodium salt from the nanogels were evaluated at different pH and found to depend on crosslinking degree and drug-polymer interactions; while in pancreatin solution, a complete release of the drug was observed. The release mechanism and the diffusional contribution were evaluated by semiempirical equations.

  8. Biodegradable micellar HPMA-based polymer-drug conjugates with betulinic acid for passive tumor targeting

    Czech Academy of Sciences Publication Activity Database

    Lomkova, Ekaterina A.; Chytil, Petr; Janoušková, Olga; Mueller, T.; Lucas, H.; Filippov, Sergey K.; Trhlíková, Olga; Aleshunin, P. A.; Skorik, Y. A.; Ulbrich, Karel; Etrych, Tomáš

    2016-01-01

    Roč. 17, č. 11 (2016), s. 3493-3507 ISSN 1525-7797 R&D Projects: GA MŠk(CZ) LO1507; GA MŠk(CZ) LQ1604; GA ČR(CZ) GA15-02986S Institutional support: RVO:61389013 Keywords : N-(2-hydroxypropyl)methacrylamide (HPMA) * polymeric micelles * drug delivery Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.246, year: 2016

  9. Biodegradable polymer stents vs second generation drug eluting stents: A meta-analysis and systematic review of randomized controlled trials.

    Science.gov (United States)

    Pandya, Bhavi; Gaddam, Sainath; Raza, Muhammad; Asti, Deepak; Nalluri, Nikhil; Vazzana, Thomas; Kandov, Ruben; Lafferty, James

    2016-02-26

    To evaluate the premise, that biodegradable polymer drug eluting stents (BD-DES) could improve clinical outcomes compared to second generation permanent polymer drug eluting stents (PP-DES), we pooled the data from all the available randomized control trials (RCT) comparing the clinical performance of both these stents. A systematic literature search of PubMed, Cochrane, Google scholar databases, EMBASE, MEDLINE and SCOPUS was performed during time period of January 2001 to April 2015 for RCT and comparing safety and efficacy of BD-DES vs second generation PP-DES. The primary outcomes of interest were definite stent thrombosis, target lesion revascularization, myocardial infarction, cardiac deaths and total deaths during the study period. A total of 11 RCT's with a total of 12644 patients were included in the meta-analysis, with 6598 patients in BD-DES vs 6046 patients in second generation PP-DES. The mean follow up period was 16 mo. Pooled analysis showed non-inferiority of BD-DES, comparing events of stent thrombosis (OR = 1.42, 95%CI: 0.79-2.52, P = 0.24), target lesion revascularization (OR = 0.99, 95%CI: 0.84-1.17, P = 0.92), myocardial infarction (OR = 1.06, 95%CI: 0.86-1.29, P = 0.92), cardiac deaths (OR = 1.07, 95%CI 0.82-1.41, P = 0.94) and total deaths (OR = 0.96, 95%CI: 0.80-1.17, P = 0.71). BD-DES, when compared to second generation PP-DES, showed no significant advantage and the outcomes were comparable between both the groups.

  10. Effect of particle size of calcium phosphate based bioceramic drug delivery carrier on the release kinetics of ciprofloxacin hydrochloride: an in vitro study

    Science.gov (United States)

    Sasikumar, Swamiappan

    2013-09-01

    Hydroxyapatite (HAP) is the constituent of calcium phosphate based bone cement and it is extensively used as a bone substitute and drug delivery vehicle in various biomedical applications. In the present study we investigated the release kinetics of ciprofloxacin loaded HAP and analyzed its ability to function as a targeted and sustained release drug carrier. Synthesis of HAP was carried out by combustion method using tartaric acid as a fuel and nitric acid as an oxidizer. Powder XRD and FTIR techniques were employed to characterize the phase purity of the drug carrier and to verify the chemical interaction between the drug and carrier. The synthesized powders were sieve separated to make two different drug carriers with different particle sizes and the surface topography of the pellets of the drug carrier was imaged by AFM. Surface area and porosity of the drug carrier was carried out using surface area analyzer. The in-vitro drug release kinetics was performed in simulated body fluid, at 37.3°C. The amount of ciprofloxacin released is measured using UV-visible spectroscopy following the characteristic λ max of 278 nm. The release saturates around 450 h which indicates that it can be used as a targeted and sustained release carrier for bone infections.

  11. Self-assembled biodegradable amphiphilic PEG-PCL-lPEI triblock copolymers at the borderline between micelles and nanoparticles designed for drug and gene delivery.

    Science.gov (United States)

    Endres, Thomas K; Beck-Broichsitter, Moritz; Samsonova, Olga; Renette, Thomas; Kissel, Thomas H

    2011-10-01

    Amphiphilic PEG-PCL-PEI triblock copolymers self-assemble into nano-scaled, positively charged, multifunctional carriers, suitable for drug and gene delivery. A set of block copolymers with varying hydrophilic/hydrophobic ratio (systematically altered at the borderline of micelle and particle forming polymers) was synthesized, characterized and assembled into carriers. A detailed structural characterization in the liquid state of these assemblies was carried out: carrier size was determined using dynamic light scattering, cryogenic scanning electron microscopy and atomic force microscopy. Nuclear magnetic resonance analyses elucidated carrier's core-shell structure. ζ-potential and thickness of the hydrophilic outer polymer shell were determined by laser Doppler anemometry. Subsequently the impact of carrier's structure on its features (stability and toxicity) was investigated. Polymers hydrophilic in nature formed small (polymers aggregated to larger particle-like assemblies (>100 nm). Monitoring carrier size as a function of initial polymer concentration clarified different assembly mechanisms. Shell thickness, colloidal stability and toxicity were found to depend on the length of the hydrophilic polymer block. Due to controllable size, charge, stability and toxicity, this class of novel carriers is a promising candidate for prospective co-delivery of drugs and nucleic acids. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Biodegradable polymer drug-eluting stents versus second-generation drug-eluting stents for patients with coronary artery disease: an update meta-analysis.

    Science.gov (United States)

    Wang, Yanyu; Dong, Pingshuan; Li, Ling; Li, Xiaoling; Wang, Hongyun; Yang, Xuming; Wang, Shaoxin; Li, Zhuanzhen; Shang, Xiyan

    2014-08-01

    Permanent polymer drug-eluting stents (DES) are associated with a higher risk of late and very late stent thrombosis (ST); biodegradable polymer drug-eluting stents (BP-DES) were designed to reduce these risks. However, their benefits are not completely clear. We undertook a meta-analysis of randomized studies identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. Eligible studies were those that compared BP-DES with second-generation permanent polymer DES in patients undergoing percutaneous coronary intervention. Five studies (8,740 patients) with a mean follow-up of 19.2 months were included. Overall, BP-DES were associated with a broadly equivalent risk of definite and probable ST (odds ratio [OR], 1.07; 95 % confidence interval [CI], 0.67 to 1.71; P = 0.76; I (2) = 5.0 %), target vessel revascularization (OR, 1.04; 95 % CI, 0.87 to 1.24; P = 0.68; I (2) = 38.0 %), all-cause mortality (OR, 1.10; 95 % CI, 0.87 to 1.41; P = 0.42; I (2) = 0.0 %), and major adverse cardiac events (OR, 1.03; 95 % CI, 0.88 to 1.20; P = 0.74; I (2) = 0.0 %) when compared with second-generation DES. However, BP-DES significantly decreased in-stent late luminal loss (standard mean difference [SMD], -0.01; 95 % CI, -0.12 to 0.11; P = 0.93; I (2) = 0.0 %) and in-segment late luminal loss (SMD, -0.06; 95 % CI, -0.17 to 0.05; P = 0.27; I (2) = 0.0 %) compared with second-generation DES. Compared with second-generation permanent polymer DES, biodegradable stents appear to have equivalent short- to medium-term clinical benefits, and it remains unclear whether they reduce the incidence of very late ST.

  13. In situ biodegradable crosslinking of cationic oligomer coating on mesoporous silica nanoparticles for drug delivery.

    Science.gov (United States)

    Wang, Yifeng; Wang, Jine; Yang, Yang; Sun, Yi; Yuan, Yuan; Li, Yulin; Liu, Changsheng

    2017-05-01

    Although layer-by-layer assembly using anionic and cationic polymer has been a popular way to develop core-shell nanoparticles, the strong electrostatic interactions may limit shell degradability, thus hampering their application as a platform for controlled therapeutic delivery. In this study, we demonstrate a simple approach to developing mesoporous nanohybrids via a process of pre-drug loading (using doxorubicin (DOX) as a model drug) into mesoporous silica nanoparticles (MSN), followed by surface functionalization with a kind of cationic oligomer (low molecular weight polyethylene imine, LPEI) and in situ crosslinking by degradable N,N'-bis(acryloyl)cystamine (BAC). The presence of LPEI shell affords the nanohybrids with charge-reversal ability, which means that the acidic tumor extracellular microenvironment can transform the negative surface charge at neutral conditions into positive-charged ones. The nanohybrids displayed a pH- and redox-dual sensitivity in DOX release under conditions that mimic intracellular reductive conditions and acidic tumor microenvironments. The nanohybrids can be effectively internalized into A549 cells (a carcinomic human alveolar basal epithelial cell line), resulting in a high DOX intracellular accumulation and an improved anticancer cytotoxicity when compared with free DOX, suggesting their high potential as a new platform for therapeutic delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Drug-lactose binding aspects in adhesive mixtures: controlling performance in dry powder inhaler formulations by altering lactose carrier surfaces.

    Science.gov (United States)

    Zhou, Qi Tony; Morton, David A V

    2012-03-15

    For dry powder inhaler formulations, micronized drug powders are commonly mixed with coarse lactose carriers to facilitate powder handling during the manufacturing and powder aerosol delivery during patient use. The performance of such dry powder inhaler formulations strongly depends on the balance of cohesive and adhesive forces experienced by the drug particles under stresses induced in the flow environment during aerosolization. Surface modification with appropriate additives has been proposed as a practical and efficient way to alter the inter-particulate forces, thus potentially controlling the formulation performance, and this strategy has been employed in a number of different ways with varying degrees of success. This paper reviews the main strategies and methodologies published on surface coating of lactose carriers, and considers their effectiveness and impact on the performance of dry powder inhaler formulations. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Optimization of biodegradable sponges as controlled release drug matrices. I. Effect of moisture level on chitosan sponge mechanical properties.

    Science.gov (United States)

    Foda, Nagwa H; El-laithy, Hanan M; Tadros, Mina I

    2004-04-01

    Cross-linked chitosan sponges as controlled release drug carrier systems were developed. Tramadol hydrochloride, a centrally acting analgesic, was used as a model drug. The sponges were prepared by freeze-drying 1.25% and 2.5% (w/w) high and low M.wt. chitosan solutions, respectively, using glutaraldehyde as a cross-linking agent. The hardness of the prepared sponges was a function of glutaraldehyde concentration and volume where the optimum concentration that offered accepted sponge consistency was 5%. Below or above 5%, very soft or very hard and brittle sponges were obtained, respectively. The determined drug content in the prepared sponges was uniform and did not deviate markedly from the calculated amount. Scanning electron microscopy (SEM) was used to characterize the internal structures of the sponges. The SEM photos revealed that cross-linked high M.wt. chitosan sponges have larger size surface pores that form connections (channels) with the interior of the sponge than cross-linked low M.wt. ones. Moreover, crystals of the incorporated Tramadol hydrochloride were detected on the lamellae and within pores in both chitosan sponges. Differences in pore size and dissolution medium uptake capacity were crucial factors for the more delayed drug release from cross-linked low M.wt. chitosan sponges over high M.wt. ones at pH 7.4. Kinetic analysis of the release data using linear regression followed the Higuchi diffusion model over 12 hours. Setting storage conditions at room temperature under 80-92% relative humidity resulted in soft, elastic, and compressible sponges.

  16. Passive tumor targeting of polymer therapeutics: in vivo imaging of both the polymer carrier and the enzymatically cleavable drug model

    Czech Academy of Sciences Publication Activity Database

    Pola, Robert; Heinrich, A. K.; Mueller, T.; Kostka, Libor; Mäder, K.; Pechar, Michal; Etrych, Tomáš

    2016-01-01

    Roč. 16, č. 11 (2016), s. 1577-1582 ISSN 1616-5187 R&D Projects: GA ČR(CZ) GA15-02986S; GA ČR(CZ) GA16-17207S; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : polymer drug carriers * tumor targeting * enzymatic release Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.238, year: 2016

  17. Biodegradable gelatin-based nanospheres as pH-responsive drug delivery systems

    International Nuclear Information System (INIS)

    Curcio, Manuela; Altimari, Ilaria; Spizzirri, Umile Gianfranco; Cirillo, Giuseppe; Vittorio, Orazio; Puoci, Francesco; Picci, Nevio; Iemma, Francesca

    2013-01-01

    Native gelatin, N,N′-ethylenebisacrylamide, and sodium methacrylate were inserted into a spherical crosslinked structure by a solvent-free emulsion polymerization method, in which sunflower seed oil containing different amounts of lecithin was selected as continuous phase. Nanogels were characterized by morphological analysis, particle size distribution, and determination of swelling degree. Different dimensional distributions (100–500 nm) and water affinities were obtained by varying the amount of surfactant in the polymerization feed. Nanogels were non-toxic on human bone marrow mesenchymal stromal cells and enzymatically stable in the gastric tract, with weight losses ranging from 58 to 20 % in pancreatin solution. Release profiles of diclofenac sodium salt from the nanogels were evaluated at different pH and found to depend on crosslinking degree and drug–polymer interactions; while in pancreatin solution, a complete release of the drug was observed. The release mechanism and the diffusional contribution were evaluated by semiempirical equations.

  18. Stent selection in patients with myocardial infarction: drug eluting, biodegradable polymers or bare metal stents?

    Science.gov (United States)

    Mieres, Juan; Rodríguez, Alfredo E

    2012-08-01

    Percutaneous coronary intervention (PCI) has been increasingly used in the last years during interventional procedures in patients with acute coronary syndromes (ACS) including ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). In patients with either STEMI, NSTEMI, high risk ACS with EKG changes or cardiac enzymes rises; PCI with bare metal stent (BMS) implantation has been associated with a significant improvement in clinical outcome. Therefore, BMS implantation during primary PCI in STEMI has become a standard of practice. With the introduction of drug eluting stents (DESs) in this decade, the use of these new devices instead of BMSs in patients with STEMI has emerged as a rational PCI alternative in this particular subgroup of patients. In spite of the unquestionable benefits of DESs in terms of reduction of restenosis and TVR, specific concerns have arisen with regard to their long-term safety. High incidence of very late stent thrombosis has been described with these devices, and special attention should be paid in patients with unstable coronary lesions, in which plaque composition and remodeling may play a main role in their safety and long-term outcome. Intraluminal thrombus caused by plaque rupture is the most frequent mechanism of STEMI, in which the necrotic core and thin fibrous cap play a major role. In this context, the use of first DESs designs may be futile or even unsafe because delayed healing may further contribute to plaque instability. Adjunctive invasive imaging tools can improve stent deployment and safety outcome in these lesions with intravascular findings of plaque instability. Recently, other players such as new dedicated antithrombotic BMS designs, including selfexpanding stents or drug-eluting coated balloons, are exploring their potential indications in patients with ACS and myocardial infarction. This paper reports and discusses new stent devices and adjunctive pharmacologic agents. It

  19. Characterization of different vitamin E carriers intended for pulmonary drug delivery.

    Science.gov (United States)

    Laouini, A; Andrieu, V; Vecellio, L; Fessi, H; Charcosset, C

    2014-08-25

    The targeted release of drugs intended for pulmonary delivery is a research field which has been so far rather unexploited but is currently becoming increasingly attractive. Liquid dispersions encapsulating vitamin E (liposomes, micelles, nano-emulsion, and solid lipid particles) were prepared using various methods based on membrane contactor. The dispersions were nebulized and aerodynamic characteristics of the generated aerosols were assessed using two different methods: laser light scattering and cascade impaction. When the laser diffraction technique was used, results showed that fine particle fractions (<5 μm) were 19, 29, 38 and 71% for solid lipid particles, micelles, nano-emulsion and liposomes, respectively. When the impaction method was applied, using a next generation pharmaceutical impactor operated at 30 l/min, results showed that fine particle fractions were 39, 78, 82 and 87% for solid lipid particles, micelles, nano-emulsion and liposomes, respectively. The differences observed between the results obtained from both methods confirm that the laser diffraction method is not always suitable for aerodynamic characterization of aerosols and should be validated against an impaction method. Nebulization of the drug-carrier systems led to an increase of their size most likely due to aggregation phenomena. The size was increased by a factor of 2-26 depending on the encapsulation system. The most important aggregation was obtained with nano-emulsion; the less one with solid lipid particles. The mass median aerodynamic diameter (MMAD) of the generated aerosols ranged from 1.76 to 6.10 μm. The application of a mathematical model, the Multiple-Path Particle Dosimetry (MPPD), for the prediction of the pulmonary deposit gave encouraging results. The rate of vitamin E able to reach the lung ranged from 37.6 (for the liposomes) to 51.6% (for the micelles). The obtained results showed that the different systems developed for vitamin E encapsulation were suitable to

  20. Cytoplasmic fungal lipases release fungicides from ultra-deformable vesicular drug carriers.

    Science.gov (United States)

    Steinberg, Gero

    2012-01-01

    The Transfersome® is a lipid vesicle that contains membrane softeners, such as Tween 80, to make it ultra-deformable. This feature makes the Transfersome® an efficient carrier for delivery of therapeutic drugs across the skin barrier. It was reported that TDT 067 (a topical formulation of 15 mg/ml terbinafine in Transfersome® vesicles) has a much more potent antifungal activity in vitro compared with conventional terbinafine, which is a water-insoluble fungicide. Here we use ultra-structural studies and live imaging in a model fungus to describe the underlying mode of action. We show that terbinafine causes local collapse of the fungal endoplasmic reticulum, which was more efficient when terbinafine was delivered in Transfersome® vesicles (TFVs). When applied in liquid culture, fluorescently labeled TFVs rapidly entered the fungal cells (T(1/2)~2 min). Entry was F-actin- and ATP-independent, indicating that it is a passive process. Ultra-structural studies showed that passage through the cell wall involves significant deformation of the vesicles, and depends on a high concentration of the surfactant Tween 80 in their membrane. Surprisingly, the TFVs collapsed into lipid droplets after entry into the cell and the terbinafine was released from their interior. With time, the lipid bodies were metabolized in an ATP-dependent fashion, suggesting that cytosolic lipases attack and degrade intruding TFVs. Indeed, the specific monoacylglycerol lipase inhibitor URB602 prevented Transfersome® degradation and neutralized the cytotoxic effect of Transfersome®-delivered terbinafine. These data suggest that (a) Transfersomes deliver the lipophilic fungicide Terbinafine to the fungal cell wall, (b) the membrane softener Tween 80 allows the passage of the Transfersomes into the fungal cell, and (c) fungal lipases digest the invading Transfersome® vesicles thereby releasing their cytotoxic content. As this mode of action of Transfersomes is independent of the drug cargo

  1. Cytoplasmic fungal lipases release fungicides from ultra-deformable vesicular drug carriers.

    Directory of Open Access Journals (Sweden)

    Gero Steinberg

    Full Text Available The Transfersome® is a lipid vesicle that contains membrane softeners, such as Tween 80, to make it ultra-deformable. This feature makes the Transfersome® an efficient carrier for delivery of therapeutic drugs across the skin barrier. It was reported that TDT 067 (a topical formulation of 15 mg/ml terbinafine in Transfersome® vesicles has a much more potent antifungal activity in vitro compared with conventional terbinafine, which is a water-insoluble fungicide. Here we use ultra-structural studies and live imaging in a model fungus to describe the underlying mode of action. We show that terbinafine causes local collapse of the fungal endoplasmic reticulum, which was more efficient when terbinafine was delivered in Transfersome® vesicles (TFVs. When applied in liquid culture, fluorescently labeled TFVs rapidly entered the fungal cells (T(1/2~2 min. Entry was F-actin- and ATP-independent, indicating that it is a passive process. Ultra-structural studies showed that passage through the cell wall involves significant deformation of the vesicles, and depends on a high concentration of the surfactant Tween 80 in their membrane. Surprisingly, the TFVs collapsed into lipid droplets after entry into the cell and the terbinafine was released from their interior. With time, the lipid bodies were metabolized in an ATP-dependent fashion, suggesting that cytosolic lipases attack and degrade intruding TFVs. Indeed, the specific monoacylglycerol lipase inhibitor URB602 prevented Transfersome® degradation and neutralized the cytotoxic effect of Transfersome®-delivered terbinafine. These data suggest that (a Transfersomes deliver the lipophilic fungicide Terbinafine to the fungal cell wall, (b the membrane softener Tween 80 allows the passage of the Transfersomes into the fungal cell, and (c fungal lipases digest the invading Transfersome® vesicles thereby releasing their cytotoxic content. As this mode of action of Transfersomes is independent of the

  2. 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.

  3. Facile fabrication of polyurethane microcapsules carriers for tracing cellular internalization and intracellular pH-triggered drug release.

    Science.gov (United States)

    Niu, Yuqing; Stadler, Florian J; Song, Jun; Chen, Siping; Chen, Shiguo

    2017-05-01

    A tailor-made traceable pH-sensitive drug delivery system based on polyurethane (PU) microcapsules was fabricated using a facile double-emulsion method containing 3,3'-dioctadecyloxacarbocyanine perchlorate, doxorubicin (DOX) and sodium bicarbonate (NaHCO 3 ). When PU microcapsules were immersed in acidic media, NaHCO 3 could react with the H + to quickly produce CO 2 bubbles to puncture the PU shell, resulting in rapid release of DOX to promptly reach the intracellular drug therapeutic threshold to kill cancer cells in a short period. Confocal laser scanning microscopic analysis showed that these traceable pH-sensitive drug carriers can be easily internalized by BGC 823 and Hela cells, and the loaded DOX can quickly release from PU microcapsules in the endo-/lysosomes to be mainly resided in cell nuclei. This traceable pH-sensitive drug carrier can achieve on-demand controlled release profiles for visualization of cancer therapy. Thus, it is a potential candidate for anticancer drug delivery system in advanced cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Dynamic mechanical behaviour of nanoparticle loaded biodegradable PVA films for vaginal drug delivery.

    Science.gov (United States)

    Traore, Yannick L; Fumakia, Miral; Gu, Jijin; Ho, Emmanuel A

    2018-03-01

    In this study, we investigated the viscoelastic and mechanical behaviour of polyvinyl alcohol films formulated along with carrageenan, plasticizing agents (polyethylene glycol and glycerol), and when loaded with nanoparticles as a model for potential applications as microbicides. The storage modulus, loss modulus and glass transition temperature were determined using a dynamic mechanical analyzer. Films fabricated from 2% to 5% polyvinyl alcohol containing 3 mg or 5 mg of fluorescently labeled nanoparticles were evaluated. The storage modulus and loss modulus values of blank films were shown to be higher than the nanoparticle-loaded films. Glass transition temperature determined using the storage modulus, and loss modulus was between 40-50℃ and 35-40℃, respectively. The tensile properties evaluated showed that 2% polyvinyl alcohol films were more elastic but less resistant to breaking compared to 5% polyvinyl alcohol films (2% films break around 1 N load and 5% films break around 7 N load). To our knowledge, this is the first study to evaluate the influence of nanoparticle and film composition on the physico-mechanical properties of polymeric films for vaginal drug delivery.

  5. The characters of self-assembly core/shell nanoparticles of amphiphilic hyperbranched polyethers as drug carriers

    International Nuclear Information System (INIS)

    Ajun Wan; Yuxia, Kou

    2008-01-01

    The characters of self-assembly core/shell nanoparticles of amphiphilic hyperbranched polyethers (HP-g-PEO) as drug carriers were investigated. The HP-g-PEO consisting of hydrophobic HP-g-PEO core and hydrophilic poly(ethylene glycol) arms was prepared by the cation ring-opening polymerization. A series of HP-g-PEO samples with different degree of branching (DB) were synthesized under various reaction temperatures. Nanoparticles (NP) were obtained by self-assembly of HP-g-PEO in aqueous media. The structure of resulting HP-g-PEO was characterized by IR, 13 CNMR and GPC. Dynamic light scattering and transmission electron microscopy were applied to characterize the sizes and size distributions of NP. The results demonstrated that the mean diameters of NP were less than 100 nm, which exhibited uniform spherical formations and narrow size distributions. Using hydrophobic drug Probucol (PRO) as model drug, the particle sizes of drug loaded NP were larger than relative blank NP. The drug loading efficiency (LE) and incorporation efficiency (IE) of these NP were achieved to 35 and 89%, respectively. The in vitro release of PRO from the NP exhibited a sustained release and the cumulative drugs released for more than 600 h. The most important factor to affect drug release was the value of DB of HP-g-PEO. With the DB of HP-g-PEO increasing, the size and size distribution of NP decreased as well as the release rate. However, the small DB was beneficial to the LE of NP. Nanoparticle size and size distribution, LE, IE, and drug release rate were slightly affected by the initial solution concentration of polyethers. The co-incorporated hydrophilic drug had influence slightly on the release of drug from drug loaded NP. The results of in vitro drug release suggested that the core/shell NP performed good controlled release behaviors with potential practice as novelty drug delivery vehicles

  6. The characters of self-assembly core/shell nanoparticles of amphiphilic hyperbranched polyethers as drug carriers

    Science.gov (United States)

    Ajun, Wan; Yuxia, Kou

    2008-03-01

    The characters of self-assembly core/shell nanoparticles of amphiphilic hyperbranched polyethers (HP-g-PEO) as drug carriers were investigated. The HP-g-PEO consisting of hydrophobic HP-g-PEO core and hydrophilic poly(ethylene glycol) arms was prepared by the cation ring-opening polymerization. A series of HP-g-PEO samples with different degree of branching (DB) were synthesized under various reaction temperatures. Nanoparticles (NP) were obtained by self-assembly of HP-g-PEO in aqueous media. The structure of resulting HP-g-PEO was characterized by IR, 13CNMR and GPC. Dynamic light scattering and transmission electron microscopy were applied to characterize the sizes and size distributions of NP. The results demonstrated that the mean diameters of NP were less than 100 nm, which exhibited uniform spherical formations and narrow size distributions. Using hydrophobic drug Probucol (PRO) as model drug, the particle sizes of drug loaded NP were larger than relative blank NP. The drug loading efficiency (LE) and incorporation efficiency (IE) of these NP were achieved to 35 and 89%, respectively. The in vitro release of PRO from the NP exhibited a sustained release and the cumulative drugs released for more than 600 h. The most important factor to affect drug release was the value of DB of HP-g-PEO. With the DB of HP-g-PEO increasing, the size and size distribution of NP decreased as well as the release rate. However, the small DB was beneficial to the LE of NP. Nanoparticle size and size distribution, LE, IE, and drug release rate were slightly affected by the initial solution concentration of polyethers. The co-incorporated hydrophilic drug had influence slightly on the release of drug from drug loaded NP. The results of in vitro drug release suggested that the core/shell NP performed good controlled release behaviors with potential practice as novelty drug delivery vehicles.

  7. Meta-Analysis of Randomized Clinical Trials Comparing Biodegradable Polymer Drug-Eluting Stent to Second-Generation Durable Polymer Drug-Eluting Stents.

    Science.gov (United States)

    El-Hayek, Georges; Bangalore, Sripal; Casso Dominguez, Abel; Devireddy, Chandan; Jaber, Wissam; Kumar, Gautam; Mavromatis, Kreton; Tamis-Holland, Jacqueline; Samady, Habib

    2017-03-13

    The authors sought to perform a meta-analysis of randomized clinical trials (RCTs) comparing the safety and efficacy of biodegradable polymer drug-eluting stents (BP-DES) to second-generation durable polymer drug-eluting stents (DP-DES). Prior meta-analyses have established the superiority of BP-DES over bare-metal stents and first-generation DP-DES; however, their advantage compared with second-generation DP-DES remains controversial. The authors searched PubMed and Scopus databases for RCTs comparing BP-DES to the second-generation DP-DES. Outcomes included target vessel revascularization (TVR) as efficacy outcome and cardiac death, myocardial infarction (MI), and definite or probable stent thrombosis (ST) as safety outcomes. In addition, we performed landmark analysis for endpoints beyond 1 year of follow-up and a subgroup analysis based on the stent characteristics. The authors included 16 RCTs comprising 19,886 patients in the meta-analysis. At the longest available follow-up (mean duration 26 months), we observed no significant differences in TVR (p = 0.62), cardiac death (p = 0.46), MI (p = 0.98), or ST (risk ratio: 0.83, 95% confidence interval: 0.64 to 1.09; p = 0.19). Our landmark analysis showed that BP-DES were not associated with a reduction in the risk of very late ST (risk ratio: 0.87, 95% confidence interval: 0.49 to 1.53; p = 0.62). Similar outcomes were seen regardless of the eluting drug (biolimus vs. sirolimus), the stent platform (stainless steel vs. alloy), the kinetics of polymer degradation or drug release (6 months), the strut thickness of the BP-DES (thin 100 μm), or the DAPT duration (≥6 months vs. ≥12 months). BP-DES have similar safety and efficacy profiles to second-generation DP-DES. Published by Elsevier Inc.

  8. DNA-interactive properties of crotamine, a cell-penetrating polypeptide and a potential drug carrier.

    Directory of Open Access Journals (Sweden)

    Pei-Chun Chen

    effective nucleic acid drug delivery vehicles which take advantage of crotamine as a carrier with specificity for actively proliferating cells.

  9. Impulsion of nanoparticles as a drug carrier for the theoretical investigation of stenosed arteries with induced magnetic effects

    Energy Technology Data Exchange (ETDEWEB)

    Nadeem, S.; Ijaz, S., E-mail: shagufta.me2011@yahoo.com

    2016-07-15

    In this paper hemodynamics of stenosis are discussed to predict effect of atherosclerosis by means of mathematical models in the presence of uniform transverse magnetic field. The analysis is carried out using silver and copper nanoparticles as a drug carrier. Exact solution for the fluid temperature, velocity, axial induced magnetic field and current density distribution are obtained under mild stenosis approximation. The results indicate that with an increase in the concentration of nanoparticle hemodynamics effects of stenosis reduces throughout the inclined composite stenosed arteries. The considered analysis also summarizes that the drug silver nanoparticles is more efficient to reduce hemodynamics of stenosis when compare to the drug copper nanoparticle. In future this model could be helpful to predict important properties in some biomedical applications. - Highlights: • The contribution of copper and silver nanoparticles as drug carrier reveals that they are important to reduce hemodynamic of stenosis. • The heat is dissipated throughout the considered inclined artery with an increase in the nanoparticle volume fraction. • The stress on the wall of inclined arteries decreases with an increase in the magnetic Reynolds number and Strommers number.

  10. Towards improved solubility of poorly water-soluble drugs: cryogenic co-grinding of piroxicam with carrier polymers.

    Science.gov (United States)

    Penkina, Anna; Semjonov, Kristian; Hakola, Maija; Vuorinen, Sirpa; Repo, Timo; Yliruusi, Jouko; Aruväli, Jaan; Kogermann, Karin; Veski, Peep; Heinämäki, Jyrki

    2016-01-01

    Amorphous solid dispersions (SDs) open up exciting opportunities in formulating poorly water-soluble active pharmaceutical ingredients (APIs). In the present study, novel catalytic pretreated softwood cellulose (CPSC) and polyvinylpyrrolidone (PVP) were investigated as carrier polymers for preparing and stabilizing cryogenic co-ground SDs of poorly water-soluble piroxicam (PRX). CPSC was isolated from pine wood (Pinus sylvestris). Raman and Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used for characterizing the solid-state changes and drug-polymer interactions. High-resolution scanning electron microscope (SEM) was used to analyze the particle size and surface morphology of starting materials and final cryogenic co-ground SDs. In addition, the molecular aspects of drug-polymer interactions and stabilization mechanisms are presented. The results showed that the carrier polymer influenced both the degree of amorphization of PRX and stabilization against crystallization. The cryogenic co-ground SDs prepared from PVP showed an enhanced dissolution rate of PRX, while the corresponding SDs prepared from CPSC exhibited a clear sustained release behavior. In conclusion, cryogenic co-grinding provides a versatile method for preparing amorphous SDs of poorly water-soluble APIs. The solid-state stability and dissolution behavior of such co-ground SDs are to a great extent dependent on the carrier polymer used.

  11. Natural gums and modified natural gums as sustained-release carriers.

    Science.gov (United States)

    Bhardwaj, T R; Kanwar, M; Lal, R; Gupta, A

    2000-10-01

    Although natural gums and their derivatives are used widely in pharmaceutical dosage forms, their use as biodegradable polymeric materials to deliver bioactive agents has been hampered by the synthetic materials. These natural polysaccharides do hold advantages over the synthetic polymers, generally because they are nontoxic, less expensive, and freely available. Natural gums can also be modified to have tailor-made materials for drug delivery systems and thus can compete with the synthetic biodegradable excipients available in the market. In this review, recent developments in the area of natural gums and their derivatives as carriers in the sustained release of drugs are explored.

  12. Preparation and characterization of PEGylated multiwall carbon nanotubes as covalently conjugated and non-covalent drug carrier: A comparative study.

    Science.gov (United States)

    Habibizadeh, Mina; Rostamizadeh, Kobra; Dalali, Naser; Ramazani, Ali

    2017-05-01

    In this study, PEGylated multiwall carbon nanotubes (MWNTs)-based drug delivery system was developed. Ibuprofen as a model drug was loaded by physical and chemical method. The surface functionalization of nanotubes was carried out by enrichment of acylated groups. In order to synthesis PEGylated MWNTs, hydrophilic diamino-polyethylene glycol was covalently linked to the MWNTs surface via amidation reaction. Finally, ibuprofen was chemically and physically loaded on the PEGylated MWNTs. The resultants were characterized by FTIR, AFM, and DLS techniques. Cytotoxicity of PEGylated MWNTs were examined by MTT assay and the results revealed that PEG functionalized nanotubes did not show significant detrimental effects on the viability of L929 Cells. The percent of drug loading for chemically and physically drug payload carrier were determined to be 52.5% and 38%, respectively. The release of ibuprofen from covalently conjugated and non-covalent drug loaded PEGylated MWNTs at pH=7.4, and 5.3 were investigated, as well. From the results, it was found that chemically loaded MWNTs showed much sustained release behavior compared to the physically loaded one, especially at pH=5.3. The kinetic of drug release was also investigated. The results strongly suggest that the chemically conjugated PEGylated MWNTs could be used as controlled release system for various drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Radiation preparation of drug carriers based polyacrylic acid (PAAc) using poly(vinyl pyrrolidone) (PVP) as a template polymer

    Energy Technology Data Exchange (ETDEWEB)

    Abd El-Rehim, H.A. [National Center for Radiation Research and Technology, Poymer, 3-Ahmed El-Zomor, P.O. Box 29, Cairo, Naser City (Egypt)]. E-mail: ha_rehim@hotmail.com; Hegazy, E.A. [National Center for Radiation Research and Technology, Poymer, 3-Ahmed El-Zomor, P.O. Box 29, Cairo, Naser City (Egypt); Khalil, F.H. [National Center for Radiation Research and Technology, Poymer, 3-Ahmed El-Zomor, P.O. Box 29, Cairo, Naser City (Egypt); Hamed, N.A. [National Center for Radiation Research and Technology, Poymer, 3-Ahmed El-Zomor, P.O. Box 29, Cairo, Naser City (Egypt)

    2007-01-15

    The present study deals with the radiation synthesis of stimuli response hydrophilic polymers from polyacrylic acid (PAAc). To maintain the property of PAAc and control the water swellibility for its application as a drug delivery system, radiation polymerization of AAc in the presence of poly(vinyl pyrrolidone) (PVP) as a template polymer was carried out. Characterization of the prepared PAA/PVP inter-polymer complex was investigated by determining gel content, swelling property, hydrogel microstructure and the release rate of caffeine as a model drug. The release rate of caffeine from the PAA/PVP inter-polymer complexes showed pH-dependency, and seemed to be mainly controlled by the dissolution rate of the complex above a pK {sub a} of PAAc. The prepared inter-polymer complex could be used for application as drug carriers.

  14. Biodegradable Polymers

    OpenAIRE

    Vroman, Isabelle; Tighzert, Lan

    2009-01-01

    Biodegradable materials are used in packaging, agriculture, medicine and other areas. In recent years there has been an increase in interest in biodegradable polymers. Two classes of biodegradable polymers can be distinguished: synthetic or natural polymers. There are polymers produced from feedstocks derived either from petroleum resources (non renewable resources) or from biological resources (renewable resources). In general natural polymers offer fewer advantages than synthetic polymers. ...

  15. Doxorubicin-conjugated core-shell magnetite nanoparticles as dual-targeting carriers for anticancer drug delivery.

    Science.gov (United States)

    Sadighian, Somayeh; Rostamizadeh, Kobra; Hosseini-Monfared, Hassan; Hamidi, Mehrdad

    2014-05-01

    The present study reports the successful synthesis of core-shell nanostructures composed of magnetite nanoparticles (Fe3O4-NPs) conjugated to the anticancer drug doxorubicin, intended for dual targeting of the drug to the tumor sites via a combination of the magnetic attraction and the pH-sensitive cleavage of the drug-particle linkages along with a longer circulation time and reduced side effects. To improve the carrier biocompatibility, the prepared nanocarrier was, finally coated by chitosan. FT-IR analysis confirmed the synthesis of functionalized Fe3O4-NPs, doxorubicin-conjugated Fe3O4-NPs, and chitosan-coated nanocarriers. Scanning electron microscopy (SEM) indicated the formation of spherical nanostructures with the final average particle size of around 50 nm. The vibrating sample magnetometer (VSM) analysis showed that the saturation magnetization value (Ms) of carrier was 6 emu/g. The drug release behavior from the nanocarriers was investigated both in acidic and neutral buffered solutions (pH values of 5.3 and 7.4, respectively) and showed two-fold increase in the extent of drug release at pH 5.3 compared to pH 7.4 during 7 days. The results showed that the dual-targeting nanocarriers responded successfully to the external magnetic field and pH. From the results obtained, it can be concluded that this methodology can be used to target and improve therapeutic efficacy of the anticancer drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Chemical template-assisted synthesis of monodisperse rattle-type Fe3O4@C hollow microspheres as drug carrier.

    Science.gov (United States)

    Cheng, Lin; Ruan, Weimin; Zou, Bingfang; Liu, Yuanyuan; Wang, Yongqiang

    2017-08-01

    A chemical template strategy was put forward to synthesize monodisperse rattle-type magnetic carbon (Fe 3 O 4 @C) hollow microspheres. During the synthesis procedure, monodisperse Fe 2 O 3 microspheres were used as chemical template, which released Fe 3+ ions in acidic solution and initiated the in-situ polymerization of pyrrole into polypyrrole (PPy) shell. With the continual acidic etching of Fe 2 O 3 microspheres, rattle-type Fe 2 O 3 @PPy microspheres were generated with the cavity appearing between the PPy shell and left Fe 2 O 3 core, which were then transformed into Fe 3 O 4 @C hollow microspheres through calcination in nitrogen atmosphere. Compared with traditional physical template, the shell and cavity of rattle-type hollow microspheres were generated in one step using the chemical template method, which obviously saved the complex procedures including the coating and removal of middle shells. The experimental results exhibited that the rattle-type Fe 3 O 4 @C hollow microspheres with different parameters could be regulated through controlled synthesis of the intermediate Fe 2 O 3 @PPy product. Moreover, when the rattle-type Fe 3 O 4 @C hollow microspheres were investigated as drug carrier, they manifested sustained-release behaviour of doxorubicin, justifying their promising applications as carriers in drug delivery. The aim of the present study was first to synthesize rattle-type Fe 3 O 4 @C hollow microspheres through a simple synthesis method as a drug carrier. Here a chemical template synthesis of rattle-type hollow microspheres was developed, which saved the complex procedures including the coating and removal of middle shells in traditional physical template. Second, all the influence factors in the reaction processes were systematically investigated to obtain rattle-type Fe 3 O 4 @C hollow microspheres with controlled parameters. Third, the rattle-type Fe 3 O 4 @C hollow microspheres were studied as drug carriers and the influences of their

  17. Self-assembly of biodegradable copolyester and reactive HPMA-based polymers into nanoparticles as an alternative stealth drug delivery system

    Czech Academy of Sciences Publication Activity Database

    Jäger, Eliezer; Jäger, Alessandro; Etrych, Tomáš; Giacomelli, F. C.; Chytil, Petr; Jigounov, Alexander; Putaux, J.-L.; Říhová, Blanka; Ulbrich, Karel; Štěpánek, Petr

    2012-01-01

    Roč. 8, č. 37 (2012), s. 9563-9575 ISSN 1744-683X R&D Projects: GA AV ČR IAAX00500803; GA ČR GAP208/10/1600 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510 Institutional support: RVO:61389013 ; RVO:61388971 Keywords : biodegradable nanoparticles * light scattering from polymer nanoparticles * doxorubicin drug release Subject RIV: CF - Physical ; Theoretical Chemistry; EC - Immunology (MBU-M) Impact factor: 3.909, year: 2012

  18. Novel Amphiphilic, Biodegradable, Biocompatible, Thermo-Responsive ABA Triblock Copolymers Based on PCL and PEG Analogues via a Combination of ROP and RAFT: Synthesis, Characterization, and Sustained Drug Release from Self-Assembled Micelles

    Directory of Open Access Journals (Sweden)

    Wenyan Ning

    2018-02-01

    Full Text Available Well-defined novel, linear, biodegradable, amphiphilic thermo-responsive ABA-type triblock copolymers, poly[2-(2-methoxyethoxy ethyl methacrylate-co-oligo(ethylene glycol methacrylate]-b-poly(ε-caprolactone-b-poly[2-(2-methoxyethoxy ethyl methacrylate-co-oligo(ethylene glycol methacrylate] [P(MEO2MA-co-OEGMA-b-PCL-b-P(MEO2MA-co-OEGMA] (tBPs, were synthesized via a combination of ring-opening polymerization (ROP of ε-caprolactone (εCL and reversible addition-fragmentation chain transfer polymerization (RAFT of MEO2MA and OEGMA comonomers. The chemical structures and compositions of these copolymers were characterized using Fourier transform infrared spectroscopy (FT-IR and proton nuclear magnetic resonance (1H NMR. The molecular weights of the copolymers were obtained using gel permeation chromatography (GPC measurements. Thermo-responsive micelles were obtained by self-assembly of copolymers in aqueous medium. The temperature sensitivity and micelllization behavior of amphiphilic triblock copolymers solutions were studied by transmittance, fluorescence probe, surface tension, dynamic light scattering (DLS and transmission electron microscopy (TEM. A hydrophobic drug, anethole, was encapsulated in micelles by using the dialysis method. The average particle sizes of drug-loaded micelles were determined by dynamic light scattering measurement. In vitro, the sustained release of the anethole was performed in pH 7.4 phosphate-buffered saline (PBS at different temperatures. Results showed that the triblock copolymer’s micelles were quite effective in the encapsulation and controlled release of anethole. The vial inversion test demonstrated that the triblock copolymers could trigger the sol-gel transition which also depended on the temperature, and its sol-gel transition temperature gradually decreased with increasing concentration. The hydrogel system could also be used as a carrier of hydrophobic drugs in medicine.

  19. Formulation of Biologically-Inspired Silk-Based Drug Carriers for Pulmonary Delivery Targeted for Lung Cancer.

    Science.gov (United States)

    Kim, Sally Yunsun; Naskar, Deboki; Kundu, Subhas C; Bishop, David P; Doble, Philip A; Boddy, Alan V; Chan, Hak-Kim; Wall, Ivan B; Chrzanowski, Wojciech

    2015-08-03

    The benefits of using silk fibroin, a major protein in silk, are widely established in many biomedical applications including tissue regeneration, bioactive coating and in vitro tissue models. The properties of silk such as biocompatibility and controlled degradation are utilized in this study to formulate for the first time as carriers for pulmonary drug delivery. Silk fibroin particles are spray dried or spray-freeze-dried to enable the delivery to the airways via dry powder inhalers. The addition of excipients such as mannitol is optimized for both the stabilization of protein during the spray-freezing process as well as for efficient dispersion using an in vitro aerosolisation impactor. Cisplatin is incorporated into the silk-based formulations with or without cross-linking, which show different release profiles. The particles show high aerosolisation performance through the measurement of in vitro lung deposition, which is at the level of commercially available dry powder inhalers. The silk-based particles are shown to be cytocompatible with A549 human lung epithelial cell line. The cytotoxicity of cisplatin is demonstrated to be enhanced when delivered using the cross-linked silk-based particles. These novel inhalable silk-based drug carriers have the potential to be used as anti-cancer drug delivery systems targeted for the lungs.

  20. Development of Triamcinolone Acetonide-Loaded Nanostructured Lipid Carriers (NLCs) for Buccal Drug Delivery Using the Box-Behnken Design.

    Science.gov (United States)

    Kraisit, Pakorn; Sarisuta, Narong

    2018-04-23

    The aim of this present work was to prepare triamcinolone acetonide (TA)-loaded nanostructured lipid carriers (TA-loaded NLCs) for buccal drug delivery systems using the Box-Behnken design. A hot homogenization method was used to prepare the TA-loaded NLCs. Spermaceti (X₁), soybean oil (X₂), and Tween 80 (X₃) were used as solid lipid, liquid lipid, and stabilizer, respectively. The particle size of TA-loaded NLCs was lower than 200 nm and the zeta potential displayed the negative charge in all formulations. The percentage encapsulation efficiency (%EE) of the TA-loaded NLCs showed that it was higher than 80% for all formulations. Field emission scanning electron microscope (FESEM) confirmed that the size of TA-loaded NLCs was approximately 100 nm and energy-dispersive X-ray spectroscopy (EDS) confirmed that the TA could be incorporated in the NLC system. The Higuchi model gave the highest value of the R², indicating that this model was a fit for the TA release profiles of TA-loaded NLCs. Confocal laser scanning microscopy (CLSM) was used to observe the drug penetration within the porcine buccal mucosa and Nile red-loaded NLCs showed significantly higher penetration depth at 8 h than at 2 h. Therefore, TA-loaded NLCs could be an efficient carrier for drug delivery through the buccal mucosa.

  1. Improving the dissolution rate of hydrophobic drugs through encapsulation in porous lactose as a new biocompatible porous carrier.

    Science.gov (United States)

    Ebrahimi, Amirali; Saffari, Morteza; Langrish, Timothy

    2017-04-15

    T he dissolution rates of indomethacin (IMC) and nifedipine (NIF) as poorly water-soluble model drugs have been significantly improved by encapsulating their molecules in the porous structure of engineered-particles of lactose as a new biocompatible porous carrier. The formulation method used in this study utilized a template-based spray-drying technique for in-situ production of porous lactose followed by two solvent-based drug-loading methods: (i) adsorption from organic solution, and (ii) incipient wetness impregnation to incorporate the drugs inside the porous lactose. In both cases, the results of DSC and XRD have revealed the deposition of nano-sized crystals of drugs inside the nanopores due to the nanoconfinement phenomenon. Greater extents of drug loadings have been achieved during the indomethacin adsorption due to the hydrogen-bonding interaction with the surface of lactose, as determined by FTIR spectroscopy. The in vitro release studies in simulated gastric fluid (SGF) have shown faster release rates for the impregnated particles compared with drug-loaded particles via the adsorption method. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Recent advances in compartmentalized synthetic architectures as drug carriers, cell mimics and artificial organelles

    DEFF Research Database (Denmark)

    York-Durán, María José; Gallardo, Maria Godoy; Labay, Cédric Pierre

    2017-01-01

    significant research attention and these assemblies are proposed as candidate materials for a range of biomedical applications. In this Review article, the recent successes of multicompartment architectures as carriers for the delivery of therapeutic cargo or the creation of micro- and nanoreactors that mimic...

  3. Bioactive albumin-based carriers for tumour chemotherapy.

    Science.gov (United States)

    Shahzad, Yasser; Khan, Ikram Ullah; Hussain, Talib; Alamgeer; Serra, Christophe A; Rizvi, Syed A A; Gerber, Minja; du Plessis, Jeanetta

    2014-01-01

    Proteins are posed as the natural counterpart of the synthetic polymers for the development of drug delivery systems and few of them, have been regarded safe for drug delivery purposes by the United States Food and Drug Administration (FDA). Serum albumin is the most abundant protein in human blood. Interest in the exploration of pharmaceutical applications of albumin-based drug delivery carriers, especially for the delivery of chemotherapeutic agents, has increased in recent years. Albumin has several advantages over synthetic polymers, as it is biocompatible, biodegradable, has low cytotoxicity and has an excellent binding capacity with various drugs. Micro- and nano-carriers not only protect active pharmaceutical ingredients against degradation, but also offer a prolonged release of drugs in a controlled fashion. Since existing tumour chemotherapeutic agents neither target tumour cells, nor are they specific to tumour cells, a slow release of drugs from carriers would be beneficial in targeting carcinogenic cells intracellularly. This article aims at providing an overview of pharmaceutical applications of albumin as a drug delivery carrier in tumour chemotherapy.

  4. Simple and cost-effective fabrication of solid biodegradable polymer microneedle arrays with adjustable aspect ratio for transdermal drug delivery using acupuncture microneedles

    International Nuclear Information System (INIS)

    Cha, Kyoung Je; Kim, Taewan; Park, Sung Jea; Kim, Dong Sung

    2014-01-01

    Polymer microneedle arrays (MNAs) have received much attention for their use in transdermal drug delivery and microneedle therapy systems due to the advantages they offer, such as low cost, good mechanical properties, and a versatile choice of materials. Here, we present a simple and cost-effective method for the fabrication of a biodegradable polymer MNA in which the aspect ratio of each microneedle is adjustable using commercially available acupuncture microneedles. In our process, a master template with acupuncture microneedles, whose shape will be the final MNA, was carefully prepared by fixing them onto a plastic substrate with selectively drilled holes which, in turn, determine the aspect ratios of the microneedles. A polylactic acid (PLA; a biodegradable polymer) MNA was fabricated by a micromolding process with a polydimethylsiloxane (PDMS) mold containing the cavity of the microneedles, which was obtained by the PDMS replica molding against the master template. The mechanical force and degradation behavior of the replicated PLA MNA were characterized with the help of a compression test and an accelerated degradation test, respectively. Finally, the transdermal drug delivery performance of the PLA MNA was successfully simulated by two different methods of penetration and staining, using the skin of a pig cadaver. These results indicated that the proposed method can be effectively used for the fabrication of polymer MNAs which can be used in various microneedle applications. (paper)

  5. Simple and cost-effective fabrication of solid biodegradable polymer microneedle arrays with adjustable aspect ratio for transdermal drug delivery using acupuncture microneedles

    Science.gov (United States)

    Cha, Kyoung Je; Kim, Taewan; Jea Park, Sung; Kim, Dong Sung

    2014-11-01

    Polymer microneedle arrays (MNAs) have received much attention for their use in transdermal drug delivery and microneedle therapy systems due to the advantages they offer, such as low cost, good mechanical properties, and a versatile choice of materials. Here, we present a simple and cost-effective method for the fabrication of a biodegradable polymer MNA in which the aspect ratio of each microneedle is adjustable using commercially available acupuncture microneedles. In our process, a master template with acupuncture microneedles, whose shape will be the final MNA, was carefully prepared by fixing them onto a plastic substrate with selectively drilled holes which, in turn, determine the aspect ratios of the microneedles. A polylactic acid (PLA; a biodegradable polymer) MNA was fabricated by a micromolding process with a polydimethylsiloxane (PDMS) mold containing the cavity of the microneedles, which was obtained by the PDMS replica molding against the master template. The mechanical force and degradation behavior of the replicated PLA MNA were characterized with the help of a compression test and an accelerated degradation test, respectively. Finally, the transdermal drug delivery performance of the PLA MNA was successfully simulated by two different methods of penetration and staining, using the skin of a pig cadaver. These results indicated that the proposed method can be effectively used for the fabrication of polymer MNAs which can be used in various microneedle applications.

  6. A 3D polyhedral metal–organic framework as drug carrier for ...

    African Journals Online (AJOL)

    A new fabrication of {[H3O][Cu6(tpta)3(DMA)4(COO)]∙12H2O∙7DMA} (1) was used as a drug vehicle of 5-fluorouracil (5-FU) for drug delivery. The incorporation of the drug 5-FU into the 1 was around 47.3 wt% per gram of dehydrated 1. Cargo release behavior and material degradation profile were also investigated under ...

  7. Characterization of the interaction forces in a drug carrier complex of doxorubicin with a drug-binding peptide.

    Science.gov (United States)

    Gocheva, Gergana; Ilieva, Nina; Peneva, Kalina; Ivanova, Anela

    2018-04-01

    Polypeptide-based materials are used as building blocks for drug delivery systems aimed at toxicity decrease in chemotherapeutics. A molecular-level approach is adopted for investigating the non-covalent interactions between doxorubicin and a recently synthesized drug-binging peptide as a key part of a system for delivery to neoplastic cells. Molecular dynamics simulations in aqueous solution at room and body temperature are applied to investigate the structure and the binding modes within the drug-peptide complex. The tryptophans are outlined as the main chemotherapeutic adsorption sites, and the importance of their placement in the peptide sequence is highlighted. The drug-peptide binging energy is evaluated by density functional theory calculations. Principal component analysis reveals comparable importance of several types of interaction for the binding strength. π-Stacking is dominant, but other factors are also significant: intercalation, peptide backbone stacking, electrostatics, dispersion, and solvation. Intra- and intermolecular H-bonding also stabilizes the complexes. The influence of solvent molecules on the binding energy is mild. The obtained data characterize the drug-to-peptide attachment as a mainly attractive collective process with interactions spanning a broad range of values. These results explain with atomistic detail the experimentally registered doxorubicin-binging ability of the peptide and outline the complex as a prospective carrying unit that can be employed in design of drug delivery systems. © 2017 John Wiley & Sons A/S.

  8. Biodegradable polymer drug-eluting stents versus first-generation durable polymer drug-eluting stents: A systematic review and meta-analysis of 12 randomized controlled trials.

    Science.gov (United States)

    Bundhun, Pravesh Kumar; Pursun, Manish; Huang, Feng

    2017-11-01

    Even if drug-eluting stents (DES) showed beneficial effects in patients with coronary artery diseases (CADs), limitations have been observed with the first-generation durable polymer DES (DP-DES). Recently, biodegradable polymer DES (BP-DES) have been approved to be used as an alternative to DP-DES, with potential benefits. We aimed to systematically compare BP-DES with the first-generation DP-DES using a large number of randomized patients. Electronic databases were searched for randomized controlled trials (RCTs) comparing BP-DES with first-generation DP-DES. The main endpoints were the long-term (≥2 years) adverse clinical outcomes that were reported with these 2 types of DES. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) and the analysis was carried out by RevMan 5.3 software. Twelve trials with a total number of 13,480 patients (7730 and 5750 patients were treated by BP-DES and first-generation DP-DES, respectively) were included. During a long-term follow-up period of ≥2 years, mortality, myocardial infarction (MI), target lesion revascularization (TLR), and major adverse cardiac events (MACEs) were not significantly different between these 2 groups with OR: 0.84, 95% CI: 0.66-1.07; P = .16, I = 0%, OR: 1.01, 95% CI: 0.45-2.27; P = .98, I = 0%, OR: 0.91, 95% CI: 0.75-1.11; P = .37, I = 0% and OR: 0.86, 95% CI: 0.44-1.67; P = .65, I = 0%, respectively. Long-term total stent thrombosis (ST), definite ST, and probable ST were also not significantly different between BP-DES and the first-generation DP-DES with OR: 0.77, 95% CI: 0.50-1.18; P = .22, I = 0%, OR: 0.71, 95% CI: 0.43-1.18; P = .19, I = 0% and OR: 1.31, 95% CI: 0.56-3.08; P = .53, I = 6%, respectively. Long-term mortality, MI, TLR, MACEs, and ST were not significantly different between BP-DES and the first-generation DP-DES. However, the follow-up period was restricted to only 3 years in this analysis. Copyright © 2017

  9. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges.

    Science.gov (United States)

    Ha, Dinh; Yang, Ningning; Nadithe, Venkatareddy

    2016-07-01

    Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body׳s own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed.

  10. Renal targeting potential of a polymeric drug carrier, poly-l-glutamic acid, in normal and diabetic rats.

    Science.gov (United States)

    Chai, Hann-Juang; Kiew, Lik-Voon; Chin, Yunni; Norazit, Anwar; Mohd Noor, Suzita; Lo, Yoke-Lin; Looi, Chung-Yeng; Lau, Yeh-Siang; Lim, Tuck-Meng; Wong, Won-Fen; Abdullah, Nor Azizan; Abdul Sattar, Munavvar Zubaid; Johns, Edward J; Chik, Zamri; Chung, Lip-Yong

    2017-01-01

    Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier. 3 H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3 H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF). In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state. The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal targeting drug carrier.

  11. Nanodrug-enhanced radiofrequency tumor ablation: effect of micellar or liposomal carrier on drug delivery and treatment efficacy.

    Directory of Open Access Journals (Sweden)

    Marwan Moussa

    Full Text Available To determine the effect of different drug-loaded nanocarriers (micelles and liposomes on delivery and treatment efficacy for radiofrequency ablation (RFA combined with nanodrugs.Fischer 344 rats were used (n = 196. First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of i.v. fluorescent beads (20, 100, and 500 nm, with fluorescent intensity measured at 4-24 hr. Next, to study carrier type on drug efficiency, RFA was combined with micellar (20 nm or liposomal (100 nm preparations of doxorubicin (Dox; targeting HIF-1α or quercetin (Qu; targeting HSP70. Animals received RFA alone, RFA with Lipo-Dox or Mic-Dox (1 mg i.v., 15 min post-RFA, and RFA with Lipo-Qu or Mic-Qu given 24 hr pre- or 15 min post-RFA (0.3 mg i.v.. Tumor coagulation and HIF-1α or HSP70 expression were assessed 24 hr post-RFA. Third, the effect of RFA combined with i.v. Lipo-Dox, Mic-Dox, Lipo-Qu, or Mic-Qu (15 min post-RFA compared to RFA alone on tumor growth and animal endpoint survival was evaluated. Finally, drug uptake was compared between RFA/Lipo-Dox and RFA/Mic-Dox at 4-72 hr.Smaller 20 nm beads had greater deposition and deeper tissue penetration in both tumor (100 nm/500 nm and liver (100 nm (p<0.05. Mic-Dox and Mic-Qu suppressed periablational HIF-1α or HSP70 rim thickness more than liposomal preparations (p<0.05. RFA/Mic-Dox had greater early (4 hr intratumoral doxorubicin, but RFA/Lipo-Dox had progressively higher intratumoral doxorubicin at 24-72 hr post-RFA (p<0.04. No difference in tumor growth and survival was seen between RFA/Lipo-Qu and RFA/Mic-Qu. Yet, RFA/Lipo-Dox led to greater animal endpoint survival compared to RFA/Mic-Dox (p<0.03.With RF ablation, smaller particle micelles have superior penetration and more effective local molecular modulation. However, larger long-circulating liposomal carriers can result in greater intratumoral drug accumulation over time and reduced tumor growth. Accordingly

  12. 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

  13. Liquid crystalline phase as a probe for crystal engineering of lactose: carrier for pulmonary drug delivery.

    Science.gov (United States)

    Patil, Sharvil S; Mahadik, Kakasaheb R; Paradkar, Anant R

    2015-02-20

    The current work was undertaken to assess suitability of liquid crystalline phase for engineering of lactose crystals and their utility as a carrier in dry powder inhalation formulations. Saturated lactose solution was poured in molten glyceryl monooleate which subsequently transformed into gel. The gel microstructure was analyzed by PPL microscopy and SAXS. Lactose particles recovered from gels after 48 h were analyzed for polymorphism using techniques such as FTIR, XRD, DSC and TGA. Particle size, morphology and aerosolisation properties of prepared lactose were analyzed using Anderson cascade impactor. In situ seeding followed by growth of lactose crystals took place in gels with cubic microstructure as revealed by PPL microscopy and SAXS. Elongated (size ∼ 71 μm) lactose particles with smooth surface containing mixture of α and β-lactose was recovered from gel, however percentage of α-lactose was more as compared to β-lactose. The aerosolisation parameters such as RD, ED, %FPF and % recovery of lactose recovered from gel (LPL) were found to be comparable to Respitose® ML001. Thus LC phase (cubic) can be used for engineering of lactose crystals so as to obtain particles with smooth surface, high elongation ratio and further they can be used as carrier in DPI formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Polyelectrolyte Multilayer Film Coated Silver Nanorods: An Effective Carrier System for Externally Activated Drug Delivery

    Science.gov (United States)

    Paramasivam, Gokul; Sharma, Varsha; Sundaramurthy, Anandhakumar

    2017-08-01

    Nanoparticle anisotropy offers unique functions and features in comparison with spherical nanoparticles (NPs) and makes anisotropic nanoparticles (ANPs) promising candidates in applications like drug delivery, imaging, biosensing and theranostics. Presence of surface active groups (e.g. amine, and carboxylate groups) on their surface provides binding sites for ligands or other biomolecules, and hence, this could be targeted for specific part or cells in our body. In the quest of such surface modification, functionalization of ANPs along Layer-by-Layer (LbL) coating of oppositely charged polyelectrolytes (PE) reduces cellular toxicity and promotes easy encapsulation of drugs. In this work, we report the silver nanorods (AgNRs) synthesis by adsorbate directed synthetic approach using cetyltrimethyl ammonium bromide (CTAB). The formed ANPs is investigated by scanning electron microscopy (SEM) and UV-Visible (UV-Vis) spectroscopy revealing the shaping of AgNRs of 3-16 nm aspect ratio with some presence of triangles. These NRs were further coated with bio polymers of chitosan (CH) and dextran sulphate (DS) through LbL approach and used for encapsulation of water soluble anti-bacterial drugs like ciprofloxacin hydrochloride (CFH). The encapsulation of drugs and profiles of drug release were investigated and compared to that of spherical silver nanoparticles (AgNPs). The added advantages of the proposed drug delivery system (DDS) can be externally activated to release the loaded drug and used as contrast agents for biological imaging under exposure to NIR light. Such system shows unique and attractive characteristics required for drug delivery and bioimaging thus offering the scope for further development as theranostic material.

  15. Hollow microspheres as a drug carrier: An overview of fabrication and in vivo characterization techniques

    Directory of Open Access Journals (Sweden)

    Avinash Kurrey

    2014-01-01

    Full Text Available Oral controlled release dosage forms encounter several physiological constraints like inability to retain and locate the controlled drug delivery system within the desired region of the gastrointestinal tract (GIT due to variation in gastric emptying. This leads to non - uniform absorption profile, insufficient drug release and shorter residence time of the dosage form in the stomach. As the fallout of this event, there is incomplete absorption of the drug having absorption window especially, in the upper part of GIT. These considerations have led to the development of oral controlled release dosage forms with gastroretentive properties. Hollow microspheres hold promise as one of the potential approaches for gastric retention. Hollow microspheres are spherical empty particles without core and can remain in the gastric region for prolonged periods. They significantly extend the gastric residence time of drugs, thereby improving bioavailability, reduced the drug waste and improved solubility for drugs that are less soluble at a higher pH environment. This review attempts to bring more insight into recent advances in methods of fabrication techniques and applications of hollow microspheres.

  16. Europium-doped amorphous calcium phosphate porous nanospheres: preparation and application as luminescent drug carriers

    Directory of Open Access Journals (Sweden)

    Zhang Kui-Hua

    2011-01-01

    Full Text Available Abstract Calcium phosphate is the most important inorganic constituent of biological tissues, and synthetic calcium phosphate has been widely used as biomaterials. In this study, a facile method has been developed for the fabrication of amorphous calcium phosphate (ACP/polylactide-block-monomethoxy(polyethyleneglycol hybrid nanoparticles and ACP porous nanospheres. Europium-doping is performed to enable photoluminescence (PL function of ACP porous nanospheres. A high specific surface area of the europium-doped ACP (Eu3+:ACP porous nanospheres is achieved (126.7 m2/g. PL properties of Eu3+:ACP porous nanospheres are investigated, and the most intense peak at 612 nm is observed at 5 mol% Eu3+ doping. In vitro cytotoxicity experiments indicate that the as-prepared Eu3+:ACP porous nanospheres are biocompatible. In vitro drug release experiments indicate that the ibuprofen-loaded Eu3+:ACP porous nanospheres show a slow and sustained drug release in simulated body fluid. We have found that the cumulative amount of released drug has a linear relationship with the natural logarithm of release time (ln(t. The Eu3+:ACP porous nanospheres are bioactive, and can transform to hydroxyapatite during drug release. The PL properties of drug-loaded nanocarriers before and after drug release are also investigated.

  17. Europium-doped amorphous calcium phosphate porous nanospheres: preparation and application as luminescent drug carriers

    Science.gov (United States)

    Chen, Feng; Zhu, Ying-Jie; Zhang, Kui-Hua; Wu, Jin; Wang, Ke-Wei; Tang, Qi-Li; Mo, Xiu-Mei

    2011-12-01

    Calcium phosphate is the most important inorganic constituent of biological tissues, and synthetic calcium phosphate has been widely used as biomaterials. In this study, a facile method has been developed for the fabrication of amorphous calcium phosphate (ACP)/polylactide-block-monomethoxy(polyethyleneglycol) hybrid nanoparticles and ACP porous nanospheres. Europium-doping is performed to enable photoluminescence (PL) function of ACP porous nanospheres. A high specific surface area of the europium-doped ACP (Eu3+:ACP) porous nanospheres is achieved (126.7 m2/g). PL properties of Eu3+:ACP porous nanospheres are investigated, and the most intense peak at 612 nm is observed at 5 mol% Eu3+ doping. In vitro cytotoxicity experiments indicate that the as-prepared Eu3+:ACP porous nanospheres are biocompatible. In vitro drug release experiments indicate that the ibuprofen-loaded Eu3+:ACP porous nanospheres show a slow and sustained drug release in simulated body fluid. We have found that the cumulative amount of released drug has a linear relationship with the natural logarithm of release time ( ln( t)). The Eu3+:ACP porous nanospheres are bioactive, and can transform to hydroxyapatite during drug release. The PL properties of drug-loaded nanocarriers before and after drug release are also investigated.

  18. Hydroxyapatite nanorod-assembled porous hollow polyhedra as drug/protein carriers.

    Science.gov (United States)

    Yu, Ya-Dong; Zhu, Ying-Jie; Qi, Chao; Jiang, Ying-Ying; Li, Heng; Wu, Jin

    2017-06-15

    Hydroxyapatite (HAP) with a porous hollow structure is an ideal biomaterial owing to its excellent biocompatibility and unique architecture. In this study, HAP nanorod-assembled porous hollow polyhedra, consisting of nanorod building blocks, have been successfully prepared at room temperature or under hydrothermal circumstances using a self-sacrificing Ca(OH) 2 template strategy. The hydrothermal treatment (at 180°C for 1h) can promote the HAP nanorods to be arranged with their axial direction normal to the polyhedron surface. The HAP nanorod-assembled porous hollow polyhedra have been explored for the potential application in drug/protein delivery, using ibuprofen (IBU) as a model drug and hemoglobin (Hb) as a model protein. The experimental results indicate that the HAP nanorod-assembled porous hollow polyhedra have a relatively high drug loading capacity and protein adsorption ability, and sustained drug and protein release. The HAP nanorod-assembled porous hollow polyhedra have promising applications in various biomedical fields such as the drug and protein delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Fabrication of drug-loaded edible carrier substrates from nanosuspensions by flexographic printing.

    Science.gov (United States)

    Palo, Mirja; Kolakovic, Ruzica; Laaksonen, Timo; Määttänen, Anni; Genina, Natalja; Salonen, Jarno; Peltonen, Jouko; Sandler, Niklas

    2015-10-30

    The main goal of the current work was to investigate the possible use of flexographic printing for the conversion of nanosuspensions into solid dosage forms. Aqueous nanosuspensions of indomethacin (IND) and itraconazole (ITR) with Poloxamer 407 as the stabilizer agent were prepared by wet ball-milling. The nanosuspensions were flexographically printed on three different substrates, including two commercially available edible substrates. The printed formulations were characterized with X-ray diffractometry (XRD) and scanning electron microscopy (SEM). In addition, dissolution studies for the printed IND and ITR formulations were conducted. The mean particle size of milled nanosuspensions of IND and ITR was 422.6 ± 7.7 nm and 698.1 ± 14.0 nm, respectively. The SEM imaging showed even distribution of nanosuspensions on the substrates after printing without any evident agglomeration. The printed formulations contained drug at least partially in crystalline form. The drug dissolution rate from the prepared formulations was improved compared to the pure drug. The drug release from the preparations on edible substrates was slightly slower due to the incorporation of the drug particles into the substrate matrix. In conclusion, the results indicated that flexographic printing can be considered as a promising fabrication method of solid nanoparticulate systems with enhanced dissolution behavior. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices

    DEFF Research Database (Denmark)

    Genina, Natalja; Hollander, Jenny; Jukarainen, Harri

    2016-01-01

    The main purpose of this work was to investigate the printability of different grades of ethylene vinyl acetate (EVA) copolymers as new feedstock material for fused-deposition modeling (FDM™)-based 3D printing technology in fabrication of custom-made T-shaped intrauterine systems (IUS) and subcut......The main purpose of this work was to investigate the printability of different grades of ethylene vinyl acetate (EVA) copolymers as new feedstock material for fused-deposition modeling (FDM™)-based 3D printing technology in fabrication of custom-made T-shaped intrauterine systems (IUS......) and subcutaneous rods (SR). The goal was to select an EVA grade with optimal properties, namely vinyl acetate content, melting index, flexural modulus, for 3D printing of implantable prototypes with the drug incorporated within the entire matrix of the medical devices. Indomethacin was used as a model drug...

  1. Aerodynamic Factors Responsible for the Deaggregation of Carrier-Free Drug Powders to form Micrometer and Submicrometer Aerosols

    Science.gov (United States)

    Longest, P. Worth; Son, Yoen-Ju; Holbrook, Landon; Hindle, Michael

    2013-01-01

    Purpose The objective of this study was to employ in vitro experiments combined with computational fluid dynamics (CFD) analysis to determine which aerodynamic factors were most responsible for deaggregating carrier-free powders to form micrometer and submicrometer aerosols from a capsule-based platform. Methods Eight airflow passages were evaluated for deaggregation of the aerosol including a standard constricted tube, impaction surface, 2D mesh, inward radial jets, and newly proposed 3D grids and rod arrays. CFD simulations were implemented to evaluate existing and new aerodynamic factors for deaggregation and in vitro experiments were used to evaluate performance of each inhaler. Results For the carrier-free formulation considered, turbulence was determined to be the primary deaggregation mechanism. A strong quantitative correlation was established between the mass median diameter (MMD) and newly proposed non-dimensional specific dissipation (NDSD) factor, which accounts for turbulent energy, inverse of the turbulent length scale, and exposure time. A 3D rod array design with unidirectional elements maximized NDSD and produced the best deaggregation with MMD<1μm. Conclusions The new NDSD parameter can be used to develop highly effective dry powder inhalers like the 3D rod array that can efficiently produce submicrometer aerosols for next-generation respiratory drug delivery applications. PMID:23471640

  2. Gelucire Based In Situ Gelling Emulsions: A Potential Carrier for Sustained Stomach Specific Delivery of Gastric Irritant Drugs

    Directory of Open Access Journals (Sweden)

    Ashwin Saxena

    2013-01-01

    Full Text Available Non steroidal anti-inflammatory drugs (NSAIDs are commonly prescribed medications to the geriatric patients for the treatment of arthritis and other painful disorders. The major side effects of NSAIDs are related to their effects on the stomach and bowels. The present study concerns assessment of the potential of liquid in situ gelling emulsion formulations (emulgels as patient compliant stomach specific sustained release carrier for the delivery of highly gastric irritant drug, Piroxicam. Emulgels were prepared, without using any emulgent, by mixing different concentrations of molten Gelucire 39/01 with low viscosity sodium alginate solution prepared in deionized water at 50°C. CaCO3 was used as buoyancy imparting as well as crosslinking agent. Emulgels so prepared were homogenous, physically stable, and rapidly formed into buoyant gelled mass when exposed to simulated gastric fluid (SGF, pH 1.2. Drug release studies carried out in SGF revealed significant retardation (P<0.05 of Piroxicam release from emulgels compared to conventional in situ gelling formulations prepared without Gelucire 39/01. Pharmacodynamic studies carried out in albino rats revealed significantly increased analgesic/anti-inflammatory response from in situ emulgels compared to conventional in situ gelling formulations. Further, in vivo toxicity studies carried out in albino rats revealed no signs of gastric ulceration upon prolonged dosing.

  3. Physicochemical characterisation and investigation of the bonding mechanisms of API-titanate nanotube composites as new drug carrier systems.

    Science.gov (United States)

    Sipos, Barbara; Pintye-Hódi, Klára; Kónya, Zoltán; Kelemen, András; Regdon, Géza; Sovány, Tamás

    2017-02-25

    Titanate nanotube (TNT) has recently been explored as a new carrier material for active pharmaceutical ingredients (API). The aim of the present work was to reveal the physicochemical properties of API-TNT composites, focusing on the interactions between the TNTs and the incorporated APIs. Drugs belonging to different Biopharmaceutical Classification System (BCS) classes were loaded into TNTs: diltiazem hydrochloride (BCS I.), diclofenac sodium (BCS II.), atenolol (BCS III.) and hydrochlorothiazide (BCS IV.). Experimental results demonstrated that it is feasible for spiral cross-sectioned titanate nanotubes to carry drugs and maintain their bioactivity. The structural properties of the composites were characterized by a range of analytical techniques, including FT-IR, DSC, TG-MS, etc. The interactions between APIs and TNTs were identified as electrostatic attractions, mainly dominated by hydrogen bonds. Based on the results, it can be stated that the strength of the association depends on the hydrogen donor strength of the API. The drug release of incorporated APIs was evaluated from compressed tablets and compared to that of pure APIs. Differences noticed in the dissolution profiles due to incorporation showed a correlation with the strength of interactions between the APIs and the TNTs observed in the above analytical studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Soluplus Graft Copolymer: Potential Novel Carrier Polymer in Electrospinning of Nanofibrous Drug Delivery Systems for Wound Therapy

    Science.gov (United States)

    Tamm, Ingrid; Laidmäe, Ivo; Lust, Andres; Kirsimäe, Kalle

    2014-01-01

    Electrospinning is an effective method in preparing polymeric nanofibrous drug delivery systems (DDSs) for topical wound healing and skin burn therapy applications. The aim of the present study was to investigate a new synthetic graft copolymer (Soluplus) as a hydrophilic carrier polymer in electrospinning of nanofibrous DDSs. Soluplus (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PCL-PVAc-PEG)) was applied in the nonwoven nanomats loaded with piroxicam (PRX) as a poorly water-soluble drug. Raman spectroscopy, X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy (SEM) were used in the physical characterization of nanofibrous DDSs. According to the SEM results, the drug-loaded PCL-PVAc-PEG nanofibers were circular in cross-section with an average diameter ranging from 500 nm up to 2 µm. Electrospinning stabilized the amorphous state of PRX. In addition, consistent and sustained-release profile was achieved with the present nanofibrous DDSs at the physiologically relevant temperature and pH applicable in wound healing therapy. In conclusion, electrospinning can be used to prepare nanofibrous DDSs of PCL-PVAc-PEG graft copolymer (Soluplus) and to stabilize the amorphous state of a poorly water-soluble PRX. The use of this synthetic graft copolymer can open new options to formulate nanofibrous DDSs for wound healing. PMID:24575414

  5. Biodegradable Poly (Lactic-co-Glycolic Acid)-Polyethylene Glycol Nanocapsules: An Efficient Carrier for Improved Solubility, Bioavailability, and Anticancer Property of Lutein.

    Science.gov (United States)

    Arunkumar, Ranganathan; Prashanth, Keelara Veerappa Harish; Manabe, Yuki; Hirata, Takashi; Sugawara, Tatsuya; Dharmesh, Shylaja Mallaiah; Baskaran, Vallikannan

    2015-06-01

    Lutein bioavailability is limited because of its poor aqueous solubility. In this study, lutein-poly (lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG) nanocapsules were prepared to improve the solubility, bioavailability, and anticancer property of lutein. The scanning electron microscopy and dynamic light scattering examination revealed that the nanocapsules are smooth and spherical with size ranging from 80 to 500 nm (mean = 200 nm). In vitro lutein release profile from nanocapsules showed controlled sustainable release (66%) up to 72 h. Aqueous solubility of lutein nanocapsules was much higher by 735-fold than the lutein. Fourier transform infrared spectroscopy analyses showed no chemical interaction among PLGA, PEG, and lutein, indicating possible weak intermolecular forces like hydrogen bonds. X-ray diffraction revealed lutein is distributed in a disordered amorphous state in nanocapsules. Postprandial plasma kinetics (area under the curve) of an oral dose of lutein from nanocapsules was higher by 5.4-fold compared with that of micellar lutein (control). The antiproliferative effect of lutein from nanocapsules (IC50 value, 10.9 μM) was higher (43.6%) than the lutein (IC50 value, 25 μM). Results suggest that PLGA-PEG nanocapsule is an efficient carrier for enhancing hydrophilicity, bioavailability, and anticancer property of lipophilic molecules such as lutein. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. New Ways of Imaging Uptake and Intracellular Fate of Liposomal Drug Carrier Systems inside Individual Cells, Based on Raman Microscopy

    Science.gov (United States)

    Matthäus, Christian; Kale, Amit; Chernenko, Tatyana; Torchilin, Vladimir; Diem, Max

    2009-01-01

    Recent developments, combining Raman spectroscopy with optical microscopy, provide a new noninvasive technique to assess and image cellular processes. Of particular interest are the uptake mechanisms of various cytologically active compounds. In order to distinguish the species of interest from their cellular environment spectroscopically, compounds may be labeled with deuterium. Here, we apply Raman microspectroscopy to follow the uptake of liposomal drug carrier systems that have been introduced to deliver biologically active compounds to their site of action within human breast adenocarcinoma MCF-7 cells. The distribution patterns of liposomes and liposomes surface-modified with a cell-penetrating peptide (TAT-peptide, TATp) have been imaged over time. The spectroscopic information obtained provides a clear evidence for variable rates, as well as different efficiencies of liposome uptake depending on their surface properties. Depending on the experimental setup, the technique may be applied to fixed or living cell organisms. PMID:18197626

  7. Coatless alginate pellets as sustained-release drug carrier for inflammatory bowel disease treatment.

    Science.gov (United States)

    Md Ramli, Siti Hajar; Wong, Tin Wui; Naharudin, Idanawati; Bose, Anirbandeep

    2016-11-05

    Conventional alginate pellets underwent rapid drug dissolution and failed to exert colon targeting unless subjected to complex coating. This study designed coatless delayed-release oral colon-specific alginate pellets for ulcerative colitis treatment. Alginate pellets, formulated with water-insoluble ethylcellulose and various calcium salts, were prepared using solvent-free melt pelletization technique which prevented reaction between processing materials during agglomeration and allowed reaction to initiate only in dissolution. Combination of acid-soluble calcium carbonate and highly water-soluble calcium acetate did not impart colon-specific characteristics to pellets due to pore formation in fragmented matrices. Combination of moderately water-soluble calcium phosphate and calcium acetate delayed drug release due to rapid alginate crosslinking by soluble calcium from acetate salt followed by sustaining alginate crosslinking by calcium phosphate. The use of 1:3 ethylcellulose-to-alginate enhanced the sustained drug release attribute. The ethylcellulose was able to maintain the pellet integrity without calcium acetate. Using hydrophobic prednisolone as therapeutic, hydrophilic alginate pellets formulated with hydrophobic ethylcellulose and moderately polar calcium phosphate exhibited colon-specific in vitro drug release and in vivo anti-inflammatory action. Coatless oral colon-specific alginate pellets can be designed through optimal formulation with melt pelletization as the processing technology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Mechanism and kinetics of the loss of poorly soluble drugs from liposomal carriers studied by a novel flow field-flow fractionation-based drug release-/transfer-assay

    DEFF Research Database (Denmark)

    Hinna, Askell Hvid; Hupfeld, Stefan; Kuntsche, Judith

    2016-01-01

    Liposomes represent a versatile drug formulation approach e.g. for improving the water-solubility of poorly soluble drugs but also to achieve drug targeting and controlled release. For the latter applications it is essential that the drug remains associated with the liposomal carrier during transit...... in the vascular bed. A range of in vitro test methods has been suggested over the years for prediction of the release of drug from liposomal carriers. The majority of these fail to give a realistic prediction for poorly water-soluble drugs due to the intrinsic tendency of such compounds to remain associated......)21H,23H-porphine). p-THPP is structurally similar to temoporfin, a photosensitizer which is under clinical evaluation in a liposomal formulation. Mechanistic insights were gained by varying the donor-to-acceptor lipid mass ratio, size and lamellarity of the liposomes. Drug transfer kinetics from one...

  9. Comparison of 3 biodegradable polymer and durable polymer-based drug-eluting stents in all-comers (BIO-RESORT): Rationale and study design of the randomized TWENTE III multicenter trial

    NARCIS (Netherlands)

    Lam, Ming Kai; Sen, Hanim; Sen, Hanim; Tandjung, K.; Tandjung, K.; van Houwelingen, K. Gert; de Vries, Arie G.; Danse, Peter W.; Schotborgh, Carl E.; Scholte, Martijn; Löwik, Marije M.; Linssen, Gerard C.M.; IJzerman, Maarten Joost; van der Palen, Jacobus Adrianus Maria; Doggen, Catharina Jacoba Maria; von Birgelen, Clemens

    2014-01-01

    Aim To evaluate the safety and efficacy of 2 novel drug-eluting stents (DES) with biodegradable polymer-based coatings versus a durable coating DES. Methods and Results BIO-RESORT is an investigator-initiated, prospective, patient-blinded, randomized multicenter trial in 3540 Dutch all-comers with

  10. Smart Carriers and Nanohealers: A Nanomedical Insight on Natural Polymers

    Directory of Open Access Journals (Sweden)

    Sreejith Raveendran

    2017-08-01

    Full Text Available Biodegradable polymers are popularly being used in an increasing number of fields in the past few decades. The popularity and favorability of these materials are due to their remarkable properties, enabling a wide range of applications and market requirements to be met. Polymer biodegradable systems are a promising arena of research for targeted and site-specific controlled drug delivery, for developing artificial limbs, 3D porous scaffolds for cellular regeneration or tissue engineering and biosensing applications. Several natural polymers have been identified, blended, functionalized and applied for designing nanoscaffolds and drug carriers as a prerequisite for enumerable bionano technological applications. Apart from these, natural polymers have been well studied and are widely used in material science and industrial fields. The present review explains the prominent features of commonly used natural polymers (polysaccharides and proteins in various nanomedical applications and reveals the current status of the polymer research in bionanotechnology and science sectors.

  11. Natural gums as sustained release carriers: development of gastroretentive drug delivery system of ziprasidone HCl

    Directory of Open Access Journals (Sweden)

    AJ Rajamma

    2012-10-01

    Full Text Available Abstract Background Objective of this study is to show the potential use of natural gums in the development of drug delivery systems. Therefore in this work gastro retentive tablet formulations of ziprasidone HCl were developed using simplex lattice design considering concentration of okra gum, locust bean gum and HPMC K4M as independent variables. A response surface plot and multiple regression equations were used to evaluate the effect of independent variables on hardness, flag time, floating time and drug release for 1 h, 2 h, and 8 h and for 24 h. A checkpoint batch was also prepared by considering the constraints and desirability of optimized formulation to improve its in vitro performance. Significance of result was analyzed using ANOVA and p was considered statistically significant. Results Formulation chiefly contains locust bean gum found to be favorable for hardness and floatability but combined effect of three variables was responsible for the sustained release of drug. The in vitro drug release data of check point batch (F8 was found to be sustained well compared to the most satisfactory formulation (F7 of 7 runs. The ‘n’ value was found to be between 0.5 and 1 suggesting that release of drug follows anomalous (non-fickian diffusion mechanism indicating both diffusion and erosion mechanism from these natural gums. Predicted results were almost similar to the observed experimental values indicating the accuracy of the design. In vivo floatability test indicated non adherence to the gastric mucosa and tablets remain buoyant for more than 24 h. Conclusions Study showed these eco-friendly natural gums can be considered as promising SR polymers.

  12. Self-Assembled Cationic Biodegradable Nanoparticles from pH-Responsive Amino-Acid-Based Poly(Ester Urea Urethane)s and Their Application As a Drug Delivery Vehicle.

    Science.gov (United States)

    He, Mingyu; Potuck, Alicia; Kohn, Julie C; Fung, Katharina; Reinhart-King, Cynthia A; Chu, Chih-Chang

    2016-02-08

    The objective of this study is to develop a new family of biodegradable and biologically active copolymers and their subsequent self-assembled cationic nanoparticles as better delivery vehicles for anticancer drugs to achieve the synergism between the cytotoxicity effects of the loaded drugs and the macrophage inflammatory response of the delivery vehicle. This family of cationic nanoparticles was formulated from a new family of amphiphilic cationic Arginine-Leucine (Arg-Leu)-based poly(ester urea urethane) (Arg-Leu PEUU) synthesized from four building blocks (amino acids, diols, glycerol α-monoallyl ether, and 1,6 hexamethylene diisocyanate). The chemical, physical, and biological properties of Arg-Leu PEUU biomaterials can be tuned by controlling the feed ratio of the four building blocks. The Arg-Leu PEUU copolymers have weight-average molecular weights from 13.4 to 16.8 kDa and glass-transition temperatures from -3.4 to -4.6 °C. The self-assembled cationic nanoparticles (Arg-Leu PEUU NPs) were prepared using a facile dialysis method. Arg-Leu PEUU NPs have average diameters ranging from 187 to 272 nm, show good biocompatibility with 3T3 fibroblasts, and they support bovine aortic endothelial cell (BAEC) proliferation and adhesion. Arg-Leu PEUU NPs also enhanced the macrophages' production of tumor necrosis factor-α (TNF-α) and nitric oxide (NO), but produced relatively low levels of interleukin-10 (IL-10), and therefore, the antitumor activity of macrophages might be enhanced. Arg-Leu PEUU NPs were taken up by HeLa cells after 4 h of incubation. The in vitro hemolysis assay showed the cationic Arg-Leu PEUU NPs increased their chance of endosomal escape at a more acidic pH. Doxorubicin (DOX) was successfully incorporated into the Arg-Leu PEUU NPs, and the DOX-loaded Arg-Leu PEUU NPs exhibited a pH-dependent drug release profile with accelerated release kinetics in a mild acidic condition. The DOX-loaded 6-Arg-4-Leu-4 A/L-2/1 NPs showed higher HeLa cell

  13. Selective Release of anti–TB Drugs Complex from Smart Copolymeric Bioactive nano–carriers

    Directory of Open Access Journals (Sweden)

    Alejandro Arredondo–Peñaranda

    2014-07-01

    Full Text Available Smart nano–copolymeric matrices have been employed to load and release anti tuberculosis (anti – TB drugs combinated complexes of Ethambutol (EMB, Isoniazid (INH, Rifampicin (RMP and Pyrazinamide (PZA. Copolymeric nanocarriers were synthesized using a microemulsion polymerization method previously reported. These nanocarriers can show selective swelling–collapse response under changes in local environments such a temperature, pH, solvent composition and electrical stimuli. The employ of these kinds of systems permits a controlled and selective delivery and release on specific human tissues. High Performance Liquid Chromatography technique was used to allow the detection of combinated mixtures of different active principles of anti–TB drugs using an acetonitrile mobile phase at 0.5 mL/min of flow rate whit a Spherisorb ODS2, C18 column. The results obtained suggest that the employ of smart nanohydrogels is a novel method in several tuberculosis therapies.

  14. Impact of speciation on the electron charge transfer properties of nanodiamond drug carriers.

    Science.gov (United States)

    Sun, Baichuan; Barnard, Amanda S

    2016-08-07

    Unpassivated diamond nanoparticles (bucky-diamonds) exhibit a unique surface reconstruction involving graphitization of certain crystal facets, giving rise to hybrid core-shell particles containing both aromatic and aliphatic carbon. Considerable effort is directed toward eliminating the aromatic shell, but persistent graphitization of subsequent subsurface-layers makes perdurable purification a challenge. In this study we use some simple statistical methods, in combination with electronic structure simulations, to predict the impact of different fractions of aromatic and aliphatic carbon on the charge transfer properties of the ensembles of bucky-diamonds. By predicting quality factors for a variety of cases, we find that perfect purification is not necessary to preserve selectivity, and there is a clear motivation for purifying samples to improve the sensitivity of charge transfer reactions. This may prove useful in designing drug delivery systems where the release of (selected) drugs needs to be sensitive to specific conditions at the point of delivery.

  15. Nanosuspensions as a versatile carrier based drug delivery system--an overview.

    Science.gov (United States)

    Sudhakar, Beeravelli; NagaJyothi, Kothagunda; Murthy, K V Ramana

    2014-01-01

    Nanotechnology is being explored in many ways to design a new chemical entity (NCE) to an active pharmaceutical ingredient (API). Of the different nanotechnologies, Nanosuspensions has gained a lot of interest due to its ease of production and applicability to a large number of drugs. This present review article on nanosuspensions is focused on the various principles, production techniques, stability problems, various marketed formulations and current trends associated with the nanosuspensions.

  16. Propylene glycol-embodying deformable liposomes as a novel drug delivery carrier for vaginal fibrauretine delivery applications.

    Science.gov (United States)

    Li, Wei-Ze; Hao, Xu-Liang; Zhao, Ning; Han, Wen-Xia; Zhai, Xi-Feng; Zhao, Qian; Wang, Yu-E; Zhou, Yong-Qiang; Cheng, Yu-Chuan; Yue, Yong-Hua; Fu, Li-Na; Zhou, Ji-Lei; Wu, Hong-Yu; Dong, Chun-Jing

    2016-03-28

    . These results indicate that the propylene glycol-embodying deformable liposomes may be a promising drug delivery carrier for vaginal delivery of fibrauretine. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Hydrophobically modified polysaccharide-based on polysialic acid nanoparticles as carriers for anticancer drugs.

    Science.gov (United States)

    Jung, Bom; Shim, Man-Kyu; Park, Min-Ju; Jang, Eun Hyang; Yoon, Hong Yeol; Kim, Kwangmeyung; Kim, Jong-Ho

    2017-03-30

    This study presented the development of hydrophobically modified polysialic acid (HPSA) nanoparticles, a novel anticancer drug nanocarrier that increases therapeutic efficacy without causing nonspecific toxicity towards normal cells. HPSA nanoparticles were prepared by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC)/N-hydroxysuccinimide (NHS) coupling between N-deacetylated polysialic acid (PSA) and 5β-cholanic acid. The physicochemical characteristics of HPSA nanoparticles (zeta-potential, morphology and size) were measured, and in vitro cytotoxicity and cellular uptake of PSA and HPSA nanoparticles were tested in A549 cells. In vivo cancer targeting of HPSA nanoparticles was evaluated by labeling PSA and HPSA nanoparticles with Cy5.5, a near-infrared fluorescent dye, for imaging. HPSA nanoparticles showed improved cancer-targeting ability compared with PSA. Doxorubicin-loaded HPSA (DOX-HPSA) nanoparticles were prepared using a simple dialysis method. An analysis of the in vitro drug-release profile and drug-delivery behavior showed that DOX was effectively released from DOX-HPSA nanoparticles. In vivo cancer therapy with DOX-HPSA nanoparticles in mice showed antitumor effects that resembled those of free DOX. Moreover, DOX-HPSA nanoparticles had low toxicity toward other organs, reflecting their tumor-targeting property. Hence, HPSA nanoparticles are considered a potential nanocarrier for anticancer agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Evaluation of brain targeting and mucosal integrity of nasally administrated nanostructured carriers of a CNS active drug, clonazepam.

    Science.gov (United States)

    Abdel-Bar, Hend Mohamed; Abdel-Reheem, Amal Youssef; Awad, Gehanne Abdel Samie; Mortada, Nahed Daoud

    2013-01-01

    The aim of the study was to target clonazepam, a CNS active drug, to the brain through the non-invasive intranasal (in) route using of nanocarriers with proven safety in clonazepam nanocarriers were prepared by mixing isopropyl myristate, Tween 80, Cremophor EL or lecithin, polyethylene glycol 200, propylene glycol or ethanol in different ratios with water. in-vitro characterization of the nanocarriers was done by various methods including: polarized light microscopy, particle size determination, viscosity measurements and drug release studies. in-vivo study comparing intranasal and intravenous administration was performed. The drug targeting efficiency (DTE %) and direct nose to brain transport percentage (DTP %) were calculated and nasal integrity assessment was carried out. The obtained formulae had particle size below 100 nm favoring rapid direct nose to brain transport and the time for 100% drug release (T100%) depended on systems composition. Plasma Tmax of clonazepam nanostructured carriers varied from 10-30 min., while their brain Tmax did not exceed 10 min, in comparison with 30 min for iv solution. Although there was no significant difference (p>0.05) between the plasma AUC0-∞ of the different tested nanocarriers and intravenous one, the increase in brain AUC 0 -∞ of different nasal formulations in comparison to that of iv administration (3.6 -7.2 fold) confirms direct nose to brain transport via olfactory region. Furthermore, DTE and DTP% confirmed brain targeting of clonazepam following intranasal administration. The results confirmed that intranasal nanocarriers were proved to be safe alternative for iv clonazepam delivery with rapid nose to brain transport.

  19. Optimization and design of ibuprofen-loaded nanostructured lipid carriers using a hybrid-design approach for ocular drug delivery

    Science.gov (United States)

    Rathod, Vishal

    The objective of the present project was to develop the Ibuprofen-loaded Nanostructured Lipid Carrier (IBU-NLCs) for topical ocular delivery based on substantial pre-formulation screening of the components and understanding the interplay between the formulation and process variables. The BCS Class II drug: Ibuprofen was selected as the model drug for the current study. IBU-NLCs were prepared by melt emulsification and ultrasonication technique. Extensive pre-formulation studies were performed to screen the lipid components (solid and liquid) based on drug's solubility and affinity as well as components compatibility. The results from DSC & XRD assisted in selecting the most suitable ratio to be utilized for future studies. DynasanRTM 114 was selected as the solid lipid & MiglyolRTM 840 was selected as the liquid lipid based on preliminary lipid screening. The ratio of 6:4 was predicted to be the best based on its crystallinity index and the thermal events. As there are many variables involved for further optimization of the formulation, a single design approach is not always adequate. A hybrid-design approach was applied by employing the Plackett Burman design (PBD) for preliminary screening of 7 critical variables, followed by Box-Behnken design (BBD), a sub-type of response surface methodology (RSM) design using 2 relatively significant variables from the former design and incorporating Surfactant/Co-surfactant ratio as the third variable. Comparatively, KolliphorRTM HS15 demonstrated lower Mean Particle Size (PS) & Polydispersity Index (PDI) and KolliphorRTM P188 resulted in Zeta Potential (ZP) ibuprofen thereafter over several hours. These values also confirm that the production method, and all other selected variables, effectively promoted the incorporation of ibuprofen in NLC. Quality by Design (QbD) approach was successfully implemented in developing a robust ophthalmic formulation with superior physicochemical and morphometric properties. NLCs as the

  20. Oil-in-water biocompatible microemulsion as a carrier for the antitumor drug compound methyl dihydrojasmonate

    Directory of Open Access Journals (Sweden)

    Silva GB

    2015-01-01

    Full Text Available Gisela Bevilacqua Rolfsen Ferreira da Silva,1 Maria Virginia Scarpa,1 Iracilda Zepone Carlos,2 Marcela Bassi Quilles,2 Raphael Carlos Comeli Lia,3 Eryvaldo Socrates Tabosa do Egito,4 Anselmo Gomes de Oliveira1 1Departamento de Fármacos e Medicamentos, 2Departamento de Análises Clínicas, UNESP–Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, PPG em Nanotecnologia Farmacêutica, Rodovia Araraquara-Jaú Km 01, Araraquara, SP, Brazil; 3Instituto de Patologia Cirúrgica e Citopatologia (IPC, Araraquara, SP, Brazil; 4UFRN–Universidade Federal do Rio Grande do Norte, Programa de Pós-graduação em Ciências da Saúde, Natal, RN, Brazil Abstract: Methyl dihydrojasmonate (MJ has been studied because of its application as an antitumor drug compound. However, as MJ is a poorly water-soluble compound, a suitable oil-in-water microemulsion (ME has been studied in order to provide its solubilization in an aqueous media and to allow its administration by the parenteral route. The ME used in this work was characterized on the pseudo-ternary phase diagram by dynamic light scattering and rheological measurements. Regardless of the drug presence, the droplet size was directly dependent on the oil/surfactant (O/S ratio. Furthermore, the drug incorporation into the ME significantly increased the ME diameter, mainly at low O/S ratios. The rheological evaluation of the systems showed that in the absence of drug a Newtonian behavior was observed. On the other hand, in the presence of MJ the ME systems revealed pseudoplastic behavior, independently of the O/S ratio. The in vivo studies demonstrated that not only was the effect on the tumor inhibition inversely dependent on the MJ-loaded ME administered dose, but also it was slightly higher than the doxorubicin alone, which was used as the positive control. Additionally, a small antiangiogenic effect for MJ-loaded ME was found at doses in which it possesses antitumor activity. MJ revealed to

  1. Methods for synthesizing the macromolecular constituents of smart nanosized carriers for controlled drug delivery.

    Science.gov (United States)

    Balaure, Paul Catalin; Grumezescu, Alexandru Mihai

    2014-01-01

    Smart multifunctional polymeric nanocarriers able to respond to physicochemical changes in their environment or to external stimuli represent a new paradigm in the field of pharmaceutical formulations for controlled drug delivery. The introductory part of the present review deals with this new concept and presents the main advantages resulting from the use of such nanovehicles instead of conventional, much larger drug delivery systems. The access to drug nanocarriers based on smart supramolecular polymeric materials is primarily limited by the available polymerization methods capable to produce polymers with low polydispersity index, as well as much more complex macromolecular architectures with strictly controlled chemical composition, such as block copolymers and star or graft polymers or copolymers. This article reviews the state-of-the art in controlled/"living" free radical polymerization techniques as well as ring opening polymerization methods. Nitroxide mediated free radical polymerization (NMP), atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain-transfer polymerization (RAFT), single electron transfer-living radical polymerization (SET-LRP), single electron transfer-nitroxide radical coupling reaction (SET-NRC), cationic ring opening polymerization (CROP), anionic ring opening polymerization (AROP), and metal catalyzed ring opening polymerization are described, highlighting their mechanistic details and their synthetic potential as well as their limitations. The final part of the article is dedicated to a special type of unimolecular, monodisperse nanocarriers - the dendrimers. Both divergent and convergent approaches to dendrimer synthesis are described along with the therapeutic applications taking advantage of the unique branched tree-like globular structure of dendrimers to treat cancer.

  2. Nanostructures by self-assembling peptide amphiphile as potential selective drug carriers.

    Science.gov (United States)

    Accardo, Antonella; Tesauro, Diego; Mangiapia, Gaetano; Pedone, Carlo; Morelli, Giancarlo

    2007-01-01

    The self-assembling behavior, at physiological pH, of the amphiphile peptide (C18)(2)L5CCK8 in nanostructures is reported. Stable aggregates presenting a critical micellar concentration of 2 x 10(-6) mol kg(-1), and characterized by water exposed CCK8 peptide in beta-sheet conformation, are obtained. Small angle neutron scattering experiments are indicative for a 3D structure with dimensions > or =100 nm. AFM images confirm the presence of nanostructures. Fluorescence experiments indicating the sequestration of pyrene, chosen as drug model, and the anticancer Doxorubicin within the nanostructures are reported.

  3. Preparation, Characterization and Evaluation of α-Tocopherol Succinate-Modified Dextran Micelles as Potential Drug Carriers

    Directory of Open Access Journals (Sweden)

    Jingmou Yu

    2015-09-01

    Full Text Available In the present study, α-tocopherol succinate (TOS conjugated dextran (Dex-TOS was synthesized and characterized by fourier transform infrared (FT-IR spectroscopy, 1H nuclear magnetic resonance (1H NMR, dynamic light scattering (DLS and fluorescence spectroscopy. Dex-TOS could form nanoscaled micelles in aqueous medium. The critical micelle concentration (CMC is 0.0034 mg/mL. Doxorubicin (Dox was selected as a model drug. Dox-loaded Dex-TOS (Dex-TOS/Dox micelles were prepared by a dialysis method. The size of Dex-TOS/Dox micelles increased from 295 to 325 nm with the Dox-loading content increasing from 4.21% to 8.12%. The Dex-TOS/Dox micelles were almost spherical in shape, as determined by transmission electron microscopy (TEM. In vitro release demonstrated that Dox release from the micelles was in a sustained manner for up to 96 h. The cellular uptake of Dex-TOS/Dox micelles in human nasopharyngeal epidermoid carcinoma (KB cells is an endocytic process determined by confocal laser scanning microscopy (CLSM. Moreover, Dex-TOS/Dox micelles exhibited comparable cytotoxicity in contrast with doxorubicin hydrochloride. These results suggested that Dex-TOS micelles could be a promising carrier for drug delivery.

  4. Polymeric films as a promising carrier for bioadhesive drug delivery: Development, characterization and optimization

    Directory of Open Access Journals (Sweden)

    Pallavi Bassi

    2017-01-01

    Full Text Available Bioadhesive films using tamarind seed polysaccharide were prepared for the treatment of candida vaginitis using nystatin as the model drug. Films were prepared by solvent casting method. A 32 factorial design was employed to study the effect of independent variables (polymer and plasticizer concentration on a range of dependent variables namely mechanical, swelling, interfacial, and bioadhesive properties through response surface methodological approach, using Design Expert® software. Formulation composition that provided the most desired and optimized results was selected using desirability approach. Nystatin was solubilized using Tween 60 and was incorporated into the selected film. Drug solubilization and dispersion were confirmed by scanning electron microscopy and differential scanning calorimetry. The optimized film released 73.92 ± 2.54% of nystatin at the end of 8 h in simulated vaginal fluid and the release data showed best fit to Korsmeyer–Peppas model with R2 of 0.9990 and the release mechanism to be super case-II. The optimized film also showed appropriate anti candida activity through appearance of zone of inhibition during antifungal activity testing study.

  5. Self-assembled polymersomes conjugated with lactoferrin as novel drug carrier for brain delivery.

    Science.gov (United States)

    Yu, Yuan; Pang, Zhiqing; Lu, Wei; Yin, Qi; Gao, Huile; Jiang, Xinguo

    2012-01-01

    To develop a novel brain drug delivery system based on self-assembled poly(ethyleneglycol)-poly (D,L-lactic-co-glycolic acid) (PEG-PLGA) polymersomes conjugated with lactoferrin (Lf-POS). The brain delivery properties of Lf-POS were investigated and optimized. Three formulations of Lf-POS, with different densities of lactoferrin on the surface of polymersomes, were prepared and characterized. The brain delivery properties in mice were investigated using 6-coumarin as a fluorescent probe loaded in Lf-POS (6-coumarin-Lf-POS). A neuroprotective peptide, S14G-humanin, was incorporated into Lf-POS (SHN-Lf-POS); a protective effect on the hippocampuses of rats treated by Amyloid-β(25-35) was investigated by immunohistochemical analysis. The results of brain delivery in mice demonstrated that the optimized number of lactoferrin conjugated per polymersome was 101. This obtains the greatest blood-brain barrier (BBB) permeability surface area(PS) product and percentage of injected dose per gram brain (%ID/g brain). Immunohistochemistry revealed the SHN-Lf-POS had a protective effect on neurons of rats by attenuating the expression of Bax and caspase-3 positive cells. Meanwhile, the activity of choline acetyltransferase (ChAT) had been increased compared with negative controls. These results suggest that lactoferrin functionalized self-assembled PEG-PLGA polymersomes could be a promising brain-targeting peptide drug delivery system via intravenous administration.

  6. Aptamer-conjugated DNA nano-ring as the carrier of drug molecules

    Science.gov (United States)

    Srivithya, Vellampatti; Roun, Heo; Sekhar Babu, Mitta; Hyung, Park Jae; Ha, Park Sung

    2018-03-01

    Due to its predictable self-assembly and structural stability, structural DNA nanotechnology is considered one of the main interdisciplinary subjects encompassing conventional nanotechnology and biotechnology. Here we have fabricated the mucin aptamer (MUC1)˗conjugated DNA nano˗ring intercalated with doxorubicin (DNRA˗DOX) as potential therapeutics for breast cancer. DNRA˗DOX exhibited significantly higher cytotoxicity to the MCF˗7 breast cancer cells than the controls, including DOX alone and the aptamer deficient DNA nano˗ring (DNR) with doxorubicin. Interactions between DOX and DNRA were studied using spectrophotometric measurements. Dose-dependent cytotoxicity was performed to prove that both DNR and DNRA were non-toxic to the cells. The drug release profile showed a controlled release of DOX at normal physiological pH 7.4, with approximately 61% released, but when exposed to lysosomal of pH 5.5, the corresponding 95% was released within 48 h. Owing to the presence of the aptamer, DNRA˗DOX was effectively taken up by the cancer cells, as confirmed by confocal microscopy, implying that it has potential for use in targeted drug delivery.

  7. Experimental and theoretical evaluation of nanodiamonds as pH triggered drug carriers

    KAUST Repository

    Yan, Jingjing

    2012-01-01

    Nanodiamond (ND) and its derivatives have been widely used for drug, protein and gene delivery. Herein, experimental and theoretical methods have been combined to investigate the effect of pH on the delivery of doxorubicin (DOX) from fluorescein labeled NDs (Fc-NDs). In the endosomal recycling process, the nanoparticle will pass from mildly acidic vesicle to pH ≈ 4.8; thus, it is important to investigate DOX release from NDs at different pH values. Fc-NDs released DOX dramatically under acidic conditions, while an increase in the DOX loading efficiency (up to 6.4 wt%) was observed under basic conditions. Further theoretical calculations suggest that H + weakens the electrostatistic interaction between ND surface carboxyl groups and DOX amino groups, and the interaction energies at pH < 7, pH 7 and pH > 7 are 10.4 kcal mol -1, 25.0 kcal mol -1 and 27.0 kcal mol -1 respectively. Cellular imaging experiments show that Fc-NDs are readily ingested by breast adenocarcinoma (BA) cells and cell viability tests prove that they can be utilized as a safe drug delivery vehicle. Furthermore, pH triggered DOX release has been tested in vitro (pH 7.4 and pH 4.83) in breast adenocarcinoma (BA) cells. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2012.

  8. Transfer kinetics from colloidal drug carriers and liposomes to biomembrane models: DSC studies

    Directory of Open Access Journals (Sweden)

    Maria Grazia Sarpietro

    2011-01-01

    Full Text Available The release of bioactive molecules by different delivery systems has been studied. We have proposed a protocol that takes into account a system that is able to carry out the uptake of a bioactive molecule released during the time, resembling an in vivo-like system, and for this reason we have used biomembrane models represented by multi-lamellar and unilamellar vesicles. The bioactive molecule loaded delivery system has been put in contact with the biomembrane model and the release has been evaluated, to consider the effect of the bioactive molecule on the biomembrane model thermotropic behavior, and to compare the results with those obtained when a pure drug interacts with the biomembrane model. The differential scanning calorimetry technique has been employed. Depending on the delivery system used, our research permits to evaluate the effect of different parameters on the bioactive molecule release, such as pH, drug loading degree, delivery system swelling, crosslinking agent, degree of cross-linking, and delivery system side chains.

  9. Influence of emulsifiers on the characteristics of polyurethane structures used as drug carrier.

    Science.gov (United States)

    Heghes, Alina; Soica, Codruta M; Ardelean, Simona; Ambrus, Rita; Muntean, Danina; Galuscan, Atena; Dragos, Dan; Ionescu, Daniela; Borcan, Florin

    2013-04-10

    Emulsifiers have a significant role in the emulsion polymerization by reducing the interfacial tension thus increasing the stability of colloidal dispersions of polymer nanostructures. This study evaluates the impact of four emulsifiers on the characteristics of polyurethane hollow structures used as drug delivery system. Polyurethane (PU) structures with high stability and sizes ranging from nano- to micro-scale were obtained by interfacial polyaddition combined with spontaneous emulsification. The pH of PU aqueous solutions (0.1% w/w) was slightly acidic, which is acceptable for products intended to be used on human skin. Agglomerated structures with irregular shapes were observed by scanning electron microscopy. The synthesized structures have melting points between 245-265°C and reveal promising results in different evaluations (TEWL, mexametry) on murine skin. In this study hollow PU structures of reduced noxiousness were synthesized, their size and stability being influenced by emulsifiers. Such structures could be used in the pharmaceutical field as future drug delivery systems.

  10. In situ gel systems as 'smart' carriers for sustained ocular drug delivery.

    Science.gov (United States)

    Agrawal, Ashish Kumar; Das, Manasmita; Jain, Sanyog

    2012-04-01

    In situ gel systems refer to a class of novel delivery vehicles, composed of natural, semisynthetic or synthetic polymers, which present the unique property of sol-gel conversion on receipt of biological stimulus. The present review summarizes the latest developments in in situ gel technology, with regard to ophthalmic drug delivery. Starting with the mechanism of ocular absorption, the review expands on the fabrication of various polymeric in situ gel systems, made up of two or more polymers presenting multi-stimuli sensitivity, coupled with other interesting features, such as bio-adhesion, enhanced penetration or sustained release. Various key issues and challenges in this area have been addressed and critically analyzed. The advent of in situ gel systems has inaugurated a new transom for 'smart' ocular delivery. By virtue of possessing stimuli-responsive phase transition properties, these systems can easily be administered into the eye, similar to normal eye drops. Their unique gelling properties endow them with special features, such as prolonged retention at the site of administration, followed by sustained drug release. Despite the superiority of these systems as compared with conventional ophthalmic formulations, further investigations are necessary to address the toxicity issues, so as to minimize regulatory hurdles during commercialization.

  11. Hydrazone-bearing PMMA-functionalized magnetic nanocubes as pH-responsive drug carriers for remotely targeted cancer therapy in vitro and in vivo.

    Science.gov (United States)

    Ding, Xingwei; Liu, Yun; Li, Jinghua; Luo, Zhong; Hu, Yan; Zhang, Beilu; Liu, Junjie; Zhou, Jun; Cai, Kaiyong

    2014-05-28

    To develop vehicles for efficient chemotherapeutic cancer therapy, we report a remotely triggered drug delivery system based on magnetic nanocubes. The synthesized magnetic nanocubes with average edge length of around 30 nm acted as cores, whereas poly(methyl methacrylate) (PMMA) was employed as an intermediate coating layer. Hydrazide was then tailored onto PMMA both for doxorubicin (DOX) loading and pH responsive drug delivery via the breakage of hydrazine bonds. The successful fabrication of the pH responsive drug carrier was confirmed by transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and magnetic hysteresis loops, respectively. The carrier was stable at neutral environment and doxorubicin released at pH of 5.0. Cell viability assay and confocal laser scanning microscopy observations demonstrated that the loaded DOX could be efficiently released after cellular endocytosis and induced cancer cells apoptosis thereby. More importantly, the carrier could be guided to the tumor tissue site with an external magnetic field and led to efficient tumor inhibition with low side effects, which were reflected by magnetic resonance imaging (MRI), change of tumor size, TUNEL staining, and H&E staining assays, respectively. All results suggest that hydrazide-tailoring PMMA-coated magnetic nanocube would be a promising pH-responsive drug carrier for remotely targeted cancer therapy in vitro and in vivo.

  12. Assembled microcapsules by doxorubicin and polysaccharide as high effective anticancer drug carriers.

    Science.gov (United States)

    Du, Cuiling; Zhao, Jie; Fei, Jinbo; Cui, Yue; Li, Junbai

    2013-09-01

    Doxorubicin, together with the modified polysaccharide (alginate dialdehyde), was used as a wall material to fabricate microcapsules through self-cross-linking by a template method. The microcapsules as-prepared are pH-responsive. Relevant scanning electronic microscopy, atom force microscopy and confocal laser scanning microscopy confirm the morphology of the uniform microcapsules. The spectroscopic results show that the microcapsules are assembled through electrostatic interaction and Schiff's base covalent bonding. Doxorubicin can be released sustainably from the capsules in buffer solution at a lower pH value. The cellular uptake of the microcapsules and drug release induced by acidic microenvironment are time-dependent processes. The cell cytotoxicity experiments in vitro demonstrate that the doxorubicin-based microcapsules have high efficiency to kill the cancer cells. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Oil biodegradation

    NARCIS (Netherlands)

    Rahsepar, Shokouhalsadat; Langenhoff, Alette A.M.; Smit, Martijn P.J.; Eenennaam, van Justine S.; Murk, Tinka; Rijnaarts, Huub H.M.

    2017-01-01

    During the Deepwater Horizon (DwH) oil spill, interactions between oil, clay particles and marine snow lead to the formation of aggregates. Interactions between these components play an important, but yet not well understood, role in biodegradation of oil in the ocean water. The aim of this study

  14. Polímeros sintéticos biodegradáveis: matérias-primas e métodos de produção de micropartículas para uso em drug delivery e liberação controlada Biodegradable synthetic polymers: raw-materials and production methods of microparticles for drug delivery and controlled release

    Directory of Open Access Journals (Sweden)

    Patrícia Severino

    2011-01-01

    Full Text Available Micropartículas produzidas a partir de polímeros sintéticos têm sido amplamente utilizadas na área farmacêutica para encapsulação de princípios ativos. Essas micropartículas apresentam as vantagens de proteção do princípio ativo, mucoadesão e gastrorresistência, melhor biodisponibilidade e maior adesão do paciente ao tratamento. Além disso, utiliza menores quantidade de princípio ativo para obtenção do efeito terapêutico proporcionando diminuição dos efeitos adversos locais, sistêmicos e menor toxidade. Os polímeros sintéticos empregados na produção das micropartículas são classificados biodegradáveis ou não biodegradáveis, sendo os biodegradáveis mais utilizados por não necessitam ser removidos cirurgicamente após o término de sua ação. A produção das micropartículas poliméricas sintéticas para encapsulação tanto de ativos hidrofílicos quanto hidrofóbicos pode ser emulsificação por extração e/ou evaporação do solvente; coacervação; métodos mecânicos e estão revisados neste artigo evidenciando as vantagens, desvantagens e viabilidade de cada metodologia. A escolha da metodologia e do polímero sintético a serem empregados na produção desse sistema dependem da aplicação terapêutica requerida, bem como a simplicidade, reprodutibilidade e factibilidade do aumento de escala da produção.Microparticles produced from synthetic polymers have been widely used in the pharmaceutical field for encapsulation of drugs. These microparticles show several advantages such as drug protection, mucoadhesion, gastro-resistance, improved bioavailability and increased patient's compliance. In addition, it is possible to use lower amount of drug to achieve therapeutic efficiency with reduced local/systemic adverse side effects and low toxicity. Synthetic polymers used for the production of microparticles are classified as biodegradable or non-biodegradable, being the former more popular since these do

  15. 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.

  16. Evaluation of the Biodegradable Igaki-Tamai Scaffold After Drug-Eluting Balloon Treatment of De Novo Superficial Femoral Artery Lesions: The GAIA-DEB Study.

    Science.gov (United States)

    Werner, Martin; Schmidt, Andrej; Scheinert, Susanne; Banning-Eichenseer, Ursula; Ulrich, Matthias; Bausback, Yvonne; Steiner, Sabine; Scheinert, Dierk

    2016-02-01

    To evaluate the safety and efficacy of the Igaki-Tamai biodegradable scaffold after drug-eluting balloon (DEB) angioplasty in patients with occlusive superficial femoral artery (SFA) disease. A prospective, single-center, nonrandomized study enrolled 20 patients (mean age 66.7±11.6 years; 14 men) with symptomatic de novo SFA lesions undergoing angioplasty with the In.Pact Admiral paclitaxel-coated balloon and subsequent implantation of the Igaki-Tamai bioresorbable scaffold. All patients were claudicants. The average diameter stenosis was 89.7%, and the mean length was 43.6 mm. Clinical examinations with duplex sonography were performed after 1, 6, 9, and 12 months. The main study outcomes were technical success, restenosis, target lesion revascularization (TLR), ankle-brachial index (ABI) improvement, and changes in quality of life evaluated with the walking impairment questionnaire. Safety was assessed by monitoring the occurrence of adverse events. Angioplasty with a paclitaxel-coated balloon was performed in all patients, resulting in an average diameter stenosis of 24%. Subsequent implantation of the Igaki-Tamai scaffold reduced the average diameter stenosis to 3.5%. In the first 6 months, 2 cases of restenosis were reported, with no TLRs within that period. However, by the 12-month follow-up in 19 patients, 11 patients had lost in-stent patency. Among these patients, 8 had TLRs, which were the only adverse events recorded that were referable to the procedure. Quality-of-life assessments showed improvement in the majority of patients. The GAIA-DEB study shows that DEB treatment of the femoral artery prior to the implantation of the biodegradable Igaki-Tamai scaffold is safe. However, the antiproliferative actions of paclitaxel in the vessel wall were not effective in preventing restenosis. In-stent restenosis occurred predominantly after 6 months. © The Author(s) 2015.

  17. Can Platforms Affect the Safety and Efficacy of Drug-Eluting Stents in the Era of Biodegradable Polymers?: A Meta-Analysis of 34,850 Randomized Individuals.

    Science.gov (United States)

    Yan, Yun-Feng; Jiang, Long; Zhang, Ming-Duo; Li, Xin-He; Nie, Mao-Xiao; Feng, Ting-Ting; Zhao, Xin; Wang, Lu-Ya; Zhao, Quan-Ming

    2016-01-01

    In the era of bare metal stents (BMSs), alloys have been considered to be better materials for stent design than stainless steel. In the era of biodegradable polymer drug-eluting stents (BP-DESs), the safety and efficacy of BP-DESs with different metal platforms (stainless steel or alloys) have not yet been reported, although their polymers are eventually absorbed, and only the metal platforms remain in the body. This study sought to determine the clinical safety and efficacy of BP-DESs with different platforms compared with other stents (other DESs and BMSs). PubMed, Embase and Clinical Trials.gov were searched for randomized controlled trials (RCTs) that compared BP-DESs with other stents. After performing pooled analysis of BP-DESs and other stents, we performed a subgroup analysis using two classification methods: stent platform and follow-up time. The study characteristics, patient characteristics and clinical outcomes were abstracted. Forty RCTs (49 studies) comprising 34,850 patients were included. Biodegradable polymer stainless drug-eluting stents (BP-stainless DESs) were superior to the other stents [mainly stainless drug-eluting stents (DESs)] in terms of pooled definite/probable stent thrombosis (ST) (OR [95% CI] = 0.76[0.61-0.95], p = 0.02), long-term definite/probable ST (OR [95% CI] = 0.73[0.57-0.94], p = 0.01), very late definite/probable ST (OR [95% CI] = 0.56[0.33-0.93], p = 0.03) and long-term definite ST. BP-stainless DESs had lower rates of pooled, mid-term and long-term target vessel revascularization (TVR) and target lesion revascularization (TLR) than the other stainless DESs and BMSs. Furthermore, BP-stainless DESs were associated with lower rates of long-term death than other stainless DESs and lower rates of mid-term myocardial infarction than BMSs. However, only the mid-term and long-term TVR rates were superior in BP-alloy DESs compared with the other stents. Our results indirectly suggest that BP-stainless DESs may offer more benefits

  18. Can Platforms Affect the Safety and Efficacy of Drug-Eluting Stents in the Era of Biodegradable Polymers?: A Meta-Analysis of 34,850 Randomized Individuals.

    Directory of Open Access Journals (Sweden)

    Yun-Feng Yan

    Full Text Available In the era of bare metal stents (BMSs, alloys have been considered to be better materials for stent design than stainless steel. In the era of biodegradable polymer drug-eluting stents (BP-DESs, the safety and efficacy of BP-DESs with different metal platforms (stainless steel or alloys have not yet been reported, although their polymers are eventually absorbed, and only the metal platforms remain in the body. This study sought to determine the clinical safety and efficacy of BP-DESs with different platforms compared with other stents (other DESs and BMSs.PubMed, Embase and Clinical Trials.gov were searched for randomized controlled trials (RCTs that compared BP-DESs with other stents. After performing pooled analysis of BP-DESs and other stents, we performed a subgroup analysis using two classification methods: stent platform and follow-up time. The study characteristics, patient characteristics and clinical outcomes were abstracted.Forty RCTs (49 studies comprising 34,850 patients were included. Biodegradable polymer stainless drug-eluting stents (BP-stainless DESs were superior to the other stents [mainly stainless drug-eluting stents (DESs] in terms of pooled definite/probable stent thrombosis (ST (OR [95% CI] = 0.76[0.61-0.95], p = 0.02, long-term definite/probable ST (OR [95% CI] = 0.73[0.57-0.94], p = 0.01, very late definite/probable ST (OR [95% CI] = 0.56[0.33-0.93], p = 0.03 and long-term definite ST. BP-stainless DESs had lower rates of pooled, mid-term and long-term target vessel revascularization (TVR and target lesion revascularization (TLR than the other stainless DESs and BMSs. Furthermore, BP-stainless DESs were associated with lower rates of long-term death than other stainless DESs and lower rates of mid-term myocardial infarction than BMSs. However, only the mid-term and long-term TVR rates were superior in BP-alloy DESs compared with the other stents.Our results indirectly suggest that BP-stainless DESs may offer more

  19. Role of wild birds as carriers of multi-drug resistant Escherichia coli and Escherichia vulneris

    Science.gov (United States)

    Shobrak, Mohammed Y.; Abo-Amer, Aly E.

    2014-01-01

    Emergence and distribution of multi-drug resistant (MDR) bacteria in environments pose a risk to human and animal health. A total of 82 isolates of Escherichia spp. were recovered from cloacal swabs of migrating and non-migrating wild birds. All bacterial isolates were identified and characterized morphologically and biochemically. 72% and 50% of isolates recovered from non-migrating and migrating birds, respectively, showed positive congo red dye binding (a virulence factor). Also, hemolysin production (a virulence factor) was showed in 8% of isolates recovered from non-migrating birds and 75% of isolates recovered from migrating birds. All isolates recovered from non-migrating birds were found resistant to Oxacillin while all isolates recovered from migrating birds demonstrated resistance to Oxacillin, Chloramphenicol, Oxytetracycline and Lincomycin. Some bacterial isolates recovered from non-migrating birds and migrating birds exhibited MDR phenotype. The MDR isolates were further characterized by API 20E and 16S rRNA as E. coli and E. vulneris. MDR Escherichia isolates contain ~1–5 plasmids of high-molecular weights. Accordingly, wild birds could create a potential threat to human and animal health by transmitting MDR bacteria to water streams and other environmental sources through their faecal residues, and to remote regions by migration. PMID:25763023

  20. trans-Double Bond-Containing Liposomes as Potential Carriers for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Giorgia Giacometti

    2017-11-01

    Full Text Available The use of liposomes has been crucial for investigations in biomimetic chemical biology as a membrane model and in medicinal chemistry for drug delivery. Liposomes are made of phospholipids whose biophysical characteristics strongly depend on the type of fatty acid moiety, where natural unsaturated lipids always have the double bond geometry in the cis configuration. The influence of lipid double bond configuration had not been considered so far with respect to the competence of liposomes in delivery. We were interested in evaluating possible changes in the molecular properties induced by the conversion of the double bond from cis to trans geometry. Here we report on the effects of the addition of trans-phospholipids supplied in different amounts to other liposome constituents (cholesterol, neutral phospholipids and cationic surfactants, on the size, ζ-potential and stability of liposomal formulations and on their ability to encapsulate two dyes such as rhodamine B and fluorescein. From a biotechnological point of view, trans-containing liposomes proved to have different characteristics from those containing the cis analogues, and to influence the incorporation and release of the dyes. These results open new perspectives in the use of the unnatural lipid geometry, for the purpose of changing liposome behavior and/or of obtaining molecular interferences, also in view of synergic effects of cell toxicity, especially in antitumoral strategies.

  1. Biodegradable polyesters for veterinary drug delivery systems: Characterization, in vitro degradation and release behavior of Oligolactides and Polytartrate

    OpenAIRE

    Schliecker, Gesine

    2004-01-01

    This thesis deals with the degradation and release behavior of aliphatic polyesters with special respect to the influence of oligomers on the degradation rate and the potential use of these biomaterials for the development of veterinary drug delivery systems. In Chapter 1 the animal health care market is introduced with regard to opportunities and challenges of veterinary drug delivery systems. . In the second part of this chapter...

  2. Carrier-Mediated Prodrug Uptake to Improve the Oral Bioavailability of Polar Drugs: An Application to an Oseltamivir Analogue.

    Science.gov (United States)

    Incecayir, Tuba; Sun, Jing; Tsume, Yasuhiro; Xu, Hao; Gose, Tomoka; Nakanishi, Takeo; Tamai, Ikumi; Hilfinger, John; Lipka, Elke; Amidon, Gordon L

    2016-02-01

    The goal of this study was to improve the intestinal mucosal cell membrane permeability of the poorly absorbed guanidino analogue of a neuraminidase inhibitor, oseltamivir carboxylate (GOC) using a carrier-mediated strategy. Valyl amino acid prodrug of GOC with isopropyl-methylene-dioxy linker (GOC-ISP-Val) was evaluated as the potential substrate for intestinal oligopeptide transporter, hPEPT1 in Xenopus laevis oocytes heterologously expressing hPEPT1, and an intestinal mouse perfusion system. The diastereomers of GOC-ISP-Val were assessed for chemical and metabolic stability. Permeability of GOC-ISP-Val was determined in Caco-2 cells and mice. Diastereomer 2 was about 2 times more stable than diastereomer 1 in simulated intestinal fluid and rapidly hydrolyzed to the parent drug in cell homogenates. The prodrug had a 9 times-enhanced apparent permeability (P(app)) in Caco-2 cells compared with the parent drug. Both diastereomer exhibited high effective permeability (P(eff)) in mice, 6.32 ± 3.12 and 5.20 ± 2.81 × 10(-5) cm/s for diastereomer 1 and 2, respectively. GOC-ISP-Val was found to be a substrate of hPEPT1. Overall, this study indicates that the prodrug, GOC-ISP-Val, seems to be a promising oral anti-influenza agent that has sufficient stability at physiologically relevant pHs before absorption, significantly improved permeability via hPEPT1 and potentially rapid activation in the intestinal cells. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  3. Formulation and Characterization of Biodegradable Medicated ...

    African Journals Online (AJOL)

    (TPA), biodegradation, in vitro drug release using a modified chewing apparatus, and sensory properties. Result: Formulations code MCG-5 and MCG-9 which incorporated glyceryl triacetate and castor oil as plasticizers, respectively, showed a biodegradation score of 2 and 1, respectively, indicating significant.

  4. Bovine Serum Albumin (BSA) coated iron oxide magnetic nanoparticles as biocompatible carriers for curcumin-anticancer drug.

    Science.gov (United States)

    Nosrati, Hamed; Sefidi, Naser; Sharafi, Ali; Danafar, Hossein; Kheiri Manjili, Hamidreza

    2018-02-01

    The bovine serum albumin-coated magnetic nanoparticles (F@BSA NPs) were prepared as curcumin (CUR) carriers through desolvation and chemical co-precipitation process. The characteristics of CUR loaded F@BSA NPs (F@BSA@CUR NPs) were determined by X-ray diffraction (XRD), thermogravimetric analysis (TGA), fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and vibrating-sampling magnetometry (VSM) techniques. It was found that the synthesized F@BSA@CUR NPs were spherical in shape with an average size of 56 ± 11.43 nm (mean ± SD (n = 33)), ζ-potential of -10.1 mV, and good magnetic responsivity. Meanwhile, the drug content of the nanoparticles was 6.88%. These F@BSA@CUR NPs also demonstrated sustained release of CUR at 37 °C in different buffer solutions. Cellular toxicity of F@BSA@CUR NPs was studied on HFF2 cell line. Also, the cytotoxicity of F@BSA@CUR NPs towards MCF-7 breast cancer cells was investigated. The results revealed that F@BSA@CUR NPs have significant cytotoxicity activity on MCF-7 cell line. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Lipid nanocarriers (LNC) and their applications in ocular drug delivery.

    Science.gov (United States)

    Puglia, Carmelo; Offerta, Alessia; Carbone, Claudia; Bonina, Francesco; Pignatello, Rosario; Puglisi, Giovanni

    2015-01-01

    The peculiar physio-anatomical structure of the eye and the poor physico-chemical properties of many drug molecules are often responsible for the inefficient treatment of ocular diseases by conventional dosage forms, and justify the development of innovative ocular drug delivery systems. Lipid-based nanocarriers (LNC) are among the newer and interesting colloidal drug delivery systems; they show the capability to improve the local bioavailability of drugs administered by various ocular routes and, therefore, their therapeutic efficacy. Furthermore, their extreme biodegradability and biocompatible chemical nature have secured them the title of 'nanosafe carriers.' This review treats the main features of LNC [namely, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and lipid-drug conjugates (LDC)]; examples and advantages of the application of these colloidal carrier systems for the ophthalmic administration of drugs are presented.

  6. A biodegradable, sustained-released, prednisolone acetate microfilm drug delivery system effectively prolongs corneal allograft survival in the rat keratoplasty model.

    Directory of Open Access Journals (Sweden)

    Yu-Chi Liu

    Full Text Available Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA-loaded poly (d,l-lactide-co-ε-caprolactone (PLC microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK using a rat model. The drug release profiles of the microfilms were characterized (group 1. Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2, allogeneic control grafts (group 3, allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4, and allogeneic grafts with PA eye drops (group 5; n = 12 in each. PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006-0.009 mg/day, with a consistent aqueous drug concentration of 207-209 ng/ml. The mean survival days was >28 days in group 2, 9.9±0.8 days in group 3, 26.8±2.7 days in group 4, and 26.4±3.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3. Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P<0.001. There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loaded microfilm effectively prolongs corneal allograft survival. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation.

  7. 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.

  8. In vivo Pharmacological Evaluations of Pilocarpine-Loaded Antioxidant-Functionalized Biodegradable Thermogels in Glaucomatous Rabbits

    Science.gov (United States)

    Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang

    2017-02-01

    To alleviate oxidative stress-induced ocular hypertension, grafting of antioxidant molecules to drug carriers enables a dual-function mechanism to effectively treat glaucomatous intraocular pressure (IOP) dysregulation. Providing potential application for intracameral administration of antiglaucoma medications, this study, for the first time, aims to examine in vivo pharmacological efficacy of pilocarpine-loaded antioxidant-functionalized biodegradable thermogels in glaucomatous rabbits. A series of gallic acid (GA)-grafted gelatin-g-poly(N-isopropylacrylamide) (GN) polymers were synthesized via redox reactions at 20-50 °C. Our results showed that raising redox radical initiation reaction temperature maximizes GA grafting level, antioxidant activity, and water content at 40 °C. Meanwhile, increase in overall hydrophilicity of GNGA carriers leads to fast polymer degradation and early pilocarpine depletion in vivo, which is disadvantageous to offer necessary pharmacological performance at prolonged time. By contrast, sustained therapeutic drug concentrations in aqueous humor can be achieved for long-term (i.e., 28 days) protection against corneal aberration and retinal injury after pilocarpine delivery using dual-function optimized carriers synthesized at 30 °C. The GA-functionalized injectable hydrogels are also found to contribute significantly to enhancement of retinal antioxidant defense system and preservation of histological structure and electrophysiological function, thereby supporting the benefits of drug-containing antioxidant biodegradable thermogels to prevent glaucoma development.

  9. Anaerobic biodegradability of macropollutants

    DEFF Research Database (Denmark)

    Angelidaki, Irini

    2002-01-01

    A variety of test procedures for determination of anaerobic biodegradability has been reported. This paper reviews the methods developed for determination of anaerobic biodegradability of macro-pollutants. Anaerobic biodegradability of micro-pollutants is not included. Furthermore, factors...

  10. Development, optimization and evaluation of surfactant-based pulmonary nanolipid carrier system of paclitaxel for the management of drug resistance lung cancer using Box-Behnken design.

    Science.gov (United States)

    Kaur, Prabhjot; Garg, Tarun; Rath, Goutam; Murthy, R S Rayasa; Goyal, Amit K

    2016-07-01

    In the present study, nanostructured lipid carriers (NLCs) along with various surfactants loaded with paclitaxel (PTX) were prepared by an emulsification technique using a Box-Behnken design. The Box-Behnken design indicated that the most effective factors on the size and PDI were at high surfactant concentration (1.5%), low lipids ratio (6:4) and medium homogenization speed (6000 rpm). Among all the formulations, Tween 20-loaded NLCs show least particle size compared to Tween 80 and Tween 60. Entrapment efficiency of Tween 20, Tween 80 and Tween 60-loaded formulations were 82.40, 85.60 and 79.78%, respectively. Drug release of Tween 80, Tween 20 and Tween 60-loaded NLCs is 64.9, 62.3 and 59.7%, respectively (within 72 h). Maximum cellular uptake was observed with Tween 20 formulation on Caco-2 cell lines. Furthermore, spray drying of resultant NLCs was showed good flow properties and was selected for drug delivery to deeper airways. In-vivo studies demonstrated the better localization of drug within the lungs using different surfactant-based pulmonary delivery systems. From this study, we have concluded that delivering drugs through pulmonary route is advantageous for local action in lungs as maximum amount of drug concentration was observed in lungs. The surfactants could prove to be beneficial in treating drug resistance lung cancer by inhibiting P-gp efflux in the form of nano lipidic carriers.

  11. Acute toxicity evaluation of in situ gel-forming controlled drug delivery system based on biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) copolymer

    Energy Technology Data Exchange (ETDEWEB)

    Fang Fang; Gong Changyang; Dong Pengwei; Fu Shaozhi; Gu Yingchun; Guo Gang; Zhao Xia; Wei Yuquan; Qian Zhiyong, E-mail: anderson-qian@163.co, E-mail: zhiyongqian@scu.edu.c [State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041 (China)

    2009-04-15

    In this paper, biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) triblock copolymer was synthesized, and was characterized by FTIR, {sup 1}H-NMR and GPC. The PCL-PEG-PCL/dimethyl sulfoxide (DMSO) solution displayed in situ gelling behavior when subcutaneously injected into the body. Toxicity tests and a histopathological study were performed in BALB/c mice. We focused mainly on acute organ toxicity of BALB/c mice by subcutaneous injection. In the acute toxicity test, the dose of subcutaneous injection was 5 g/kg body weight (b.w.), and the mice were observed continuously for 14 days. For the histopathological study, samples including heart, lung, liver, kidneys, spleen, stomach and intestine were histochemically prepared and stained with hematoxylin-eosin for histopathological examination. No mortality or significant signs of toxicity were observed during the whole observation period, and there is no significant lesion to be shown in histopathological study of major organs in the mice. Therefore, the maximal tolerance dose of dimethyl sulfoxide (DMSO) solution of PCL-PEG-PCL copolymer by subcutaneous injection was calculated to be higher than 5 g/kg b.w. Therefore, the PCL-PEG-PCL/DMSO system was thought to be non-toxic after subcutaneous injection, and it might be a candidate for an in situ gelling controlled drug delivery system.

  12. Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog Model

    Directory of Open Access Journals (Sweden)

    Janne Koskimäki

    2015-01-01

    Full Text Available Nimodipine is a widely used medication for treating delayed cerebral ischemia (DCI after subarachnoid hemorrhage. When administrated orally or intravenously, systemic hypotension is an undesirable side effect. Intracranial subarachnoid delivery of nimodipine during aneurysm clipping may be more efficient way of preventing vasospasm and DCI due to higher concentration of nimodipine in cerebrospinal fluid (CSF. The risk of systemic hypotension may also be decreased with intracranial delivery. We used animal models to evaluate the feasibility of surgically implanting a silica-based nimodipine releasing implant into the subarachnoid space through a frontotemporal craniotomy. Concentrations of released nimodipine were measured from plasma samples and CSF samples. Implant degradation was followed using CT imaging. After completing the recovery period, full histological examination was performed on the brain and meninges. The in vitro characteristics of the implant were determined. Our results show that the biodegradable silica-based implant can be used for an intracranial drug delivery system and no major histopathological foreign body reactions were observed. CT imaging is a feasible method for determining the degradation of silica implants in vivo. The sustained release profiles of nimodipine in CSF were achieved. Compared to a traditional treatment, higher nimodipine CSF/plasma ratios can be obtained with the implant.

  13. Comparison of Vascular Responses Following New-Generation Biodegradable and Durable Polymer-Based Drug-Eluting Stent Implantation in an Atherosclerotic Rabbit Iliac Artery Model.

    Science.gov (United States)

    Nakazawa, Gaku; Torii, Sho; Ijichi, Takeshi; Nagamatsu, Hirofumi; Ohno, Yohei; Kurata, Fumi; Yoshikawa, Ayako; Nakano, Masataka; Shinozaki, Norihiko; Yoshimachi, Fuminobu; Ikari, Yuji

    2016-10-19

    Incomplete endothelialization is the primary substrate of late stent thrombosis; however, recent reports have revealed that abnormal vascular responses are also responsible for the occurrence of late stent failure. The aim of the current study was to assess vascular response following deployment of biodegradable polymer-based Synergy (Boston Scientific) and Nobori (Terumo) drug-eluting stents and the durable polymer-based Resolute Integrity stent (Medtronic) in an atherosclerotic rabbit iliac artery model. A total of 24 rabbits were fed an atherogenic diet, and then a balloon injury was used to induce atheroma formation. Synergy, Nobori, and Resolute Integrity stents were randomly implanted in iliac arteries. Animals were euthanized at 28 days for scanning electron microscopic evaluation and at 90 days for histological analysis. The percentage of uncovered strut area at 28 days was lowest with Synergy, followed by Resolute Integrity, and was significantly higher with Nobori stents (Synergy 1.1±2.2%, Resolute Integrity 2.0±3.9%, Nobori 4.6±3.0%; Pfastest stent strut neointimal coverage and the lowest incidence of neoatherosclerosis in the current animal model. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  14. Influence of Carrier (Polymer Type and Drug-Carrier Ratio in the Development of Amorphous Dispersions for Solubility and Permeability Enhancement of Ritonavir

    Directory of Open Access Journals (Sweden)

    Vivek S. Dave

    2017-09-01

    Full Text Available The influence of the ratio of Eudragit® L100-55 or Kolliphor® P188 on the solubility, dissolution, and permeability of ritonavir was studied with a goal of preparing solid dispersions (SDs of ritonavir. SDs were formulated using solvent evaporation or lyophilization techniques, and evaluated for their physical-chemical properties. The dissolution and permeability assessments of the functionality of the SDs were carried out. The preliminary functional stability of these formulations was assessed at accelerated storage conditions for a period of six months. Ritonavir: Eudragit® L100-55 (RE, 1:3 SD showed a 36-fold higher ritonavir solubility compared to pure ritonavir. Similarly, ritonavir: Kolliphor® P188 (RP, 1:2 SD exhibited a 49-fold higher ritonavir solubility compared to pure ritonavir. Ritonavir dissolution from RE formulations increased with increasing ratios of Eudragit® L100-55, up to a ritonavir: carrier ratio of 1:3. The ritonavir dissolution from RP formulations was highest at ritonavir: Kolliphor® P188 ratio of 1:2. Dissolution efficiencies of these formulations were found to be in line with, and supported the dissolution results. The permeability of ritonavir across the biological membrane from the optimized formulations RE (1:3 and RP (1:2 were ~76 % and ~97 %, respectively; and were significantly higher compared to that of pure ritonavir (~20 %. A preliminary (six-month stability study demonstrated the functional stability of prepared solid dispersions. The present study demonstrates that ritonavir solubility, dissolution, and permeability improvement can be achieved with a careful choice of the carrier polymer, and optimizing the amount of polymer in a SD formulation.

  15. Biodegradation and bioremediation

    DEFF Research Database (Denmark)

    Albrechtsen, H.-J.

    1996-01-01

    Anmeldelse af Alexander,M.: Biodegradation and bioremediation. Academic Press, Sandiego, USA, 1994......Anmeldelse af Alexander,M.: Biodegradation and bioremediation. Academic Press, Sandiego, USA, 1994...

  16. Formulation and Characterization of Biodegradable Medicated ...

    African Journals Online (AJOL)

    PEG)-600, tributyl citrate, PEG-200, PEG-300, PEG-400, PEG-4000, triethyl citrate and castor oil. The gum formulations were characterized for the following parameters: texture profile analysis (TPA), biodegradation, in vitro drug release using a ...

  17. A propensity score-matched comparison of biodegradable polymer vs second-generation durable polymer drug-eluting stents in a real-world population.

    Science.gov (United States)

    Zhao, Ying Jiao; Teng, Monica; Khoo, Ai Leng; Ananthakrishna, Rajiv; Yeo, Tiong Cheng; Lim, Boon Peng; Loh, Joshua P; Chan, Mark Y

    2018-04-01

    The safety and efficacy of BP-DES compared to second-generation DP-DES remain unclear in the real-world setting. We compared the clinical outcomes of biodegradable polymer drug-eluting stents (BP-DES) with second-generation durable polymer drug-eluting stents (DP-DES) in an all-comer percutaneous coronary intervention (PCI) registry. The study included a cohort of 1065 patients treated with either BP-DES or DP-DES from January 2009 through October 2015. Propensity score matching was performed to account for potential confounders and produced 497 matched pairs of patients. The primary endpoint was target lesion failure (TLF) at one-year follow-up. The rates of TLF were comparable between BP-DES and DP-DES (8.7% vs 9.1%, P = .823) at 1 year. The rates of stent thrombosis at 30 days (0.4% vs 0.4%, P = 1.00) and 1 year (0.8% vs 0.8%, P = 1.00) did not differ between BP-DES and DP-DES. There were no significant differences in other clinical outcomes including target vessel failure (8.9% vs 9.5%, P = .741), in-stent restenosis (1.8% vs 1.0%, P = .282), and cardiac death (6.4% vs 7.4%, P = .533) at 1 year. Multivariate cox regression analysis showed that the risk of TLF at one-year did not differ significantly between BP-DES and DP-DES (hazard ratio 0.94, P = .763). Efficacy and safety of BP-DES were not better than DP-DES at one-year follow-up. © 2018 John Wiley & Sons Ltd.

  18. Biodegradable polymeric prodrugs of naltrexone

    NARCIS (Netherlands)

    Bennet, D.B.; Li, X.; Adams, N.W.; Kim, S.W.; Hoes, C.J.T.; Hoes, C.J.T.; Feijen, Jan

    1991-01-01

    The development of a biodegradable polymeric drug delivery system for the narcotic antagonist naltrexone may improve patient compliance in the treatment of opiate addiction. Random copolymers consisting of the ¿-amino acids N5-(3-hydroxypropyl--glutamine and -leucine were synthesized with equimolar

  19. Lipid-based formulations solidified via adsorption onto the mesoporous carrier Neusilin® US2: effect of drug type and formulation composition on in vitro pharmaceutical performance.

    Science.gov (United States)

    Williams, Hywel D; Van Speybroeck, Michiel; Augustijns, Patrick; Porter, Christopher J H

    2014-06-01

    The current study determined the extent to which the desorption of lipid-based formulations (LBFs) from a mesoporous magnesium aluminometasilicate (Neusilin®-US2) carrier is governed by drug properties, LBF composition, and LBF-to-adsorbent ratio. A secondary objective was to evaluate the impact of testing parameters (medium composition, pH, dilution, and agitation) on in vitro LBF performance. Two self-emulsifying LBFs, with high/low lipid-surfactant ratios were studied in detail using danazol, fenofibrate, cinnarizine, and mefenamic acid as model drugs. A wider range of 38 different danazol-containing LBF were also evaluated, where desorption was evaluated immediately after preparation and after 1 month of storage. The results revealed that incomplete desorption from Neusilin® was a feature of all drugs and LBFs tested. Desorption was insensitive to agitation but increased under conditions where ionizable drugs were charged. In addition, formulations containing a higher proportion (>30%) of hydrophilic surfactant consistently exhibited higher desorption, and were least susceptible to decreased desorption on storage. In summary, although Neusilin® is an effective vehicle for LBF solidification, its use is accompanied by a risk of incomplete desorption of the vehicle from the carrier, irrespective of the drug. Lipid Formulation Classification System (LFCS)Type IIIB LBFs comprising higher quantities of hydrophilic surfactants appear to desorb most from Neusilin®. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. Mechanism and kinetics of the loss of poorly soluble drugs from liposomal carriers studied by a novel flow field-flow fractionation-based drug release-/transfer-assay.

    Science.gov (United States)

    Hinna, Askell Hvid; Hupfeld, Stefan; Kuntsche, Judith; Bauer-Brandl, Annette; Brandl, Martin

    2016-06-28

    Liposomes represent a versatile drug formulation approach e.g. for improving the water-solubility of poorly soluble drugs but also to achieve drug targeting and controlled release. For the latter applications it is essential that the drug remains associated with the liposomal carrier during transit in the vascular bed. A range of in vitro test methods has been suggested over the years for prediction of the release of drug from liposomal carriers. The majority of these fail to give a realistic prediction for poorly water-soluble drugs due to the intrinsic tendency of such compounds to remain associated with liposome bilayers even upon extensive dilution. Upon i.v. injection, in contrast, rapid drug loss often occurs due to drug transfer from the liposomal carriers to endogenous lipophilic sinks such as lipoproteins, plasma proteins or membranes of red blood cells and endothelial cells. Here we report on the application of a recently introduced in vitro predictive drug transfer assay based on incubation of the liposomal drug carrier with large multilamellar liposomes, the latter serving as a biomimetic model sink, using flow field-flow fractionation as a tool to separate the two types of liposomes. By quantifying the amount of drug remaining associated with the liposomal drug carrier as well as that transferred to the acceptor liposomes at distinct times of incubation, both the kinetics of drug transfer and release to the water phase could be established for the model drug p-THPP (5,10,15,20-tetrakis(4-hydroxyphenyl)21H,23H-porphine). p-THPP is structurally similar to temoporfin, a photosensitizer which is under clinical evaluation in a liposomal formulation. Mechanistic insights were gained by varying the donor-to-acceptor lipid mass ratio, size and lamellarity of the liposomes. Drug transfer kinetics from one liposome to another was found rate determining as compared to redistribution from the outermost to the inner concentric bilayers, such that the overall

  1. Impact of carriers in oral absorption

    DEFF Research Database (Denmark)

    Gram, Luise Kvisgaard; Rist, Gerda Marie; Lennernäs, Hans

    2009-01-01

    Carriers may mediate the permeation across enterocytes for drug substances being organic anions. Carrier mediated permeation for the organic anions estrone-3-sulfate (ES) and glipizide across Caco-2 cells were investigated kinetically, and interactions on involved carriers evaluated. Initial...

  2. Magnetic polymer nanospheres for anticancer drug targeting

    International Nuclear Information System (INIS)

    JurIkova, A; Csach, K; Koneracka, M; Zavisova, V; Tomasovicova, N; Lancz, G; Kopcansky, P; Timko, M; Miskuf, J; Muckova, M

    2010-01-01

    Poly(D,L-lactide-co-glycolide) polymer (PLGA) nanospheres loaded with biocom-patible magnetic fluid as a magnetic carrier and anticancer drug Taxol were prepared by the modified nanoprecipitation method with size of 200-250 nm in diameter. The PLGA polymer was utilized as a capsulation material due to its biodegradability and biocompatibility. Taxol as an important anticancer drug was chosen for its significant role against a wide range of tumours. Thermal properties of the drug-polymer system were characterized using thermal analysis methods. It was determined the solubility of Taxol in PLGA nanospheres. Magnetic properties investigated using SQUID magnetometry showed superparamagnetism of the prepared magnetic polymer nanospheres.

  3. Biodegradable Piezoelectric Force Sensor.

    Science.gov (United States)

    Curry, Eli J; Ke, Kai; Chorsi, Meysam T; Wrobel, Kinga S; Miller, Albert N; Patel, Avi; Kim, Insoo; Feng, Jianlin; Yue, Lixia; Wu, Qian; Kuo, Chia-Ling; Lo, Kevin W-H; Laurencin, Cato T; Ilies, Horea; Purohit, Prashant K; Nguyen, Thanh D

    2018-01-30

    Measuring vital physiological pressures is important for monitoring health status, preventing the buildup of dangerous internal forces in impaired organs, and enabling novel approaches of using mechanical stimulation for tissue regeneration. Pressure sensors are often required to be implanted and directly integrated with native soft biological systems. Therefore, the devices should be flexible and at the same time biodegradable to avoid invasive removal surgery that can damage directly interfaced tissues. Despite recent achievements in degradable electronic devices, there is still a tremendous need to develop a force sensor which only relies on safe medical materials and requires no complex fabrication process to provide accurate information on important biophysiological forces. Here, we present a strategy for material processing, electromechanical analysis, device fabrication, and assessment of a piezoelectric Poly-l-lactide (PLLA) polymer to create a biodegradable, biocompatible piezoelectric force sensor, which only employs medical materials used commonly in Food and Drug Administration-approved implants, for the monitoring of biological forces. We show the sensor can precisely measure pressures in a wide range of 0-18 kPa and sustain a reliable performance for a period of 4 d in an aqueous environment. We also demonstrate this PLLA piezoelectric sensor can be implanted inside the abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction. This piezoelectric sensor offers an appealing alternative to present biodegradable electronic devices for the monitoring of intraorgan pressures. The sensor can be integrated with tissues and organs, forming self-sensing bionic systems to enable many exciting applications in regenerative medicine, drug delivery, and medical devices.

  4. Drug-eluting stents with biodegradable polymer for the treatment of patients with diabetes mellitus: clinical outcome at 2 years in a large population of patients

    Directory of Open Access Journals (Sweden)

    Wiemer M

    2015-02-01

    Full Text Available Marcus Wiemer,1 Gian Battista Danzi,2 Nick West,3 Vassilios Voudris,4 René Koning,5 Stefan Hoffmann,6 Mario Lombardi,7 Josepa Mauri,8 Rade Babic,9 Fraser Witherow10On behalf of the NOBORI 2 Investigators 1Department of Cardiology, Heart and Diabetes Center North Rhine–Westphalia, Ruhr University Bochum, Bad Oeynhausen, Germany; 2Ospedale Maggiore Policlinico, Milan, Italy; 3Papworth Hospital, Cambridge, UK; 4Onassis Cardiac Surgery Center, Athens, Greece; 5Clinique Saint Hilaire, Rouen, France; 6Vivantes Netzwerk für Gesundheit GmbH, Berlin, Germany; 7Azienda Ospedaliera Villa Sofia, Palermo, Italy; 8Hospital Universitari Germans Trias i Pujol, Badalona, Spain; 9Institute for Cardiovascular Diseases Dedinje, Belgrade, Serbia; 10Dorset County Hospital, Dorchester, UK Objective: This study investigates the safety and efficacy of a third-generation drug-eluting stent (DES with biodegradable polymer in the complex patient population of diabetes mellitus (DM. Clinical trial registration: ISRCTN81649913. Background: Percutaneous coronary interventions in patients with DM are associated with a higher incidence of death, restenosis, and stent thrombosis as compared to non-diabetic patients. The use of a DES has been shown to improve outcomes in diabetic patients. Methods: Out of 3,067 patients, enrolled in 126 centers worldwide in the NOBORI 2 registry, 888 patients suffered from DM, 213 of them (14% being insulin-dependent DM (IDDM. Two years’ follow-up has been completed in this study. Results: At 1- and 2-year follow-up, 97% and 95% of the patients, respectively, were available. The reported target lesion failure (TLF rates at 1- and 2-year follow-up were 6.0% and 7.2% in the DM group, respectively, and 3.0% and 4.2% in the non-DM group, respectively (P<0.001 for both years. Inside the DM group, the TLF rates of 9.9% and 11.7% at the 1- and 2-year follow-ups, respectively, in patients with IDDM were significantly higher than the TLF rates of 4

  5. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers. I. Effect of formulation variables on the physicochemical properties, drug release and stability of clotrimazole-loaded nanoparticles.

    Science.gov (United States)

    Das, Surajit; Ng, Wai Kiong; Tan, Reginald B H

    2014-03-14

    The objective of this study was to develop and evaluate solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) utilizing sucrose ester as a stabilizer/emulsifier for the controlled release of drug/active. Both SLNs and NLCs were prepared using different sugar esters to screen out the most suitable stabilizer. Clotrimazole was used as a model active/drug. The effect of different formulation variables on the particle size, polydispersity index and drug encapsulation efficiency of SLNs and NLCs was evaluated and compared. SLNs and NLCs were physicochemically characterized and compared using Cryo-SEM, DSC and XRD. Furthermore, a drug release study of SLNs and NLCs was conducted. Finally, physicochemical stability (size, PI, ZP, EE) of the SLNs and NLCs was checked at 25 ± 2 °C and at 2-8 °C. Among the sucrose esters, D-1216 was found to be most suitable for both SLNs and NLCs. Formulation variables exhibited a significant impact on size, PI and EE of the nanoparticles. SLNs with ∼120 nm size, ∼0.23 PI, ∼I26I mV ZP, ∼87% EE and NLCs with ∼160 nm size, 0.15 PI, ∼I26I mV ZP, ∼88% EE were produced. Cryo-SEM revealed spherical particles with a smooth surface but did not exhibit any difference in surface morphology between SLNs and NLCs. DSC and XRD results demonstrated the disappearance of clotrimazole peak(s) in drug-loaded SLNs and NLCs. Faster drug release was observed from SLNs than NLCs. NLCs were found to be more stable than SLNs in terms of size, PI, EE and drug release. The results indicated that both SLNs and NLCs stabilized with sucrose ester D-1216 can be used as controlled release carriers although NLCs have an edge over SLNs.

  6. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers: I. Effect of formulation variables on the physicochemical properties, drug release and stability of clotrimazole-loaded nanoparticles

    Science.gov (United States)

    Das, Surajit; Kiong Ng, Wai; Tan, Reginald B. H.

    2014-03-01

    The objective of this study was to develop and evaluate solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) utilizing sucrose ester as a stabilizer/emulsifier for the controlled release of drug/active. Both SLNs and NLCs were prepared using different sugar esters to screen out the most suitable stabilizer. Clotrimazole was used as a model active/drug. The effect of different formulation variables on the particle size, polydispersity index and drug encapsulation efficiency of SLNs and NLCs was evaluated and compared. SLNs and NLCs were physicochemically characterized and compared using Cryo-SEM, DSC and XRD. Furthermore, a drug release study of SLNs and NLCs was conducted. Finally, physicochemical stability (size, PI, ZP, EE) of the SLNs and NLCs was checked at 25 ± 2 °C and at 2-8 °C. Among the sucrose esters, D-1216 was found to be most suitable for both SLNs and NLCs. Formulation variables exhibited a significant impact on size, PI and EE of the nanoparticles. SLNs with ˜120 nm size, ˜0.23 PI, ˜I26I mV ZP, ˜87% EE and NLCs with ˜160 nm size, 0.15 PI, ˜I26I mV ZP, ˜88% EE were produced. Cryo-SEM revealed spherical particles with a smooth surface but did not exhibit any difference in surface morphology between SLNs and NLCs. DSC and XRD results demonstrated the disappearance of clotrimazole peak(s) in drug-loaded SLNs and NLCs. Faster drug release was observed from SLNs than NLCs. NLCs were found to be more stable than SLNs in terms of size, PI, EE and drug release. The results indicated that both SLNs and NLCs stabilized with sucrose ester D-1216 can be used as controlled release carriers although NLCs have an edge over SLNs.

  7. Long-circulating poly(ethylene glycol)-coated poly(lactid-co-glycolid) microcapsules as potential carriers for intravenously administered drugs.

    Science.gov (United States)

    Ferenz, Katja B; Waack, Indra N; Mayer, Christian; de Groot, Herbert; Kirsch, Michael

    2013-01-01

    The intrinsic advantages of microcapsules with regard to nanocapsules as intravenous drug carrier systems are still not fully exploited. Especially, in clinical situations where a long-term drug release within the vascular system is desired, if large amounts of drug have to be administered or if capillary leakage occurs, long-circulating microparticles may display a superior alternative to nanoparticles. Here, microcapsules were synthesised and parameters such as in vitro tendency of agglomeration, protein adsorption and in vivo performance were investigated. Biocompatible poly(ethylene glycol) (PEG)-coated poly(DL-lactide-co-glycolide) (PLGA) as wall material, solid and perfluorodecalin (PFD)-filled PEG-PLGA microcapsules (1.5 µm diameter) were manufactured by using a modified solvent evaporation method with either 1% poly(vinyl alcohol) (PVA) or 1.5% cholate as emulsifying agents. Compared to microcapsules manufactured with cholate, the protein adsorption (albumin and IgG) was clearly decreased and agglomeration of capsules was prevented, when PVA was used. The intravenous administration of these microcapsules, both solid and PFD-filled, in rats was successful and exhibited a circulatory half-life of about 1 h. Our data clearly demonstrate that PEG-PLGA microcapsules, manufactured by using PVA, are suitable biocompatible, long-circulating drug carriers, applicable for intravenous administration.

  8. Impact of hydrogenation on physicochemical and biomedical properties of pH-sensitive PMAA-b-HTPB-b-PMAA triblock copolymer drug carriers.

    Science.gov (United States)

    Xu, Feng; Xu, Jing-Wen; Luo, Yan-Ling

    2016-05-01

    pH-Sensitive poly(methacrylic acid)-block-hydroxyl-terminated polybutadiene-block-poly(methacrylic acid) (PMAA-b-HTPB-b-PMAA) was synthesized and then hydrogenated in this work. The chain structure, phase behavior and thermal properties were characterized by(1)H NMR, FTIR, XRD, DSC, TGA, etc., and the physicochemical and biomedical properties were investigated via fluorescence spectroscopy, TEM, DLS, loading and release of drug and MTT, and so on. The experimental results indicated that the hydrogenation led to the change in the chain aggregate structure of hydrophobic HTPB blocks and the formation of more stable spherical core-shell micelle aggregates, and the critical micelle concentration decreased from 41.8 mg L(-1)before hydrogenation to 4.4 mg L(-1)after hydrogenation. The hydrogenated block copolymer micelle aggregates exhibited pH-triggered response, and could entrap twice as much hydrophobic drug as the unhydrided counterparts and the encapsulation efficiency was significantly improved, which makes them fine to meet the requirements for drug carriers. Therefore, the hydrogenated PMAA-b-HTPB-b-PMAA copolymer micelles as drug target release carriers can be well used in the field of prevention and treatment of cancers. © The Author(s) 2016.

  9. Utilization of bio-degradable fermented tapioca to synthesized low toxicity of carbon nanotubes for drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Nurulhuda, I., E-mail: nurulnye@gmail.com [NANO-SciTech Centre, Institute of Science, Universiti Teknologi MARA, 40450 Shah Alam, Selangor (Malaysia); Poh, R. [Department of Molecular Medicine, University of Malaya, 50603 Kuala Lumpur (Malaysia); Mazatulikhma, M. Z. [Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor (Malaysia); Rusop, M., E-mail: nanouitm@gmail.com [NANO-Electronic Centre, Faculty of Electrical Engineering, Universiti Teknologi MARA, 40450 Shah Alam, Selangor (Malaysia); Salman, A. H. A.; Haseeb, A. K.

    2016-07-06

    Carbon nanotubes (CNT) have potential biomedical applications, and investigations are shifting towards the production of such nanotubes using renewable natural sources. CNTs were synthesized at various temperatures of 700, 750, 800, 850 and 900 °C, respectively, using a local fermented food known as “tapai ubi” or fermented tapioca as a precursor. The liquid part of this fermented food was heated separately at 80°C and channeled directly into the furnace system that employs the thermal chemical vapor deposition (CVD) method. Ferrocene, which was the catalyst was placed in furnace 1 in the thermal CVD process. The resulting CNTs produced from the process were studied using field emission scanning electron microscopy (FESEM) and Raman spectroscopy. The FESEM images showed the growth morphology of the CNTs at the different temperatures employed. It was observed that the higher the synthesis temperature up to a point, the diameter of CNTs produced, after which the diameter increased. CNTs with helical structures were observed at 700 °C with a diameter range of 111 - 143 nm. A more straightened structure was observed at 750 °C with a diameter range of 59 - 121 nm. From 800 °C onwards, the diameters of the CNTs were less than 60 nm. Raman analysis revealed the present of D, G and G’ peak were observed at 1227-1358, 1565-1582, and 2678-2695 cm{sup −1}, respectively. The highest degree of crystallity of the carbon nanotubes synthesized were obtained at 800 °C. The radial breathing mode (RBM) were in range between 212-220 and 279-292 cm{sup −1}. Carbon nanotubes also being functionalized with Polyethylene bis(amine) Mw2000 (PEG 2000-NH2) and showed highly cells viability compared to non-functionalized CNT. The nanotubes synthesized will be applied as drug delivery in future study.

  10. Utilization of bio-degradable fermented tapioca to synthesized low toxicity of carbon nanotubes for drug delivery applications

    International Nuclear Information System (INIS)

    Nurulhuda, I.; Poh, R.; Mazatulikhma, M. Z.; Rusop, M.; Salman, A. H. A.; Haseeb, A. K.

    2016-01-01

    Carbon nanotubes (CNT) have potential biomedical applications, and investigations are shifting towards the production of such nanotubes using renewable natural sources. CNTs were synthesized at various temperatures of 700, 750, 800, 850 and 900 °C, respectively, using a local fermented food known as “tapai ubi” or fermented tapioca as a precursor. The liquid part of this fermented food was heated separately at 80°C and channeled directly into the furnace system that employs the thermal chemical vapor deposition (CVD) method. Ferrocene, which was the catalyst was placed in furnace 1 in the thermal CVD process. The resulting CNTs produced from the process were studied using field emission scanning electron microscopy (FESEM) and Raman spectroscopy. The FESEM images showed the growth morphology of the CNTs at the different temperatures employed. It was observed that the higher the synthesis temperature up to a point, the diameter of CNTs produced, after which the diameter increased. CNTs with helical structures were observed at 700 °C with a diameter range of 111 - 143 nm. A more straightened structure was observed at 750 °C with a diameter range of 59 - 121 nm. From 800 °C onwards, the diameters of the CNTs were less than 60 nm. Raman analysis revealed the present of D, G and G’ peak were observed at 1227-1358, 1565-1582, and 2678-2695 cm −1 , respectively. The highest degree of crystallity of the carbon nanotubes synthesized were obtained at 800 °C. The radial breathing mode (RBM) were in range between 212-220 and 279-292 cm −1 . Carbon nanotubes also being functionalized with Polyethylene bis(amine) Mw2000 (PEG 2000-NH2) and showed highly cells viability compared to non-functionalized CNT. The nanotubes synthesized will be applied as drug delivery in future study.

  11. Carrier Diagnosis

    Science.gov (United States)

    ... Inheritance of Hemophilia Definitions & Terminology Bleeding Symptoms Carrier Diagnosis When to Test for Carrier Status Family Planning and Pregnancy Conception Options Prenatal Diagnosis Fetal Sex ...

  12. Biodegradable polymers for electrospinning: towards biomedical applications.

    Science.gov (United States)

    Kai, Dan; Liow, Sing Shy; Loh, Xian Jun

    2014-12-01

    Electrospinning has received much attention recently due to the growing interest in nano-technologies and the unique material properties. This review focuses on recent progress in applying electrospinning technique in production of biodegradable nanofibers to the emerging field of biomedical. It first introduces the basic theory and parameters of nanofibers fabrication, with focus on factors affecting the morphology and fiber diameter of biodegradable nanofibers. Next, commonly electrospun biodegradable nanofibers are discussed, and the comparison of the degradation rate of nanoscale materials with macroscale materials are highlighted. The article also assesses the recent advancement of biodegradable nanofibers in different biomedical applications, including tissue engineering, drug delivery, biosensor and immunoassay. Future perspectives of biodegradable nanofibers are discussed in the last section, which emphasizes on the innovation and development in electrospinning of hydrogels nanofibers, pore size control and scale-up productions. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Potential of surface-eroding poly(ethylene carbonate) for drug delivery to macrophages

    DEFF Research Database (Denmark)

    Bohr, Adam; Water, Jorrit J; Wang, Yingya

    2016-01-01

    Films composed of poly(ethylene carbonate) (PEC), a biodegradable polymer, were compared with poly(lactide-co-glycolide) (PLGA) films loaded with and without the tuberculosis drug rifampicin to study the characteristics and performance of PEC as a potential carrier for controlled drug delivery...... surface erosion (by cholesterol esterase). Drug release studies performed with polymer films indicated a diffusion/erosion dependent delivery behavior for PLGA while an almost zero-order drug release profile was observed from PEC due to the controlled polymer degradation process. When exposed to polymer...... for controlled drug release and could provide superior performance to PLGA for some drug delivery applications including the treatment of macrophage infections....

  14. Screening of lipid carriers and characterization of drug-polymer-lipid interactions for the rational design of polymer-lipid hybrid nanoparticles (PLN).

    Science.gov (United States)

    Li, Yongqiang; Taulier, Nicolas; Rauth, Andrew M; Wu, Xiao Yu

    2006-08-01

    The thermodynamics and solid state properties of components and their interactions in a formulation for polymer-lipid hybrid nanoparticles (PLN) were characterized for screening lead lipid carriers and rational design of PLN. Verapamil HCI (VRP) was chosen as a model drug and dextran sulfate sodium (DS) as a counter-ionic polymer. Solubility parameters of VRP, VRP-DS complex, and various lipids were calculated and partition of VRP and VRP-DS in lipids was determined. Thermodynamics of VRP binding to DS was determined by isothermal titration calorimetry (ITC). The solid state properties of individual components and their interactions were characterized using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Dodecanoic acid (DA) was identified as the best lipid carrier among all lipids tested based on the solubility parameters and partition coefficients. VRP-DS complexation was a thermodynamically favorable process. Maximum binding capacity of DS and the highest drug loading capacity of DA were obtained at an equal ionic molar ratio of DS to VRP. In the PLN formulation, DA remained its crystal structure but had a slightly lower melting point, while VRP-DS complex was in an amorphous form. Drug loading efficiency and capacity of a lipid matrix depend on the VRP-DS binding and the interactions of the complex with the lipid. A combined analysis of solubility parameters and partition coefficients is useful for screening lipid candidates for PLN preparation.

  15. Nanoparticle carriers based on copolymers of poly(l-aspartic acid co-l-lactide)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine for drug delivery

    International Nuclear Information System (INIS)

    Han Siyuan; Wang Huan; Liang Xingjie; Hu Liming; Li Min; Wu Yan

    2011-01-01

    A novel poly(l-aspartic) derivative (PAL-DPPE) containing polylactide and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) segments has been successfully synthesized. The chemical structures of the copolymers were confirmed by Fourier-transform infrared spectroscopy (FTIR), NMR ( 1 H NMR, 13 C NMR, 31 P NMR), and thermogravimetric analysis (TGA). Fluorescence spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) confirmed the formation of micelles of the PAL-DPPE copolymers. In order to estimate the feasibility as novel drug carriers, an anti-tumor model drug doxorubicin (DOX) was incorporated into polymeric micelles by double emulsion and nanoprecipitation method. The DOX-loaded micelle size, size distribution, and encapsulation efficiency (EE) were influenced by the feed weight ratio of the copolymer to DOX. In addition, in vitro release experiments of the DOX-loaded PAL-DPPE micelles exhibited that faster release in pH 5.0 than their release in pH 7.4 buffer. The poly(l-aspartic) derivative copolymer was proved to be an available carrier for the preparation of micelles for anti-tumor drug delivery.

  16. Cholesterol-Modified Amino-Pullulan Nanoparticles as a Drug Carrier: Comparative Study of Cholesterol-Modified Carboxyethyl Pullulan and Pullulan Nanoparticles

    Directory of Open Access Journals (Sweden)

    Xiaojun Tao

    2016-09-01

    Full Text Available To search for nano-drug preparations with high efficiency in tumor treatment, we evaluated the drug-loading capacity and cell-uptake toxicity of three kinds of nanoparticles (NPs. Pullulan was grafted with ethylenediamine and hydrophobic groups to form hydrophobic cholesterol-modified amino-pullulan (CHAP conjugates. Fourier transform infrared spectroscopy and nuclear magnetic resonance were used to identify the CHAP structure and calculate the degree of substitution of the cholesterol group. We compared three types of NPs with close cholesterol hydrophobic properties: CHAP, cholesterol-modified pullulan (CHP, and cholesterol-modified carboxylethylpullulan (CHCP, with the degree of substitution of cholesterol of 2.92%, 3.11%, and 3.46%, respectively. As compared with the two other NPs, CHAP NPs were larger, 263.9 nm, and had a positive surface charge of 7.22 mV by dynamic light-scattering measurement. CHAP NPs showed low drug-loading capacity, 12.3%, and encapsulation efficiency of 70.8%, which depended on NP hydrophobicity and was affected by surface charge. The drug release amounts of all NPs increased in the acid media, with CHAP NPs showing drug-release sensitivity with acid change. Cytotoxicity of HeLa cells was highest with mitoxantrone-loaded CHAP NPs on MTT assay. CHAP NPs may have potential as a high-efficiency drug carrier for tumor treatment.

  17. Design of in situ dispersible and calcium cross-linked alginate pellets as intestinal-specific drug carrier by melt pelletization technique.

    Science.gov (United States)

    Nurulaini, Harjoh; Wong, Tin Wui

    2011-06-01

    Conventional alginate pellets underwent rapid drug dissolution and loss of multiparticulate characteristics such as aggregation in acidic medium, thereby promoting oral dose dumping. This study aimed to design sustained-release dispersible alginate pellets through rapid in situ matrix dispersion and cross-linking by calcium salts during dissolution. Pellets made of alginate and calcium salts were prepared using a solvent-free melt pelletization technique that prevented reaction between processing materials during agglomeration and allowed such a reaction to occur only in dissolution phase. Drug release was remarkably retarded in acidic medium when pellets were formulated with water-soluble calcium acetate instead of acid-soluble calcium carbonate. Different from calcium salt-free and calcium carbonate-loaded matrices that aggregated or underwent gradual erosion, rapid in situ solvation of calcium acetate in pellets during dissolution resulted in burst of gas bubbles, fast pellet breakup, and dispersion. The dispersed fragments, though exhibiting a larger specific surface area for drug dissolution than intact matrix, were rapidly cross-linked by Ca(2+) from calcium acetate and had drug release retarded till a change in medium pH from 1.2 to 6.8. Being dispersible and pH-dependent in drug dissolution, these pellets are useful as multiparticulate intestinal-specific drug carrier without exhibiting dose dumping tendency of a "single-unit-like" system via pellet aggregation. Copyright © 2011 Wiley-Liss, Inc.

  18. Feasibility study of silica sol as the carrier of a hydrophobic drug in aqueous solution using enrofloxacin as the model

    International Nuclear Information System (INIS)

    Song Meirong; Song Junling; Ning Aimin; Cui Baoan; Cui Shumin; Zhou Yaobing; An Wankai; Dong Xuesong; Zhang Gege

    2010-01-01

    The aim of this study was to determine the feasibility of using silica sol to carry a hydrophobic drug in aqueous solution. Enrofloxacin, which was selected as the model drug because it is a broad-spectrum antibiotic drug with poor solubility in water, was adsorbed onto silica sol in aqueous solution during cooling from 60 deg. C to room temperature. The drug-loaded silica sol was characterized by transmission electron microscopy, Fourier transform infrared spectrum, thermal gravimetric analysis and ultraviolet-visible light spectroscopy. The results showed that enrofloxacin was adsorbed by silica sol without degradation at a loading of 15.23 wt.%. In contrast to the rapid release from pure enrofloxacin, the drug-loaded silica sol showed a slower release over a longer time. Kinetics analysis suggested the drug release from silica sol was mainly a diffusion-controlled process. Therefore, silica sol can be used to carry a hydrophobic drug in aqueous solution for controlled drug delivery.

  19. Gallic acid grafting effect on delivery performance and antiglaucoma efficacy of antioxidant-functionalized intracameral pilocarpine carriers.

    Science.gov (United States)

    Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang

    2016-07-01

    Functionalization of therapeutic carrier biomaterials can potentially provide additional benefits in drug delivery for disease treatment. Given that this modification determines final therapeutic efficacy of drug carriers, here, we investigate systematically the role of grafting amount of antioxidant gallic acid (GA) onto GN in situ gelling copolymers made of biodegradable gelatin and thermo-responsive poly(N-isopropylacrylamide) for intracameral delivery of pilocarpine in antiglaucoma treatment. As expected, increasing redox reaction time increased total antioxidant activities and free radical scavenging abilities of synthesized carrier biomaterials. The hydrophilic nature of antioxidant molecules strongly affected physicochemical properties of carrier materials with varying GA grafting amounts, thereby dictating in vitro release behaviors and mechanisms of pilocarpine. In vitro oxidative stress challenges revealed that biocompatible carriers with high GA content alleviated lens epithelial cell damage and reduced reactive oxygen species. Intraocular pressure and pupil diameter in glaucomatous rabbits showed correlations with GA-mediated release of pilocarpine. Additionally, enhanced pharmacological treatment effects prevented corneal endothelial cell loss during disease progression. Increasing GA content increased total antioxidant level and decreased nitrite level in the aqueous humor, suggesting a much improved antioxidant status in glaucomatous eyes. This work significantly highlights the dependence of physicochemical properties, drug release behaviors, and bioactivities on intrinsic antioxidant capacities of therapeutic carrier biomaterials for glaucoma treatment. Development of injectable biodegradable polymer depots and functionalization of carrier biomaterials with antioxidant can potentially provide benefits such as improved bioavailability, controlled release pattern, and increased therapeutic effect in intracameral pilocarpine administration for glaucoma

  20. Magnetic and fluorescent carbon-based nanohybrids for multi-modal imaging and magnetic field/NIR light responsive drug carriers.

    Science.gov (United States)

    Wang, Hui; Zhou, Shuiqin

    2016-07-21

    Carbon nanomaterials have gained significant momentum as promising candidate materials for biomedical applications due to their unique structure and properties. After functionalization with magnetic and fluorescent components, the resultant carbon-based nanohybrids can serve not only as magnetic resonance and fluorescence imaging contrast agents, but also as photothermally/magneto-thermally responsive drug carriers for combined photothermo/chemotherapy. This mini-review summarizes the latest developments and applications and addresses the future perspectives of carbon-based magnetic and fluorescent nanohybrids in the biomedical field.

  1. Dual effect of F-actin targeted carrier combined with antimitotic drug on aggressive colorectal cancer cytoskeleton: Allying dissimilar cell cytoskeleton disrupting mechanisms.

    Science.gov (United States)

    Taranejoo, Shahrouz; Janmaleki, Mohsen; Pachenari, Mohammad; Seyedpour, Seyed Morteza; Chandrasekaran, Ramya; Cheng, Wenlong; Hourigan, Kerry

    2016-11-20

    A recent approach to colon cancer therapy is to employ selective drugs with specific extra/intracellular sites of action. Alteration of cytoskeletal protein reorganization and, subsequently, to cellular biomechanical behaviour during cancer progression highly affects the cancer cell progress. Hence, cytoskeleton targeted drugs are an important class of cancer therapy agents. We have studied viscoelastic alteration of the human colon adenocarcinoma cell line, SW48, after treatment with a drug delivery system comprising chitosan as the carrier and albendazole as the microtubule-targeting agent (MTA). For the first time, we have evaluated the biomechanical characteristics of the cell line, using the micropipette aspiration (MA) method after treatment with drug delivery systems. Surprisingly, employing a chitosan-albendazole pair, in comparison with both neat materials, resulted in more significant change in the viscoelastic parameters of cells, including the elastic constants (K 1 and K 2 ) and the coefficient of viscosity (μ). This difference was more pronounced for cancer cells after 48h of the treatment. Microtubule and actin microfilament (F-actin) contents in the cell line were studied by immunofluorescent staining. Good agreement was observed between the mechanical characteristics results and microtubule/F-actin contents of the treated SW48 cell line, which declined after treatment. The results showed that chitosan affected F-actin more, while MTA was more effective for microtubules. Toxicity studies were performed against two cancer cell lines (SW48 and MCF10CA1h) and compared to normal cells, MCF10A. The results showed cancer selectiveness, safety of formulation, and enhanced anticancer efficacy of the CS/ABZ conjugate. This study suggests that employing such a suitable pair of drug-carriers with dissimilar sites of action, thus allying the different cell cytoskeleton disrupting mechanisms, may provide a more efficient cancer therapy approach. Copyright

  2. Biodegradable versus durable polymer drug eluting stents in coronary artery disease: insights from a meta-analysis of 5,834 patients.

    Science.gov (United States)

    Lupi, Alessandro; Rognoni, Andrea; Secco, Gioel Gabrio; Lazzero, Maurizio; Nardi, Federico; Fattori, Rossella; Bongo, Angelo Sante; Agostoni, Pierfrancesco; Sheiban, Imad

    2014-04-01

    Biodegradable polymer drug eluting stents (BP-DES) have been developed to overcome the limitations of first generation durable polymer DES (DP-DES) but the clinical results of different BP-DES are not consistent. We performed a meta-analysis to compare the outcomes of BP-DES and DP-DES in the treatment of coronary artery disease (CAD). Online databases including MEDLINE were searched for studies comparing BP-DES and DP-DES for obstructive CAD that reported rates for overall mortality, myocardial infarction (MI), late stent thrombosis (LST), target lesion revascularization (TLR) and late lumen loss (LLL) with a follow-up of ≥ 6 months. Ten studies (5834 patients) with a 1-year median follow-up were included in the meta-analysis. When comparing patients treated with DP-DES and BP-DES those treated with BP-DES had lower LLL (in-stent: weighted mean difference (WMD) -0.10 mm, 95% CI = -0.17 to -0.03 mm, p = 0.004; in-segment: WMD -0.06 mm, 95% CI = -0.10 to -0.01 mm, p = 0.01) with lower TLR rates (OR 0.67, 95% CI = 0.47 to 0.98, p = 0.04). However, BP-DES did not improve mortality (OR 0.97, 95% CI = 0.73 to 1.29, p = 0.83), MI (OR 1.13, 95% CI = 0.87 to 1.46, p = 0.36) or LST rates (OR 0.64, 95% CI = 0.36 to 1.16, p = 0.14). A pre-specified subgroup analysis of Biolimus BP-DES confirmed significant LLL reduction without differences in other clinical endpoints. Meta-regression analysis demonstrated a strong significant inverse correlation between LLL and reference coronary diameter (p meta-analysis showed that BP-DES when compared with DP-DES significantly reduced LLL and TVR but without clear benefits on mortality, MI and LST rates. (Clinicaltrials.gov identifier: NCT01466634).

  3. Polylactic acid (PLA) controlled delivery carriers for biomedical applications.

    Science.gov (United States)

    Tyler, Betty; Gullotti, David; Mangraviti, Antonella; Utsuki, Tadanobu; Brem, Henry

    2016-12-15

    Polylactic acid (PLA) and its copolymers have a long history of safety in humans and an extensive range of applications. PLA is biocompatible, biodegradable by hydrolysis and enzymatic activity, has a large range of mechanical and physical properties that can be engineered appropriately to suit multiple applications, and has low immunogenicity. Formulations containing PLA have also been Food and Drug Administration (FDA)-approved for multiple applications making PLA suitable for expedited clinical translatability. These biomaterials can be fashioned into sutures, scaffolds, cell carriers, drug delivery systems, and a myriad of fabrications. PLA has been the focus of a multitude of preclinical and clinical testing. Three-dimensional printing has expanded the possibilities of biomedical engineering and has enabled the fabrication of a myriad of platforms for an extensive variety of applications. PLA has been widely used as temporary extracellular matrices in tissue engineering. At the other end of the spectrum, PLA's application as drug-loaded nanoparticle drug carriers, such as liposomes, polymeric nanoparticles, dendrimers, and micelles, can encapsulate otherwise toxic hydrophobic anti-tumor drugs and evade systemic toxicities. The clinical translation of these technologies from preclinical experimental settings is an ever-evolving field with incremental advancements. In this review, some of the biomedical applications of PLA and its copolymers are highlighted and briefly summarized. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Plasma protein corona modulates the vascular wall interaction of drug carriers in a material and donor specific manner.

    Directory of Open Access Journals (Sweden)

    Daniel J Sobczynski

    Full Text Available The nanoscale plasma protein interaction with intravenously injected particulate carrier systems is known to modulate their organ distribution and clearance from the bloodstream. However, the role of this plasma protein interaction in prescribing the adhesion of carriers to the vascular wall remains relatively unknown. Here, we show that the adhesion of vascular-targeted poly(lactide-co-glycolic-acid (PLGA spheres to endothelial cells is significantly inhibited in human blood flow, with up to 90% reduction in adhesion observed relative to adhesion in simple buffer flow, depending on the particle size and the magnitude and pattern of blood flow. This reduced PLGA adhesion in blood flow is linked to the adsorption of certain high molecular weight plasma proteins on PLGA and is donor specific, where large reductions in particle adhesion in blood flow (>80% relative to buffer is seen with ∼60% of unique donor bloods while others exhibit moderate to no reductions. The depletion of high molecular weight immunoglobulins from plasma is shown to successfully restore PLGA vascular wall adhesion. The observed plasma protein effect on PLGA is likely due to material characteristics since the effect is not replicated with polystyrene or silica spheres. These particles effectively adhere to the endothelium at a higher level in blood over buffer flow. Overall, understanding how distinct plasma proteins modulate the vascular wall interaction of vascular-targeted carriers of different material characteristics would allow for the design of highly functional delivery vehicles for the treatment of many serious human diseases.

  5. Development of biocompatible and VEGF-targeted paclitaxel nanodrugs on albumin and graphene oxide dual-carrier for photothermal-triggered drug delivery in vitro and in vivo.

    Science.gov (United States)

    Deng, Wentao; Qiu, Juhui; Wang, Shaoting; Yuan, Zhi; Jia, Yuefeng; Tan, Hailin; Lu, Jiru; Zheng, Ruqiang

    2018-01-01

    In this study, we performed the characterization and synthesis of biocompatible and targeted albumin and graphene oxide (GO) dual-carrier paclitaxel (PTX) nanoparticles for photothermal-triggered tumor therapy. PTX absorbed on GO nanosheets as cores were coated with human serum albumin (HSA), following surface conjugation with monoclonal antibodies (mAb) against vascular endothelial growth factor (VEGF; denoted as mAbVEGF) via polyethylene glycol linker to form targeted nanoparticles (PTX-GHP-VEGF). The spherical nanoparticles were 191±5 nm in size with good stability and biocompatibility. GO functioned as the first carrier and a near infrared absorber that can generate photothermal effects under 5-minute 808-nm laser irradiation to thermal trigger the release of PTX from the second carrier HSA nanoparticles. The mechanism of thermal-triggered drug release was also investigated preliminarily, in which the heat generated by GO induced swelling of PTX-GHP-VEGF nanoparticles which released the drugs. In vitro studies found that PTX-GHP-VEGF can efficiently target human SW-13 adrenocortical carcinoma cells as evaluated by confocal fluorescence microscopy as well as transmission electron microscopy, and showed an obvious thermal-triggered antitumor effect, mediated by apoptosis. Moreover, PTX-GHP-VEGF combined with near infrared irradiation showed specific tumor suppression effects with high survival rate after 100 days of treatment. PTX-GHP-VEGF also demonstrated high biosafety with no adverse effects on normal tissues and organs. These results highlight the remarkable potential of PTX-GHP-VEGF in photothermal controllable tumor treatment.

  6. Sustained clinical safety and efficacy of a biodegradable-polymer coated sirolimus-eluting stent in "real-world" practice: three-year outcomes of the CREATE (Multi-Center Registry of EXCEL Biodegradable Polymer Drug Eluting Stents) study.

    Science.gov (United States)

    Han, Yaling; Jing, Quanmin; Li, Yi; Yang, Lixia; Liu, Huiliang; Shang, Xiaoming; Jiang, Tiemin; Li, Zhanquan; Zhang, Hua; Yan, Gaoliang

    2012-02-01

    The CREATE is a post-marketing surveillance multicenter registry that demonstrated satisfactory angiographic and clinical (at 18 months) outcomes of a biodegradable polymer based sirolimus-eluting stent (EXCEL, JW Medical System, Weihai, China) for the treatment of patients in routine clinical practice. To evaluate the three-year clinical safety and efficacy outcomes in patients enrolled in the CREATE study. A total of 2077 all comers have been enrolled in the CREATE study at 59 centers from four countries. Recommended antiplatelet regimen was clopidogrel and aspirin for six months followed by chronic aspirin therapy. The prespecified primary outcome was the rate of major adverse cardiac events (MACE) at 12, 18, and 36 months. Clinical follow-up was completed in 2025 (97.5%) patients at three years. The average duration of clopidogrel treatment was 199.8 ± 52.7 days and 80.5% of discharged patients discontinued clopidogrel at six months. The cumulative rate of MACE was 4.5% and the rate of stent thrombosis was 1.53% at three years. At six months to three years, prolonged clopidogrel therapy (>6 months) was not beneficial in reducing cumulative hazards of MACE (3.4% vs. 3.1%, log rank P = 0.725) or stent thrombosis (1.5% vs. 0.6%, log rank P = 0.053). This study demonstrates sustained three-year clinical safety and efficacy of biodegradable polymer-based sirolimus-eluting stents when used with six months of dual antiplatelet therapy in a "real-world" setting. Copyright © 2011 Wiley Periodicals, Inc.

  7. Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model

    Science.gov (United States)

    Hu, Yu-Lan; Qi, Wang; Han, Feng; Shao, Jian-Zhong; Gao, Jian-Qing

    2011-01-01

    Background Although there are a number of reports regarding the toxicity evaluation of inorganic nanoparticles, knowledge on biodegradable nanomaterials, which have always been considered safe, is still limited. For example, the toxicity of chitosan nanoparticles, one of the most widely used drug/gene delivery vehicles, is largely unknown. In the present study, the zebrafish model was used for a safety evaluation of this nanocarrier. Methods Chitosan nanoparticles with two particle sizes were prepared by ionic cross-linking of chitosan with sodium tripolyphosphate. Chitosan nanoparticles of different concentrations were incubated with zebrafish embryos, and ZnO nanoparticles were used as the positive control. Results Embryo exposure to chitosan nanoparticles and ZnO nanoparticles resulted in a decreased hatching rate and increased mortality, which was concentration-dependent. Chitosan nanoparticles at a size of 200 nm caused malformations, including a bent spine, pericardial edema, and an opaque yolk in zebrafish embryos. Furthermore, embryos exposed to chitosan nanoparticles showed an increased rate of cell death, high expression of reactive oxygen species, as well as overexpression of heat shock protein 70, indicating that chitosan nanoparticles can cause physiological stress in zebrafish. The results also suggest that the toxicity of biodegradable nanocarriers such as chitosan nanoparticles must be addressed, especially considering the in vivo distribution of these nanoscaled particles. Conclusion Our results add new insights into the potential toxicity of nanoparticles produced by biodegradable materials, and may help us to understand better the nanotoxicity of drug delivery carriers. PMID:22267920

  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. Ab initio design of drug carriers for zoledronate guest molecule using phosphonated and sulfonated calix[4]arene and calix[4]resorcinarene host molecules

    Science.gov (United States)

    Jang, Yong-Man; Yu, Chol-Jun; Kim, Jin-Song; Kim, Song-Un

    2018-04-01

    Monomolecular drug carriers based on calix[n]-arenes and -resorcinarenes containing the interior cavity can enhance the affinity and specificity of the osteoporosis inhibitor drug zoledronate (ZOD). In this work we investigate the suitability of nine different calix[4]-arenes and -resorcinarenes based macrocycles as hosts for the ZOD guest molecule by conducting {\\it ab initio} density functional theory calculations for structures and energetics of eighteen different host-guest complexes. For the optimized molecular structures of the free, phosphonated, sulfonated calix[4]-arenes and -resorcinarenes, the geometric sizes of their interior cavities are measured and compared with those of the host-guest complexes in order to check the appropriateness for host-guest complex formation. Our calculations of binding energies indicate that in gaseous states some of the complexes might be unstable but in aqueous states almost all of the complexes can be formed spontaneously. Of the two different docking ways, the insertion of ZOD with the \\ce{P-C-P} branch into the cavity of host is easier than that with the nitrogen containing heterocycle of ZOD. The work will open a way for developing effective drug delivering systems for the ZOD drug and promote experimentalists to synthesize them.

  10. Particle size, surface hydrophobicity and interaction with serum of parenteral fat emulsions and model drug carriers as parameters related to RES uptake.

    Science.gov (United States)

    Carrstensen, H; Müller, R H; Müller, B W

    1992-10-01

    Fat emulsions for parenteral nutrition, stabilized by egg lecithin, were characterized in terms of parameters relevant to uptake by the reticuloendothelial system (RES), e.g. size distribution, surface hydrophobicity and adsorption of serum components as a measure of the degree of opsonization. Adsorption of serum components was quantified by zeta potential measurement. Fat emulsions for nutrition were compared with emulsions used for drug delivery and model drug carries for intravenous injection. The emulsions for drug delivery were stabilized by the blockcopolymers Poloxamer 188 and 407 (Pluronic F68 and F127) and Poloxamine 908. Model drug carriers were hydrophobic and hydrophilic polystyrene latex particles. Hydrophilic particles were prepared by adsorption of Poloxamine 908 (coating) onto the particle surface. The hydrophobicity and serum protein adsorption decreased from hydrophobic latex particles to egg lecithin emulsions and blockcopolymer emulsions and particles. The data correlated with that in the literature concerning liver uptake in vivo showing complete RES clearance of hydrophobic latex particles, reduced uptake of egg lecithin emulsions and avoidance of RES uptake by Poloxamine 908 coated particles.

  11. Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Ouyang; Tao, Yongxin; Qin, Yong [Advanced Catalysis and Green Manufacturing Collaborative Innovation Center, School of Petrochemical Engineering, Changzhou University, Changzhou 213164 (China); Chen, Chuanxiang [School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212003 (China); Pan, Yan; Deng, Linhong [Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou 213164 (China); Liu, Li [School of pharmaceutical Engineering & Life Science, Changzhou University, Changzhou 213164 (China); Kong, Yong, E-mail: yzkongyong@126.com [Advanced Catalysis and Green Manufacturing Collaborative Innovation Center, School of Petrochemical Engineering, Changzhou University, Changzhou 213164 (China)

    2016-10-01

    Highly fluorescent graphene quantum dots (GQDs)-chitosan (CS) hybrid xerogels (GQDs-CS) were facilely synthesized, and the morphology of GQDs-CS was controllable by varying the content of GQDs in the xerogel. The GQDs-CS exhibited a porous and three-dimensional (3D) network structure when the content of GQDs reached 43% (wt%) in the xerogel, which was beneficial for drug loading and sustained release. The as-prepared GQDs-CS could also be applied for in vivo imaging since it showed strong blue, green and red luminescence under excitation of varying wavelengths. Moreover, the pH-induced protonation/deprotonation of the –NH{sub 2} groups on CS chains can result in a pH-dependent drug delivery behavior of the GQDs-CS hybrid xerogel. - Graphical abstract: Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier. Display Omitted - Highlights: • Highly fluorescent GQDs-CS hybrid xerogels were facilely synthesized. • The as-made xerogels exhibited various morphologies with different GQDs contents. • The GQDs-CS exhibited a porous and 3D network when the content of GQDs reached 43%. • The GQDs-CS could be applied for in vivo imaging since it showed strong luminescence. • The protonation/deprotonation of –NH{sub 2} on CS result in a pH-dependent drug delivery.

  12. Silk Fibroin-Based Nanoparticles for Drug Delivery

    Science.gov (United States)

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

    2015-01-01

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

  13. A polymeric prodrug of 5-fluorouracil-1-acetic acid using a multi-hydroxyl polyethylene glycol derivative as the drug carrier.

    Directory of Open Access Journals (Sweden)

    Man Li

    Full Text Available Macromolecular prodrugs obtained by covalently conjugating small molecular drugs with polymeric carriers were proven to accomplish controlled and sustained release of the therapeutic agents in vitro and in vivo. Polyethylene glycol (PEG has been extensively used due to its low toxicity, low immunogenicity and high biocompatibility. However, for linear PEG macromolecules, the number of available hydroxyl groups for drug coupling does not change with the length of polymeric chain, which limits the application of PEG for drug conjugation purposes. To increase the drug loading and prolong the retention time of 5-fluorouracil (5-Fu, a macromolecular prodrug of 5-Fu, 5-fluorouracil-1 acid-PAE derivative (5-FA-PAE was synthesized and tested for the antitumor activity in vivo.PEG with a molecular weight of 38 kDa was selected to synthesize the multi-hydroxyl polyethylene glycol derivative (PAE through an addition reaction. 5-fluorouracil-1 acetic acid (5-FA, a 5-Fu derivative was coupled with PEG derivatives via ester bond to form a macromolecular prodrug, 5-FA-PAE. The in vitro drug release, pharmacokinetics, in vivo distribution and antitumor effect of the prodrug were investigated, respectively.The PEG-based prodrug obtained in this study possessed an exceedingly high 5-FA loading efficiency of 10.58%, much higher than the maximum drug loading efficiency of unmodified PEG with the same molecular weight, which was 0.98% theoretically. Furthermore, 5-FA-PAE exhibited suitable sustained release in tumors.This study provides a new approach for the development of the delivery to tumors of anticancer agents with PEG derivatives.

  14. Preparation and characterization of Fe3O4-Ag2O quantum dots decorated cellulose nanofibers as a carrier of anticancer drugs for skin cancer.

    Science.gov (United States)

    Fakhri, Ali; Tahami, Shiva; Nejad, Pedram Afshar

    2017-10-01

    The Best performance drug delivery systems designed with Fe 3 O 4 -Ag 2 O quantum dots decorated cellulose nanofibers which that grafted with Etoposide and Methotrexate. Morphology properties were characterized by Scanning and Transmittance electron microscopy. The crystalline structure of prepared sample was evaluated using by X-ray diffraction. The vibrating sample magnetometer analysis was used for magnetic behavior of samples. The size distributions of Fe 3 O 4 -Ag 2 O QDs/Cellulose fibers nanocomposites indicate that the average diameter was 62.5nm. The Saturation magnetization (Ms) indicates the Fe 3 O 4 -Ag 2 O QDs/Cellulose fibers nanocomposites have ferromagnetic properties in nature. For make carrier, the Iron and Silver should be binds to cellulose nanofibers and to drug molecules and observe in UV-vis spectroscopy. The drug release kinetics was studied in vitro as spectrophotometrically. The release of Etoposide and Methotrexate were carried out with a constant speed, and the equilibrium reached at 24 and 30h with a total amount 78.94% and 63.84%, respectively. The results demonstrated that the obtained Fe 3 O 4 -Ag 2 O quantum dots/cellulose fibers nanocomposites could be applied for drug delivery systems. Cytotoxicity and antioxidant study confirmed the activity of the drug incorporated in nanocomposites. In addition, the cytotoxicity of drug was increased when loaded on nanocomposites, compared to pure Fe 3 O 4 -Ag 2 O quantum dots/cellulose fibers nanocomposites. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers.

    Science.gov (United States)

    Lin, Chih-Hung; Chen, Chun-Han; Lin, Zih-Chan; Fang, Jia-You

    2017-04-01

    Chemical and enzymatic barriers in the gastrointestinal (GI) tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs) are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs. Copyright © 2017. Published by Elsevier B.V.

  16. Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers

    Directory of Open Access Journals (Sweden)

    Chih-Hung Lin

    2017-04-01

    Full Text Available Chemical and enzymatic barriers in the gastrointestinal (GI tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs.

  17. Liver cancer cells: targeting and prolonged-release drug carriers consisting of mesoporous silica nanoparticles and alginate microspheres.

    Science.gov (United States)

    Liao, Yu-Te; Liu, Chia-Hung; Yu, Jiashing; Wu, Kevin C-W

    2014-01-01

    A new microsphere consisting of inorganic mesoporous silica nanoparticles (MSNs) and organic alginate (denoted as MSN@Alg) was successfully synthesized by air-dynamic atomization and applied to the intracellular drug delivery systems (DDS) of liver cancer cells with sustained release and specific targeting properties. MSN@Alg microspheres have the advantages of MSN and alginate, where MSN provides a large surface area for high drug loading and alginate provides excellent biocompatibility and COOH functionality for specific targeting. Rhodamine 6G was used as a model drug, and the sustained release behavior of the rhodamine 6G-loaded MSN@Alg microspheres can be prolonged up to 20 days. For targeting therapy, the anticancer drug doxorubicin was loaded into MSN@Alg microspheres, and the (lysine)4-tyrosine-arginine-glycine-aspartic acid (K4YRGD) peptide was functionalized onto the surface of MSN@Alg for targeting liver cancer cells, hepatocellular carcinoma (HepG2). The results of the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and confocal laser scanning microscopy indicate that the MSN@Alg microspheres were successfully uptaken by HepG2 without apparent cytotoxicity. In addition, the intracellular drug delivery efficiency was greatly enhanced (ie, 3.5-fold) for the arginine-glycine-aspartic acid (RGD)-labeled, doxorubicin-loaded MSN@Alg drug delivery system compared with the non-RGD case. The synthesized MSN@Alg microspheres show great potential as drug vehicles with high biocompatibility, sustained release, and targeting features for future intracellular DDS.

  18. Formulation and In-vitro Evaluation of Tretinoin Microemulsion as a Potential Carrier for Dermal Drug Delivery

    Science.gov (United States)

    Mortazavi, Seyed Alireza; Pishrochi, Sanaz; Jafari azar, Zahra

    2013-01-01

    In this study, tretinoin microemulsion has been formulated based on phase diagram studies by changing the amounts and proportions of inactive ingredients, such as surfactants, co-surfactants and oils. The effects of these variables have been determined on microemulsion formation, particle size of the dispersed phase and release profile of tretinoin from microemulsion through dialysis membrane. In released studies, static Franz diffusion cells mounted with dialysis membrane were used. Sampling was conducted every 3 h at room temperature over a period of 24 h. The amount of released drug was measured with UV-spectrophotometer and the percentage of drug released was calculated. Based on the results obtained, the oil phase concentration had a proportional effect on particle size which can consequently influence on drug release. The particle size and the amount of released drug were affected by the applied surfactants. The components of the optimized microemulsion formulation were 15% olive oil, 12% propylene glycol (as co-surfactant), 33% Tween®80 (as surfactant) and 40% distilled water, which was tested for viscosity and rheological behavior. The prepared tretinoin microemulsion showed pseudoplastic-thixotropic behavior. The profile of drug release follows zero order kinetics. The optimized tretinoin microemulsion showed enhanced in-vitro release profile compared to the commercial gels and creams. PMID:24523740

  19. Facile preparation of magnetic metal organic frameworks core–shell nanoparticles for stimuli-responsive drug carrier

    Science.gov (United States)

    Li, Sheng; Bi, Ke; Xiao, Ling; Shi, Xiaowen

    2017-12-01

    Facile synthesis of core–shell magnetic MOFs for drug delivery is of significance due to the advantages of high drug load and easy separation. In this work, magnetic metal organic frameworks (MOFs, Fe3O4-NH2@MIL101-NH2) core–shell nanoparticles were synthesized rapidly in water phase by microwave irradiation using Fe3+ and 2-amino-1,4-benzenedicarboxylate (BDC-NH2) as metal ions and ligands respectively. The resulting magnetic MOFs exhibit large surface areas (96.04 m2 g‑1), excellent magnetic response (20.47 emu g‑1) and large mesopore volume (22.07 cm3 g‑1) along with spherical morphologies with the diameters ranging from 140–330 nm. Using doxorubicin (DOX) as a model drug, the drug loading capacity of Fe3O4-NH2@MIL101-NH2 could reach 36.02%, substantially higher than pristine MIL101-NH2. Importantly, the release of DOX could be controlled by pH as well as the meso pore size of MOFs. The cytotoxicity assay showed that the magnetic MOFs have low cytotoxicity and good biocompatibility. The results suggest great potential of the magnetic MOFs core–shell nanoparticles fabricated in this study on controlled drug release of DOX.

  20. p-Hydroxy benzoic acid-conjugated dendrimer nanotherapeutics as potential carriers for targeted drug delivery to brain: an in vitro and in vivo evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Swami, Rajan; Singh, Indu [National Institute of Pharmaceutical Education & Research (NIPER), Department of Pharmaceutics (India); Kulhari, Hitesh [CSIR-Indian Institute of Chemical Technology, Medicinal Chemistry & Pharmacology Division (India); Jeengar, Manish Kumar [National Institute of Pharmaceutical Education & Research (NIPER), Departmentof Pharmacology (India); Khan, Wahid, E-mail: wahid@niperhyd.ac.in; Sistla, Ramakrishna, E-mail: sistla@iict.res.in, E-mail: rksistla@yahoo.com [National Institute of Pharmaceutical Education & Research (NIPER), Department of Pharmaceutics (India)

    2015-06-15

    Dendrimers which are discrete nanostructures/nanoparticles are emerging as promising candidates for many nanomedicine applications. Ligand-conjugated dendrimer facilitate the delivery of therapeutics in a targeted manner. Small molecules such as p-hydroxyl benzoic acid (pHBA) were found to have high affinity for sigma receptors which are prominent in most parts of central nervous system and tumors. The aim of this study was to synthesize pHBA-dendrimer conjugates as colloidal carrier for site-specific delivery of practically water insoluble drug, docetaxel (DTX) to brain tumors and to determine its targeting efficiency. pHBA, a small molecule ligand was coupled to the surface amine groups of generation 4-PAMAM dendrimer via a carbodiimide reaction and loaded with DTX. The conjugation was confirmed by {sup 1}HNMR and FT-IR spectroscopy. In vitro release of drug from DTX-loaded pHBA-conjugated dendrimer was found to be less as compared to unconjugated dendrimers. The prepared drug delivery system exhibited good physico-chemical stability and decrease in hemolytic toxicity. Cell viability and cell uptake studies were performed against U87MG human glioblastoma cells and formulations exerted considerable anticancer effect than plain drug. Conjugation of dendrimer with pHBA significantly enhanced the brain uptake of DTX which was shown by the recovery of a higher percentage of the dose from the brain following administration of pHBA-conjugated dendrimers compared with unconjugated dendrimer or formulation in clinical use (Taxotere{sup ®}). Therefore, pHBA conjugated dendrimers could be an efficient delivery vehicle for the targeting of anticancer drugs to brain tumors.

  1. Tocopheryl phosphate mixture (TPM) as a novel lipid-based transdermal drug delivery carrier: formulation and evaluation.

    Science.gov (United States)

    Gavin, Paul D; El-Tamimy, Mahmoud; Keah, Hooi Hong; Boyd, Ben J

    2017-02-01

    Transdermal drug delivery is a useful route of administration that avoids first-pass metabolism and more invasive delivery options. However, many drugs require enhancers to enable sufficient drug absorption to reach therapeutic effect. Alpha-tocopheryl phosphate (TP) and di-alpha-tocopheryl phosphate (T2P) are two phosphorylated forms of vitamin E which form tocopheryl phosphate mixture (TPM) when combined, and have been proposed to enhance the dermal and transdermal delivery of actives of interest. Here, we report the physicochemical characteristics and morphological properties of TPM formulations, including particle size, deformability and morphology, and its ability to facilitate the transport of carnosine, vitamin D3, CoEnzyme Q10 and caffeine into, and across, the skin. Results demonstrate that TPM self-assembles to form vesicular structures in hydroethanolic solutions ranging in mean size from 101 to 162 nM depending on the amount of TPM and ethanol present in the formulation. The ratio of TP to T2P in TPM formulations altered vesicle size and elasticity, with vesicles high in TP found to be more deformable than those rich in T2P. TPM produced a significant (p TPM delivery platform was able to deliver a diverse range of actives with differing size and solubility profiles and therefore has significant potential to expand the number and types of drugs available for topical application and transdermal delivery.

  2. Sodium Alginate with PEG/PEO Blends as a Floating Drug Delivery Carrier – In vitro Evaluation

    Directory of Open Access Journals (Sweden)

    Christe Sonia Mary

    2016-09-01

    Full Text Available Purpose: Floating drug delivery system reduces the quantity of drug intake and the risk of overloading the organs with excess drug. Methods: In the present study, we prepared the blends of sodium alginate with polyethylene glycol (PEG and polyethylene oxide (PEO as a matrix, sodium hydrogen carbonate as a pore forming agent, methyl cellulose as a binder and barium chloride containing 10% acetic acid as a hardening agent. Different ratios of pore forming agent to the polymer blend was used to prepare the floating beads with different porosity and morphology. Ciprofloxacin hydrochloride was used as a model drug for the release kinetics studies. Results: The beads were characterized by optical and FESEM microscopy to study the morphology and pore dimensions. The results obtained shows decrease in beads size with increase in the concentration of the pore forming agent. The swelling properties of the beads were found to be in the range of 80% to 125%. The release kinetics of the ciprofloxacin from the beads was measured by UV-Visible spectroscopy at λmax of 278nm and the results shows for highly porous beads. Conclusion: By varying the amount of alginate and pore forming agent the release kinetics is found to get altered. As a result, ciprofloxacin hydrochloride release is found to be sustained from the blended beads.

  3. Natural gum modified emulsion gel as single carrier for the oral delivery of probiotic-drug combination.

    Science.gov (United States)

    Pandey, S; Senthilguru, K; Uvanesh, K; Sagiri, S S; Behera, B; Babu, N; Bhattacharyya, M K; Pal, K; Banerjee, I

    2016-11-01

    Single formulation based delivery of probiotic-drug combination is envisioned as a superior therapeutic delivery modality for the diseases like Crohn's diseases, ulceritive colitis and Recurrent Clostridium difficile-Associated Diarrhoea (RCDAD). Keeping this perspective in mind, here we have developed natural gum [using a combination of aqueous solution of xantham gum (X) and guar gum (G)] modified sunflower oil based emulsion gels for the delivery of probiotics-drugs combination. FT-IR analysis and fluorescence microscopy together confirmed the formation of oil-in-water type emulsion gel by physical gelation in presence of the physical gelator sorbitan monopalmitate (SM). Other studies (XRD, DSC, mechanical properties and disintegration study) revealed that the variation in relative proportion of the two gums has a sporadic but significant effect on the physico-chemical properties of the gel. Post storage viability of commercially used probiotic Lactobacillus plantarum 299v (Lp 299v) at different storage conditions (4°C, -20°C, -196°C) was found higher in the emulsion gels with respect to the control. Moreover, the gels were found suitable for sustained delivery of metronidazole (the lipophilic drug often used with Lp 299v). In conclusion, the natural gum modified emulsion gel may be used as a delivery system for the probiotic-drug combination. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Potentials and limitations of the low-molecular-weight protein lysozyme as a carrier for renal drug targeting

    NARCIS (Netherlands)

    Haverdings, RFG; Haas, M; Greupink, AR; de Vries, PAM; Moolenaar, F; de Zeeuw, D; Meijer, DKF

    2001-01-01

    Selective targeting of drugs to the kidney may enable an increased renal effectiveness combined with a reduction of extrarenal toxicity. Intrarenal delivery to the proximal tubular cell can be achieved using low-molecular-weight proteins, such as lysozyme. Administration of high dosages of lysozyme,

  5. Modified human serum albumins as carriers for the specific delivery of antiviral drugs to liver- and blood cells

    NARCIS (Netherlands)

    Jansen, Robert Walter

    1992-01-01

    The general goal of this study, was to determine the possibility of a targeted delivery of antiviral drugs to their site of action. We decided to focus on two viral diseases; HIV and Hepatitis B, that replicate in T,-lymphocytes, monocytes/macrophages and hepatocytes respectively. The specific aims

  6. The Use of Multi-Walled Carbon Nanotubes as Possible Carrier in Drug Delivery System for Aspirin

    Science.gov (United States)

    Yusof, Alias Mohd.; Buang, Nor Aziah; Yean, Lee Sze; Ibrahim, Mohd. Lokman

    2009-06-01

    Carbon nanotubes (CNTs) have raised great interest in a number of applications, including field emission, energy storage, molecular electronics, sensors, biochips and drug delivery systems. This is due to their remarkable mechanical properties, chemical stability and biofunctionalizability. This nanomaterial is low in weight, has high strength and a high aspect ratio (long length compared to a small diameter). This paper will present a brief overview of drugs adsorbed onto the surface of carbon nanotubes via sonication method. The surface area of carbon nanotubes was measured by methylene blue method, Carbon nanotubes synthesized by catalytic chemical vapor deposition (CCVD) method were purified and functionalized in a mixture of concentrated acids (H2SO4:HNO3 = 3:1) at room temperature (25° C) via sonication in water bath, yielding carboxylic acid group on the CNTs' surface. CNT was successfully loaded with 48 %(w/w) aspirin molecules by suspending CNTs in a solution of aspirin in alcohol. Analysis of loaded CNTs by Field Emission-Scanning Electron Microscope (FESEM), Fourier Transform Infrared Spectrum (FITR) and UV-visible Spectroscopy confirmed the loading of the drug onto the CNTs. The work presented is a prelude to the direction of using carbon nanotubes as a drug delivery system to desired sites in human body.

  7. Liver cancer cells: targeting and prolonged-release drug carriers consisting of mesoporous silica nanoparticles and alginate microspheres

    Directory of Open Access Journals (Sweden)

    Liao YT

    2014-06-01

    Full Text Available Yu-Te Liao,1 Chia-Hung Liu,2 Jiashing Yu,1 Kevin C-W Wu1,3 1Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan; 2Department of Urology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; 3Division of Medical Engineering Research, National Health Research Institutes, Zhunan Township, Miaoli County, Taiwan Abstract: A new microsphere consisting of inorganic mesoporous silica nanoparticles (MSNs and organic alginate (denoted as MSN@Alg was successfully synthesized by air-dynamic atomization and applied to the intracellular drug delivery systems (DDS of liver cancer cells with sustained release and specific targeting properties. MSN@Alg microspheres have the advantages of MSN and alginate, where MSN provides a large surface area for high drug loading and alginate provides excellent biocompatibility and COOH functionality for specific targeting. Rhodamine 6G was used as a model drug, and the sustained release behavior of the rhodamine 6G-loaded MSN@Alg microspheres can be prolonged up to 20 days. For targeting therapy, the anticancer drug doxorubicin was loaded into MSN@Alg microspheres, and the (lysine4-tyrosine-arginine-glycine-aspartic acid (K4YRGD peptide was functionalized onto the surface of MSN@Alg for targeting liver cancer cells, hepatocellular carcinoma (HepG2. The results of the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT assay and confocal laser scanning microscopy indicate that the MSN@Alg microspheres were successfully uptaken by HepG2 without apparent cytotoxicity. In addition, the intracellular drug delivery efficiency was greatly enhanced (ie, 3.5-fold for the arginine-glycine-aspartic acid (RGD-labeled, doxorubicin-loaded MSN@Alg drug delivery system compared with the non-RGD case. The synthesized MSN@Alg microspheres show great potential as drug vehicles with high biocompatibility, sustained release, and targeting features for future intracellular DDS. Keywords

  8. In vitro gentamicin release from commercially available calcium-phosphate bone substitutes influence of carrier type on duration of the release profile

    Directory of Open Access Journals (Sweden)

    Bronckers Antonius LJJ

    2006-02-01

    Full Text Available Abstract Background Polymethyl-methacrylate (PMMA beads releasing antibiotics are used extensively to treat osteomyelitis, but require surgical removal afterwards because they do not degrade. Methods As an alternative option, this report compares the in vitro gentamicin release profile from clinically used, biodegradable carrier-materials: six injectable cements and six granule-types. Cement cylinders and coated granules containing 3% gentamicin were submerged in dH2O and placed in a 48-sample parallel drug-release system. At regular intervals (30, 90, 180 min. and then every 24 h, for 21 days, the release fluid was exchanged and the gentamicin concentration was measured. The activity of released gentamicin was tested on Staphylococcus aureus. Results All combinations showed initial burst-release of active gentamicin, two cements had continuous-release (17 days. The relative release of all cements (36–85% and granules (30–62% was higher than previously reported for injectable PMMA-cements (up to 17% and comparable to other biodegradable carriers. From the cements residual gentamicin could be extracted, whereas the granules released all gentamicin that had adhered to the surface. Conclusion The high release achieved shows great promise for clinical application of these biodegradable drug-carriers. Using the appropriate combination, the required release profile (burst or sustained may be achieved.

  9. AlPcS4-PDT for gastric cancer therapy using gold nanorod, cationic liposome, and Pluronic® F127 nanomicellar drug carriers.

    Science.gov (United States)

    Xin, Jing; Wang, Sijia; Wang, Bing; Wang, Jiazhuang; Wang, Jing; Zhang, Luwei; Xin, Bo; Shen, Lijian; Zhang, Zhenxi; Yao, Cuiping

    2018-01-01

    As a promising photodynamic therapy (PDT) agent, Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS 4 ) provides deep penetration into tissue, high quantum yields, good photostability, and low photobleaching. However, its low delivery efficiency and high binding affinity to serum albumin cause its low penetration into cancer cells, further limiting its PDT effect on gastric cancer. In order to improve AlPcS 4 /PDT effect, the AlPcS 4 delivery sys tems with different drug carriers were synthesized and investigated. Gold nanorods, cationic liposomes, and Pluronic ® F127 nanomicellars were used to formulate the AlPcS 4 delivery systems. The anticancer effect was evaluated by CCK-8 assay and colony formation assay. The delivery efficiency of AlPcS 4 and the binding affinity to serum proteins were determined by fluorescence intensity assay. The apoptosis and necrosis ability, reactive oxygen species and singlet oxygen generation, mitochondrial transmembrane potential and ([Ca 2+ ] i ) concentration were further measured to evaluate the mechanism of cell death. The series of synthesized AlPcS 4 delivery systems with different drug carriers improve the limited PDT effect in varying degrees. In contrast, AlPcS 4 complex with gold nanorods has significant anticancer effects because gold nanorods are not only suitable for AlPcS 4 delivery, but also exhibit enhanced singlet oxygen generation effect and photothermal effect to induce cell death directly. Moreover, AlPcS 4 complex with cationic liposomes shows the potent inhibition effect because of its optimal AlPcS 4 delivery efficiency and ability to block serum albumin. In addition, AlPcS 4 complex with Pluronic F127 exhibits inferior PDT effect but presents lower cytotoxicity, slower dissociation rate, and longer retention time of incorporated drugs; thus, F127-AlPcS 4 is used for prolonged gastric cancer therapy. The described AlPcS 4 drug delivery systems provide promising agents for gastric cancer therapy.

  10. Permeation measurement of gestodene for some biodegradable materials using Franz diffusion cells.

    Science.gov (United States)

    Liu, Danhua; Zhang, Chong; Zhang, Xiaowei; Zhen, Zhu; Wang, Ping; Li, Jianxin; Yi, Dongxu; Jin, Ying; Yang, Dan

    2015-09-01

    Biodegradable poly(d,l-lactide) (PDLLA), Poly(trimethylene carbonate) (PTMC), polycaprolactone (PCL), poly(caprolactone-co-d,l-lactide) (PCDLLA) and poly(trimethylene carbonate-co-caprolactone) (PTCL) are recently used for clinical drug delivery system such as subcutaneous contraceptive implant capsule due to their biodegradable properties that they could possess long-term stable performance in vivo without removal, however their permeation rate is unknown. In the work, biodegradable material membranes were prepared by solvent evaporation using chloroform, and commercial silicone rubber membrane served as a control. Gestodene was used as a model drug. Gestodene has high biologic progestational activity which allows for high contraceptive reliability at very low-dose levels. The permeation rate of gestodene for several biodegradable materials was evaluated. In vitro diffusion studies were done using Franz diffusion cells with a diffusion area of 1.33 cm(2). Phosphate buffer solution (PBS, pH 7.4), 10% methanol solution and distilled water were taken in donor and receiver chambers at temperature of 37 °C respectively. The in vitro experiments were conducted over a period of 24 h during which samples were collected at regular intervals. The withdrawn samples were appropriately diluted and measured on UV-vis spectrophotometer at 247 nm. Conclusion data from our study showed that permeation rate of PCDLLA with CL ratio more than 70% could be more excellent than commercial silicone rubber membrane. They may be suitable as a candidate carrier for gestodene subcutaneous contraceptive implants in contraceptive fields.

  11. Principal Physicochemical Methods Used to Characterize Dendrimer Molecule Complexes Used as Genetic Therapy Agents, Nanovaccines or Drug Carriers.

    Science.gov (United States)

    Alberto, Rodríguez Fonseca Rolando; Joao, Rodrigues; de Los Angeles, Muñoz-Fernández María; Alberto, Martínez Muñoz; Manuel Jonathan, Fragoso Vázquez; José, Correa Basurto

    2017-08-30

    Nanomedicine is the application of nanotechnology to medicine. This field is related to the study of nanodevices and nanomaterials applied to various medical uses, such as in improving the pharmacological properties of different molecules. Dendrimers are synthetic nanoparticles whose physicochemical properties vary according to their chemical structure. These molecules have been extensively investigated as drug nanocarriers to improve drug solubility and as sustained-release systems. New therapies such as gene therapy and the development of nanovaccines can be improved by the use of dendrimers. The biophysical and physicochemical characterization of nucleic acid/peptide-dendrimer complexes is crucial to identify their functional properties prior to biological evaluation. In that sense, it is necessary to first identify whether the peptide-dendrimer or nucleic aciddendrimer complexes can be formed and whether the complex can dissociate under the appropriate conditions at the target cells. In addition, biophysical and physicochemical characterization is required to determine how long the complexes remain stable, what proportion of peptide or nucleic acid is required to form the complex or saturate the dendrimer, and the size of the complex formed. In this review, we present the latest information on characterization systems for dendrimer-nucleic acid, dendrimer-peptide and dendrimer-drug complexes with several biotechnological and pharmacological applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Radionuclide carriers

    International Nuclear Information System (INIS)

    Hartman, F.A.; Kretschmar, H.C.; Tofe, A.J.

    1977-01-01

    The invention provides physiologically acceptable particulate radionuclide carriers comprising a reducing agent bound to an anionic starch derivative, useful in the preparation of organ-specific diagnostic radiopharmaceuticals

  13. Enhanced antitumoral activity of doxorubicin against lung cancer cells using biodegradable poly(butylcyanoacrylate nanoparticles

    Directory of Open Access Journals (Sweden)

    Melguizo C

    2015-12-01

    Full Text Available Consolación Melguizo1,2,* Laura Cabeza,1,* Jose Prados,1,2 Raúl Ortiz,1,3 Octavio Caba,1,3 Ana R Rama,1,3 Ángel V Delgado,4 José L Arias1,2,5 1Institute of Biopathology and Regenerative Medicine (IBIMER, Biomedical Research Center, 2Biosanitary Institute of Granada (IBS Granada, SAS Universidad de Granada, Granada, 3Department of Health Science, University of Jaén, Jaén, 4Department of Applied Physics, 5Department of Pharmacy and Pharmaceutical Technology, University of Granada, Granada, Spain *These authors contributed equally to this work Abstract: Doxorubicin (Dox is widely used for the combined chemotherapy of solid tumors. However, the use of these drug associations in lung cancer has low antitumor efficacy. To improve its efficacious delivery and activity in lung adenocarcinoma cells, we developed a biodegradable and noncytotoxic nanoplatform based on biodegradable poly(butylcyanoacrylate (PBCA. The reproducible formulation method was based on an anionic polymerization process of the PBCA monomer, with the antitumor drug being entrapped within the nanoparticle (NP matrix during its formation. Improved drug-entrapment efficiencies and sustained (biphasic drug-release properties were made possible by taking advantage of the synthesis conditions (drug, monomer, and surfactant-agent concentrations. Dox-loaded NPs significantly enhanced cellular uptake of the drug in the A549 and LL/2 lung cancer cell lines, leading to a significant improvement of the drug’s antitumoral activity. In vivo studies demonstrated that Dox-loaded NPs clearly reduced tumor volumes and increased mouse-survival rates compared to the free drug. These results demonstrated that PBCA NPs may be used to optimize the antitumor activity of Dox, thus exhibiting a potential application in chemotherapy against lung adenocarcinoma. Keywords: lung cancer, cancer chemotherapy, PBCA, polymeric nanoparticles, drug carrier

  14. 131I-Traced PLGA-Lipid Nanoparticles as Drug Delivery Carriers for the Targeted Chemotherapeutic Treatment of Melanoma

    Science.gov (United States)

    Wang, Haiyan; Sheng, Weizhong

    2017-05-01

    Herein, folic acid (FA) conjugated Poly(d,l-lactide-co-glycolide) (PLGA)-lipid composites (FA-PL) were developed as nanocarriers for the targeted delivery of insoluble anti-cancer drug paclitaxel (PTX), resulting FA-PLP nanoparticles. Furthermore, 131I, as a radioactive tracer, was used to label FA-PLP nanoparticles (FA-PLP-131I) to evaluate their cell uptake activity, in vivo blood circulation, and biodistribution. The FA-PLP-131I nanoparticles had a spherical morphology with great stability, a narrow size distribution (165.6 and 181.2 nm), and -22.1 mV in average zeta potential. Confocal laser scanning microscopy indicated that the targeting molecule FA promotes PLP-131I uptake by melanoma B16F10 cells, which was further confirmed by the cell incorporation rate via 131I activity detection as measured by a gamma counter. FA-PLP-131I without PTX (FA-PL-131I) shows minor cytotoxicity, good biocompatibility, while FA-PLP-131I was demonstrated to have efficient cell viability suppression compared to free PTX and PLP-131I. Following intravenous injection, the blood circulation half-life of free PTX ( t 1/2 = 5.4 ± 0.23 h) was prolonged to 18.5 ± 0.5 h by FA-PLP-131I. Through FA targeting, the tumor uptake of FA-PLP-131I was approximately 4.41- and 12.8-fold higher compared to that of PLP-131I and free PTX-131I, respectively. Moreover, following 40 days of treatment, FA-PLP-131I showed an improved tumor inhibition effect compared to free PTX and PLP-131I, with no relapse and no remarkable systemic in vivo toxicity. The results demonstrate that the 131I-labeled PLGA-lipid nanoparticle can be simultaneously applied for targeted drug delivery and reliable tracking of drugs in vivo.

  15. Superparamagnetic anisotropic nano-assemblies with longer blood circulation in vivo: a highly efficient drug delivery carrier for leukemia therapy.

    Science.gov (United States)

    Xiong, Fei; Tian, Jilai; Hu, Ke; Zheng, Xiawen; Sun, Jianfei; Yan, Caiyun; Yao, Juan; Song, Lina; Zhang, Yu; Gu, Ning

    2016-10-06

    Leukemia, unlike solid tumors, has no definite shape and spreads throughout the whole circulatory system, therefore the therapy of leukemia requires medication to stay longer in the circulatory system. Anisotropic nanoparticles, showing longer blood circulating life than that of isotropic nanoparticles reported in previous research, meet the demands of leukemia therapy. Based on this strategy, superparamagnetic anisotropic nano-assemblies (SANs) were fabricated and loaded with vincristine (VCR) to form VCR-SANs. When compared to the same dose of VCR-loaded isotropic nano-assemblies (SINs), the decrease in the leukocytes count and the positive expression ratio of CD13 in the VCR-SANs group were 19.38% and 16.4%, respectively, which indicated the improved anti-leukemia activity of the VCR-SANs. From the results of the pharmacokinetics study, the VCR-SANs remarkably held the amount of drug removed from the whole body per unit time half of the isotropic group and the concentration of drug in blood plasma against time was 2.1 times the isotropic group, demonstrating the rapid and sustained release behavior and longer blood circulation when combined with the results of in vivo tissue distribution studies. In summary, anisotropic nano-assemblies were found to be more promising than isotropic nano-assemblies via our in vivo and in vitro examinations.

  16. Radionuclide carriers

    International Nuclear Information System (INIS)

    Hartman, F.A.; Kretschmar, H.C.

    1976-01-01

    A new carrier for radionuclide technetium 99m has been prepared for scintiscanning purposes. The new preparate consists of physiologically acceptable water-insoluble Tcsup(99m)-carrier containing from 0.2 to 0.8 weight percent of stannic ion as reductor, bound to an anionic starch derivative with about 1-20% of phosphate substituents. (EG)

  17. Aminoclay–lipid hybrid composite as a novel drug carrier of fenofibrate for the enhancement of drug release and oral absorption

    Directory of Open Access Journals (Sweden)

    Yang L

    2016-03-01

    Full Text Available Liang Yang, Yating Shao, Hyo-Kyung Han BK Plus Project Team, College of Pharmacy, Dongguk University, Goyang, South Korea Abstract: This study aimed to prepare the aminoclay–lipid hybrid composite to enhance the drug release and improve the oral bioavailability of poorly water-soluble fenofibrate. Antisolvent precipitation coupled with an immediate freeze-drying method was adopted to incorporate fenofibrate into aminoclay–lipid hybrid composite (ALC. The optimal composition of the ALC formulation was determined as the ratios of aminoclay to krill oil of 3:1 (w/w, krill oil to fenofibrate of 2:1 (w/w, and antisolvent to solvent of 6:4 (v/v. The morphological characteristics of ALC formulation were determined using scanning electron microscopy, differential scanning calorimetry, and X-ray powder diffraction, which indicated microcrystalline state of fenofibrate in ALC formulation. The ALC formulation achieved almost complete dissolution within 30 minutes, whereas the untreated powder and physical mixture exhibited less than 15% drug release. Furthermore, ALC formulation effectively increased the peak plasma concentration (Cmax and area under the curve (AUC of fenofibric acid (an active metabolite in rats by approximately 13- and seven-fold, respectively. Furthermore, ALC formulation exhibited much lower moisture sorption behavior than the lyophilized formulation using sucrose as a cryoprotectant. Taken together, the present findings suggest that ALC formulation is promising for improving the oral absorption of poorly soluble fenofibrate. Keywords: aminoclay, omega-3 phospholipids, fenofibrate, drug release, oral absorption 

  18. 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.

  19. Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier

    Science.gov (United States)

    Tian, Shuangyan; Li, Juan; Tao, Qi; Zhao, Yawen; Lv, Zhufen; Yang, Fan; Duan, Haoyun; Chen, Yanzhong; Zhou, Qingjun; Hou, Dongzhi

    2018-01-01

    Background Glaucoma is a serious eye disease that can lead to loss of vision. Unfortunately, effective treatments are limited by poor bioavailability of antiglaucoma medicine due to short residence time on the preocular surface. Materials and methods To solve this, we successfully prepared novel controlled-release ion-exchange microparticles to deliver betaxolol hydrochloride (BH). Montmorillonite/BH complex (Mt-BH) was prepared by acidification-intercalation, and this complex was encapsulated in microspheres (Mt-BH encapsulated microspheres [BMEMs]) by oil-in-oil emulsion–solvent evaporation method. The BH loaded into ion-exchange Mt was 47.45%±0.54%. After the encapsulation of Mt-BH into Eudragit microspheres, the encapsulation efficiency of BH into Eudragit microspheres was 94.35%±1.01% and BH loaded into Eudragit microspheres was 14.31%±0.47%. Results Both Fourier transform infrared spectra and X-ray diffraction patterns indicated that BH was successfully intercalated into acid-Mt to form Mt-BH and then Mt-BH was encapsulated into Eudragit microspheres to obtain BMEMs. Interestingly, in vitro release duration of the prepared BMEMs was extended to 12 hours, which is longer than both of the BH solution (2.5 hours) and the conventional BH microspheres (5 hours). Moreover, BMEM exhibited lower toxicity than that of BH solution as shown by the results of cytotoxicity tests, chorioallantoic membrane-trypan blue staining, and Draize rabbit eye test. In addition, both in vivo and in vitro preocular retention capacity study of BMEMs showed a prolonged retention time. The pharmacodynamics showed that BMEMs could extend the drug duration of action. Conclusion The developed BMEMs have the potential to be further applied as ocular drug delivery systems for the treatment of glaucoma. PMID:29391798

  20. Design and evaluation of mPEG-PLA micelles functionalized with drug-interactive domains as improved drug carriers for docetaxel delivery.

    Science.gov (United States)

    Qi, Dingqing; Gong, Feirong; Teng, Xin; Ma, Mingming; Wen, Huijing; Yuan, Weihao; Cheng, Yi; Lu, Chong

    2017-10-01

    Polymeric micelles are very attractive drug delivery systems for hydrophobic agents, owing to their readily tailorable chemical structure and ease for scale-up preparation. However, the intrinsic poor stability of drug-loaded micelles presents one of the major challenges for most micellar systems in the translation to clinical applications. In this study, a simple, well-defined, and easy-to-scale up 9-Fluorenylmethoxycarbonyl (Fmoc) and tert-butoxycarbonyl (Boc) containing lysine dendronized mPEG-PLA (mPEG-PLA-Lys(FB) 2 ) micellar formulation was designed and prepared for docetaxel (DTX) delivery, in an effort to improve the stability of the micelles, and its physicochemical properties, pharmacokinetics, and anti-tumor efficacy against SKOV-3 ovarian cancer were evaluated. MPEG-PLA-Lys(FB) 2 was synthesized via a three-step synthetic route, and it actively interacted with DTX in aqueous media to form stable micelles with small particle sizes (~17-19 nm) and narrow size distribution (PI PLA-Lys(FB) 2 micelles achieved delayed and sustained release manner of DTX in comparison with mPEG-PLA micelles. Further in vivo xenograft tumor model in nude mice DTX/mPEG-PLA-Lys(FB) 2 micelles demonstrated significantly higher inhibitory effect on tumor growth than the marketed formulation Taxotere. Thus, our system may hold promise as a simple and effective delivery system for DTX with a potential for translation into clinical study.

  1. Method for manufacturing carrier containing e.g. proteins for human during oral drug delivery operation for food and drug administration application in pharmaceutical industry, involves providing active ingredient to core layer

    DEFF Research Database (Denmark)

    2015-01-01

    or plastically deformable layer to increase stiction of the release layer. The method enables manufacturing the micro-container including an outer diameter of 200-500 pm and a height of 2-70 pm such that wall thickness is larger than 5 m to increase geometrical stability and reduce buckling. The method enables...... of the micro-containers containing an active ingredient or containing a core layer that is configured to accept the active ingredient such that the barrier layer partially encloses the core layer. The active ingredient is provided to the core layer when the core layer is configured to accept the active...... ingredient. USE - Method for manufacturing a multi-layered micro-container i.e. carrier, containing an active ingredient e.g. small organic molecules, proteins, peptides, vitamins, antibodies, antibody fragments, vaccines, RNA, DNA and antibiotics, for a patient e.g. human and animal, during an oral drug...

  2. Recent advances of controlled drug delivery using microfluidic platforms.

    Science.gov (United States)

    Sanjay, Sharma T; Zhou, Wan; Dou, Maowei; Tavakoli, Hamed; Ma, Lei; Xu, Feng; Li, XiuJun

    2017-09-15

    Conventional systematically-administered drugs distribute evenly throughout the body, get degraded and excreted rapidly while crossing many biological barriers, leaving minimum amounts of the drugs at pathological sites. Controlled drug delivery aims to deliver drugs to the target sites at desired rates and time, thus enhancing the drug efficacy, pharmacokinetics, and bioavailability while maintaining minimal side effects. Due to a number of unique advantages of the recent microfluidic lab-on-a-chip technology, microfluidic lab-on-a-chip has provided unprecedented opportunities for controlled drug delivery. Drugs can be efficiently delivered to the target sites at desired rates in a well-controlled manner by microfluidic platforms via integration, implantation, localization, automation, and precise control of various microdevice parameters. These features accordingly make reproducible, on-demand, and tunable drug delivery become feasible. On-demand self-tuning dynamic drug delivery systems have shown great potential for personalized drug delivery. This review presents an overview of recent advances in controlled drug delivery using microfluidic platforms. The review first briefly introduces microfabrication techniques of microfluidic platforms, followed by detailed descriptions of numerous microfluidic drug delivery systems that have significantly advanced the field of controlled drug delivery. Those microfluidic systems can be separated into four major categories, namely drug carrier-free micro-reservoir-based drug delivery systems, highly integrated carrier-free microfluidic lab-on-a-chip systems, drug carrier-integrated microfluidic systems, and microneedles. Microneedles can be further categorized into five different types, i.e. solid, porous, hollow, coated, and biodegradable microneedles, for controlled transdermal drug delivery. At the end, we discuss current limitations and future prospects of microfluidic platforms for controlled drug delivery. Copyright

  3. Classification of stimuli-responsive polymers as anticancer drug delivery systems.

    Science.gov (United States)

    Taghizadeh, Bita; Taranejoo, Shahrouz; Monemian, Seyed Ali; Salehi Moghaddam, Zoha; Daliri, Karim; Derakhshankhah, Hossein; Derakhshani, Zaynab

    2015-02-01

    Although several anticancer drugs have been introduced as chemotherapeutic agents, the effective treatment of cancer remains a challenge. Major limitations in the application of anticancer drugs include their nonspecificity, wide biodistribution, short half-life, low concentration in tumor tissue and systemic toxicity. Drug delivery to the tumor site has become feasible in recent years, and recent advances in the development of new drug delivery systems for controlled drug release in tumor tissues with reduced side effects show great promise. In this field, the use of biodegradable polymers as drug carriers has attracted the most attention. However, drug release is still difficult to control even when a polymeric drug carrier is used. The design of pharmaceutical polymers that respond to external stimuli (known as stimuli-responsive polymers) such as temperature, pH, electric or magnetic field, enzymes, ultrasound waves, etc. appears to be a successful approach. In these systems, drug release is triggered by different stimuli. The purpose of this review is to summarize different types of polymeric drug carriers and stimuli, in addition to the combination use of stimuli in order to achieve a better controlled drug release, and it discusses their potential strengths and applications. A survey of the recent literature on various stimuli-responsive drug delivery systems is also provided and perspectives on possible future developments in controlled drug release at tumor site have been discussed.

  4. Spatial Distribution of Falciparum Malaria Infections in Zanzibar: Implications for Focal Drug Administration Strategies Targeting Asymptomatic Parasite Carriers.

    Science.gov (United States)

    Björkman, Anders; Cook, Jackie; Sturrock, Hugh; Msellem, Mwinyi; Ali, Abdullah; Xu, Weiping; Molteni, Fabrizio; Gosling, Roly; Drakeley, Chris; Mårtensson, Andreas

    2017-05-01

    Optimal use of mass/targeted screen-and-treat or mass or focal drug administration as malaria elimination strategies remains unclear. We therefore studied spatial distribution of Plasmodium falciparum infections to compare simulated effects of these strategies on reducing the parasite reservoir in a pre-elimination setting. P. falciparum rapid diagnostic tests (RDTs) and molecular (polymerase chain reaction [PCR]) and serological (enzyme-linked immunosorbent assay) analyses were performed on finger-prick blood samples from a population-based survey in 3 adjacent communities. Among 5278 persons screened, 13 (0.2%) were positive by RDT and 123 (2.3%) by PCR. PCR-positive individuals were scattered over the study area, but logistic regression analysis suggested a propensity of these infections to cluster around RDT-positive individuals. The odds ratios for being PCR positive was 7.4 (95% confidence interval, 2.8-19.9) for those living in the household of an RDT-positive individual and 1.64 (1.0-2.8; P = .06) for those living within 1000 m. Treating everyone within households of RDT-positive individuals (1% population) would target 13% of those who are PCR positive. Treating all living within a radius of <300 or <1000 m (14% or 58% population) would target 30% or 66% of infections, respectively. Among 4431 serologically screened individuals, 26% were seropositive. Treating everyone within seropositive households (63% population) would target 77% of PCR-positive individuals. Presumptive malaria treatment seemed justified within RDT-positive households and potentially worth considering within, for example, a radius of <300 m. Serology was not discriminative enough in identifying ongoing infections for improving focal interventions in this setting but may rather be useful to detect larger transmission foci. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  5. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and...... membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption...

  6. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption......A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and...

  7. Grey water biodegradability.

    Science.gov (United States)

    Ghunmi, Lina Abu; Zeeman, Grietje; Fayyad, Manar; van Lier, Jules B

    2011-02-01

    Knowing the biodegradability characteristics of grey water constituents is imperative for a proper design and operation of a biological treatment system of grey water. This study characterizes the different COD fractions of dormitory grey water and investigates the effect of applying different conditions in the biodegradation test. The maximum aerobic and anaerobic biodegradability and conversion rate for the different COD fractions is determined. The results show that, on average, dormitory grey water COD fractions are 28% suspended, 32% colloidal and 40% dissolved. The studied factors incubation time, inoculum addition and temperature are influencing the determined biodegradability. The maximum biodegradability and biodegradation rate differ between different COD fractions, viz. COD(ss), COD(col) and COD(diss). The dissolved COD fraction is characterised by the lowest degradation rate, both for anaerobic and aerobic conditions. The maximum biodegradability for aerobic and anaerobic conditions is 86 and 70% respectively, whereas the first order conversion rate constant, k₂₀, is 0.119 and 0.005 day⁻¹, respectively. The anaerobic and aerobic conversion rates in relation to temperature can be described by the Arrhenius relation, with temperature coefficients of 1.069 and 1.099, respectively.

  8. Development of new ionic gelation strategy: Towards the preparation of new monodisperse and stable hyaluronic acid/β-cyclodextrin-grafted chitosan nanoparticles as drug delivery carriers for doxorubicin

    Science.gov (United States)

    Mihoub, Amina Ben; Saidat, Boubakeur; Bal, Youssef; Frochot, Céline; Vanderesse, Régis; Acherar, Samir

    2018-01-01

    In the present study, β-cyclodextrin-grafted chitosan nanoparticles (β-CD-g-CS NPs) were prepared using a new ionic gelation strategy involving a synergistic effect of NaCl (150 mmol/L), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES, 10 mmol/L), and water bath sonication. This new strategy afforded smaller and more monodisperse β-CD-g-CS NPs vs. the classical ionic gelation method. New HA/β-CD-g-CS NPs were also prepared using the above-mentioned strategy by adding hyaluronic acid (HA) to the β-CD-g-CS copolymer at different weight ratios until the ZP values conversion. The best result was obtained with the weight ratio of w(HA):w(β-CD-g-CS) = 2:1 and furnished new spherical and smooth HA/β-CD-g-CS NPs. Furthermore, the stability of β- CD-g-CS NPs and HA/β-CD-g-CS NPs at 4°C in physiological medium (pH 7.4) was compared for 3 weeks period and showed that HA/β-CD-g-CS NPs were more stable all maintaining their monodispersity and high negative ZP values compared to β-CD-g-CS NPs. Finally, preliminary study of HA/β-CD-g-CS NPs as carrier for the controlled release of the anticancer drug doxorubicin was investigated. These new HA/β-CD-g-CS NPs can potentially be used as drug delivery and targeting systems for cancer treatment.

  9. Development of new ionic gelation strategy: Towards the preparation of new monodisperse and stable hyaluronic acid/β-cyclodextrin-grafted chitosan nanoparticles as drug delivery carriers for doxorubicin

    Science.gov (United States)

    Mihoub, Amina Ben; Saidat, Boubakeur; Bal, Youssef; Frochot, Céline; Vanderesse, Régis; Acherar, Samir

    2018-03-01

    In the present study, β-cyclodextrin-grafted chitosan nanoparticles (β-CD- g-CS NPs) were prepared using a new ionic gelation strategy involving a synergistic effect of NaCl (150 mmol/L), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES, 10 mmol/L), and water bath sonication. This new strategy afforded smaller and more monodisperse β-CD- g-CS NPs vs. the classical ionic gelation method. New HA/β-CD- g-CS NPs were also prepared using the above-mentioned strategy by adding hyaluronic acid (HA) to the β-CD- g-CS copolymer at different weight ratios until the ZP values conversion. The best result was obtained with the weight ratio of w(HA): w(β-CD- g-CS) = 2:1 and furnished new spherical and smooth HA/β-CD- g-CS NPs. Furthermore, the stability of β- CD- g-CS NPs and HA/β-CD- g-CS NPs at 4°C in physiological medium (pH 7.4) was compared for 3 weeks period and showed that HA/β-CD- g-CS NPs were more stable all maintaining their monodispersity and high negative ZP values compared to β-CD- g-CS NPs. Finally, preliminary study of HA/β-CD- g-CS NPs as carrier for the controlled release of the anticancer drug doxorubicin was investigated. These new HA/β-CD- g-CS NPs can potentially be used as drug delivery and targeting systems for cancer treatment.

  10. Processing of Polymer Nanofibers Through Electrospinning as Drug Delivery Systems

    Science.gov (United States)

    Kenawy, E.; Abdel-Hay, F. I.; El-Newehy, M. H.; Wnek, G. E.

    The use of electrospun fibers as drug carriers could be promising in the future for biomedical applications, especially postoperative local chemotherapy. In this research, electrospun fibers were developed as a new system for the delivery of ketoprofen as non-steroidal anti-inflammatory drug (NSAID). The fibers were made either from polycaprolactone (PCL) as a biodegradable polymer or polyurethane (PU) as a non-biodegradable polymer, or from the blends of the two. The release of the ketoprofen was followed by UV—VIS spectroscopy in phosphate buffer of pH 7.4 at 37°C and 20°C. The results showed that the release rates from the polycaprolactone, polyurethane and their blend were similar. However, the blend of the polycaprolactone with polyurethane improved its visual mechanical properties. Release profiles from the electrospun mats were compared to cast films of the various formulations.

  11. Treating acute cystitis with biodegradable micelle-encapsulated quercetin

    Science.gov (United States)

    Wang, Bi Lan; Gao, Xiang; Men, Ke; Qiu, Jinfeng; Yang, Bowen; Gou, Ma Ling; Huang, Mei Juan; Huang, Ning; Qian, Zhi Yong; Zhao, Xia; Wei, Yu Quan

    2012-01-01

    Intravesical application of an anti-inflammatory drug is an efficient strategy for acute cystitis therapy. Quercetin (QU) is a potent anti-inflammatory agent; however, its poor water solubility restricts its clinical application. In an attempt to improve water solubility of QU, biodegradable monomethoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL) micelles were used to encapsulate QU by self-assembly methods, creating QU/MPEG-PCL micelles. These QU/MPEG-PCL micelles with DL of 7% had a mean particle size of <34 nm, and could release QU for an extended period in vitro. The in vivo study indicated that intravesical application of MPEG-PCL micelles did not induce any toxicity to the bladder, and could efficiently deliver cargo to the bladder. Moreover, the therapeutic efficiency of intravesical administration of QU/MPEG-PCL micelles on acute cystitis was evaluated in vivo. Results indicated that QU/MPEG-PCL micelle treatment efficiently reduced the edema and inflammatory cell infiltration of the bladder in an Escherichia coli-induced acute cystitis model. These data suggested that MPEG-PCL micelle was a candidate intravesical drug carrier, and QU/MPEG-PCL micelles may have potential application in acute cystitis therapy. PMID:22661886

  12. Encapsulation of proteins in hydrogel carrier systems for controlled drug delivery: influence of network structure and drug size on release rate.

    Science.gov (United States)

    Bertz, Andreas; Wöhl-Bruhn, Stefanie; Miethe, Sebastian; Tiersch, Brigitte; Koetz, Joachim; Hust, Michael; Bunjes, Heike; Menzel, Henning

    2013-01-20

    Novel hydrogels based on hydroxyethyl starch modified with polyethylene glycol methacrylate (HES-P(EG)₆MA) were developed as delivery system for the controlled release of proteins. Since the drug release behavior is supposed to be related to the pore structure of the hydrogel network the pore sizes were determined by cryo-SEM, which is a mild technique for imaging on a nanometer scale. The results showed a decreasing pore size and an increase in pore homogeneity with increasing polymer concentration. Furthermore, the mesh sizes of the hydrogels were calculated based on swelling data. Pore and mesh size were significantly different which indicates that both structures are present in the hydrogel. The resulting structural model was correlated with release data for bulk hydrogel cylinders loaded with FITC-dextran and hydrogel microspheres loaded with FITC-IgG and FITC-dextran of different molecular size. The initial release depended much on the relation between hydrodynamic diameter and pore size while the long term release of the incorporated substances was predominantly controlled by degradation of the network of the much smaller meshes. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. 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.

  14. Biodegradable Polymers and Stem Cells for Bioprinting

    Directory of Open Access Journals (Sweden)

    Meijuan Lei

    2016-04-01

    Full Text Available It is imperative to develop organ manufacturing technologies based on the high organ failure mortality and serious donor shortage problems. As an emerging and promising technology, bioprinting has attracted more and more attention with its super precision, easy reproduction, fast manipulation and advantages in many hot research areas, such as tissue engineering, organ manufacturing, and drug screening. Basically, bioprinting technology consists of inkjet bioprinting, laser-based bioprinting and extrusion-based bioprinting techniques. Biodegradable polymers and stem cells are common printing inks. In the printed constructs, biodegradable polymers are usually used as support scaffolds, while stem cells can be engaged to differentiate into different cell/tissue types. The integration of biodegradable polymers and stem cells with the bioprinting techniques has provided huge opportunities for modern science and technologies, including tissue repair, organ transplantation and energy metabolism.

  15. Biodegradable Polymers and Stem Cells for Bioprinting.

    Science.gov (United States)

    Lei, Meijuan; Wang, Xiaohong

    2016-04-29

    It is imperative to develop organ manufacturing technologies based on the high organ failure mortality and serious donor shortage problems. As an emerging and promising technology, bioprinting has attracted more and more attention with its super precision, easy reproduction, fast manipulation and advantages in many hot research areas, such as tissue engineering, organ manufacturing, and drug screening. Basically, bioprinting technology consists of inkjet bioprinting, laser-based bioprinting and extrusion-based bioprinting techniques. Biodegradable polymers and stem cells are common printing inks. In the printed constructs, biodegradable polymers are usually used as support scaffolds, while stem cells can be engaged to differentiate into different cell/tissue types. The integration of biodegradable polymers and stem cells with the bioprinting techniques has provided huge opportunities for modern science and technologies, including tissue repair, organ transplantation and energy metabolism.

  16. Electrosprayed nanoparticles for drug delivery and pharmaceutical applications

    Science.gov (United States)

    Sridhar, Radhakrishnan; Ramakrishna, Seeram

    2013-01-01

    Nanotechnology based Pharma has emerged significantly and has influenced the Pharma industry up to a considerable extent. Nanoparticles technology holds a good share of the nanotech Pharma and is significant in comparison with the other domains. Electrospraying technology answers the potential needs of nanoparticle production such as scalability, reproducibility, effective encapsulation etc. Many drugs have been electrosprayed with and without polymer carriers. Drug release characteristics are improved with the incorporation of biodegradable polymer carriers which sustain the release of encapsulated drug. Electrospraying is acknowledged as an important technique for the preparation of nanoparticles with respect to pharmaceutical applications. Herein we attempted to consolidate the reports pertaining to electrospraying and their corresponding therapeutic application area. PMID:23512013

  17. Hyaluronic acid for anticancer drug and nucleic acid delivery.

    Science.gov (United States)

    Dosio, Franco; Arpicco, Silvia; Stella, Barbara; Fattal, Elias

    2016-02-01

    Hyaluronic acid (HA) is widely used in anticancer drug delivery, since it is biocompatible, biodegradable, non-toxic, and non-immunogenic; moreover, HA receptors are overexpressed on many tumor cells. Exploiting this ligand-receptor interaction, the use of HA is now a rapidly-growing platform for targeting CD44-overexpressing cells, to improve anticancer therapies. The rationale underlying approaches, chemical strategies, and recent advances in the use of HA to design drug carriers for delivering anticancer agents, are reviewed. Comprehensive descriptions are given of HA-based drug conjugates, particulate carriers (micelles, liposomes, nanoparticles, microparticles), inorganic nanostructures, and hydrogels, with particular emphasis on reports of preclinical/clinical results. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Evaluation of the simultaneous removal of recalcitrant drugs (bezafibrate, gemfibrozil, indomethacin and sulfamethoxazole) and biodegradable organic matter from synthetic wastewater by electro-oxidation coupled with a biological system.

    Science.gov (United States)

    Rodríguez-Nava, Odín; Ramírez-Saad, Hugo; Loera, Octavio; González, Ignacio

    2016-12-01

    Pharmaceutical degradation in conventional wastewater treatment plants (WWTP) represents a challenge since municipal wastewater and hospital effluents contain pharmaceuticals in low concentrations (recalcitrant and persistent in WWTP) and biodegradable organic matter (BOM) is the main pollutant. This work shows the feasibility of coupling electro-oxidation with a biological system for the simultaneous removal of recalcitrant drugs (bezafibrate, gemfibrozil, indomethacin and sulfamethoxazole (BGIS)) and BOM from wastewater. High removal efficiencies were attained without affecting the performance of activated sludge. BGIS degradation was performed by advanced electrochemical oxidation and the activated sludge process for BOM degradation in a continuous reactor. The selected electrochemical parameters from microelectrolysis tests (1.2 L s(-1) and 1.56 mA cm(-2)) were maintained to operate a filter press laboratory reactor FM01-LC using boron-doped diamond as the anode. The low current density was chosen in order to remove drugs without decreasing BOM and chlorine concentration control, so as to avoid bulking formation in the biological process. The wastewater previously treated by FM01-LC was fed directly (without chemical modification) to the activated sludge reactor to remove 100% of BGIS and 83% of BOM; conversely, the BGIS contained in wastewater without electrochemical pre-treatment were persistent in the biological process and promoted bulking formation.

  19. Biodegradable modified Phba systems

    International Nuclear Information System (INIS)

    Aniscenko, L.; Dzenis, M.; Erkske, D.; Tupureina, V.; Savenkova, L.; Muizniece - Braslava, S.

    2004-01-01

    Compositions as well as production technology of ecologically sound biodegradable multicomponent polymer systems were developed. Our objective was to design some bio plastic based composites with required mechanical properties and biodegradability intended for use as biodegradable packaging. Significant characteristics required for food packaging such as barrier properties (water and oxygen permeability) and influence of γ-radiation on the structure and changes of main characteristics of some modified PHB matrices was evaluated. It was found that barrier properties were plasticizers chemical nature and sterilization with γ-radiation dependent and were comparable with corresponding values of typical polymeric packaging films. Low γ-radiation levels (25 kGy) can be recommended as an effective sterilization method of PHB based packaging materials. Purposely designed bio plastic packaging may provide an alternative to traditional synthetic packaging materials without reducing the comfort of the end-user due to specific qualities of PHB - biodegradability, Biocompatibility and hydrophobic nature

  20. Aircraft Carriers

    DEFF Research Database (Denmark)

    Nødskov, Kim; Kværnø, Ole

    as their purchases of aircraft carrier systems, makes it more than likely that the country is preparing such an acquisition. China has territorial disputes in the South China Sea over the Spratly Islands and is also worried about the security of its sea lines of communications, by which China transports the majority...... of its foreign trade, as well as its oil imports, upon which the country is totally dependent. China therefore has good reasons for acquiring an aircraft carrier to enable it to protect its national interests. An aircraft carrier would also be a prominent symbol of China’s future status as a great power......, then the country will also acquire the capability to project military power into the region beyond Taiwan, which it does not possess today. In this way, China will have the military capability to permit a change of strategy from the mainly defensive, mainland, Taiwan-based strategy to a more assertive strategy...

  1. Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model

    Directory of Open Access Journals (Sweden)

    Hu YL

    2011-12-01

    biodegradable materials, and may help us to understand better the nanotoxicity of drug delivery carriers.Keywords: chitosan, nanoparticles, zebrafish embryo, nanotoxicology

  2. A poly(ether-ester) copolymer for the preparation of nanocarriers with improved degradation and drug delivery kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Gagliardi, M., E-mail: mariacristina.gagliardi@iit.it [Center for Micro Bio-Robotics @SSSA, Istituto Italiano di Tecnologia, Viale Rinaldo Piaggio 34, 56025 Pontedera (Italy); Bertero, A. [Department of Biology, Unit of Cellular and Developmental Biology, University of Pisa, S.S.12 Abetone e Brennero 4, 56127 Pisa (Italy); Center for Neuroscience and Cognitive Systems @UNITN, Istituto Italiano di Tecnologia, Corso Bettini 31, 38068 Rovereto (Italy); Bardi, G. [Center for Bio-Molecular Nanotechnologies @UniLe, Istituto Italiano di Tecnologia, Via Barsanti, 73010 Arnesano (Italy); Bifone, A. [Center for Neuroscience and Cognitive Systems @UNITN, Istituto Italiano di Tecnologia, Corso Bettini 31, 38068 Rovereto (Italy)

    2016-02-01

    This paper reports the synthesis and the physicochemical, functional and biological characterisations of nanocarriers made of a novel di-block biodegradable poly(ether-ester) copolymer. This material presents tunable, fast biodegradation rates, but its products are less acidic than those of other biosorbable polymers like PLGA, thus presenting a better biocompatibility profile and the possibility to carry pH-sensitive payloads. A method for the production of monodisperse and spherical nanoparticles is proposed; drug delivery kinetics and blood protein adsorption were measured to evaluate the functional properties of these nanoparticles as drug carriers. The copolymer was labelled with a fluorescent dye for internalisation tests, and rhodamine B was used as a model cargo to study transport and release inside cultured cells. Biological tests demonstrated good cytocompatibility, significant cell internalisation and the possibility to vehiculate non-cell penetrating moieties into endothelial cells. Taken together, these results support the potential use of this nanoparticulate system for systemic administration of drugs. - Highlights: • We propose a novel biodegradable nanocarrier for intracellular drug delivery. • Biodegradation rates can be finely tuned by controlling copolymer composition. • Degradation products are less acidic, thus enabling delivery of pH-sensitive cargoes. • We demonstrate intracellular delivery of a non-cell-penetrating model drug. • No significant membrane damage by the polymer nanocarriers is observed.

  3. A poly(ether-ester) copolymer for the preparation of nanocarriers with improved degradation and drug delivery kinetics

    International Nuclear Information System (INIS)

    Gagliardi, M.; Bertero, A.; Bardi, G.; Bifone, A.

    2016-01-01

    This paper reports the synthesis and the physicochemical, functional and biological characterisations of nanocarriers made of a novel di-block biodegradable poly(ether-ester) copolymer. This material presents tunable, fast biodegradation rates, but its products are less acidic than those of other biosorbable polymers like PLGA, thus presenting a better biocompatibility profile and the possibility to carry pH-sensitive payloads. A method for the production of monodisperse and spherical nanoparticles is proposed; drug delivery kinetics and blood protein adsorption were measured to evaluate the functional properties of these nanoparticles as drug carriers. The copolymer was labelled with a fluorescent dye for internalisation tests, and rhodamine B was used as a model cargo to study transport and release inside cultured cells. Biological tests demonstrated good cytocompatibility, significant cell internalisation and the possibility to vehiculate non-cell penetrating moieties into endothelial cells. Taken together, these results support the potential use of this nanoparticulate system for systemic administration of drugs. - Highlights: • We propose a novel biodegradable nanocarrier for intracellular drug delivery. • Biodegradation rates can be finely tuned by controlling copolymer composition. • Degradation products are less acidic, thus enabling delivery of pH-sensitive cargoes. • We demonstrate intracellular delivery of a non-cell-penetrating model drug. • No significant membrane damage by the polymer nanocarriers is observed.

  4. 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

  5. Methotrexate-loaded biodegradable nanoparticles: preparation ...

    Indian Academy of Sciences (India)

    Administrator

    and treat several life-threatening diseases. Delivery of drugs through nanoparticulate-based drug carriers has attained an attractive alternative mainly, in the treatment of different types of malignancies. These sub-micronic particles have potential to target the tumour sites pa- ssively, through enhanced permeation retention ...

  6. Methotrexate-loaded biodegradable nanoparticles: preparation ...

    Indian Academy of Sciences (India)

    Administrator

    effects as well as to achieve anticipated sustained release properties. In recent years, biodegradable polymeric ... 8 h and lyophilized with vacuum pressure of < 50 mTorr and at a temperature of –40 °C for 48 h. ... out in dialysis tubing using phosphate buffer pH 6∙8 at. 37 ± 0∙5 °C and at 50 rpm. In vitro drug release was.

  7. Editorial: Biodegradable Materials

    Directory of Open Access Journals (Sweden)

    Carl Schaschke

    2014-11-01

    Full Text Available This Special Issue “Biodegradable Materials” features research and review papers concerning recent advances on the development, synthesis, testing and characterisation of biomaterials. These biomaterials, derived from natural and renewable sources, offer a potential alternative to existing non-biodegradable materials with application to the food and biomedical industries amongst many others. In this Special Issue, the work is expanded to include the combined use of fillers that can enhance the properties of biomaterials prepared as films. The future application of these biomaterials could have an impact not only at the economic level, but also for the improvement of the environment.

  8. Cellular uptake of glucoheptoamidated poly(amidoamine) PAMAM G3 dendrimer with amide-conjugated biotin, a potential carrier of anticancer drugs.

    Science.gov (United States)

    Uram, Łukasz; Szuster, Magdalena; Filipowicz, Aleksandra; Zaręba, Magdalena; Wałajtys-Rode, Elżbieta; Wołowiec, Stanisław

    2017-01-15

    In search for soluble derivatives of PAMAM dendrimers as potential carriers for hydrophobic drugs, the conjugates of PAMAM G3 with biotin, further converted into glycodendrimer with d-glucoheptono-1,4-lactone, were prepared. Polyamidoamine dendrimer (PAMAM) of third generation, G3 was functionalized with four biotin equivalents covalently attached to terminal amine nitrogens via amide bond G3 4B . The remaining 28 amine groups were blocked by glucoheptoamide substituents (gh) to give G3 4B28gh or with one fluorescein equivalent (attached by reaction of G3 4B with fluorescein isothiocyanate, FITC) via thiourea bond as FITC followed by exhaustive glucoheptoamidation to get G3 4B27gh1F . As a control the G3 substituted totally with 32 glucoheptoamide residues, G3 gh and its fluorescein labeled analogue G3 31gh1F were synthesized. The glucoheptoamidation of PAMAM G0 dendrimer with glucoheptono-1,4-lactone was performed in order to fully characterize the 1 H NMR spectra of glucoheptoamidated PAMAM dendrimers and to control the derivatization of G3 with glucoheptono-1,4-lactone. Another two derivatives of G3, namely G3 4B28gh1F' and G3 32ghF' , with ester bonded fluorescein were also obtained. Biological properties of obtained dendrimer conjugates were estimated in vitro with human cell lines: normal fibroblast (BJ) and two cancer glioblastoma (U-118 MG) and squamous carcinoma (SCC-15), including cytotoxicity by reduction of XTT and neutral red (NR) assays. Cellular uptake of dendrimer conjugates was evaluated with confocal microscopy. Obtained results confirmed, that biotinylated bioconjugates have always lower cytotoxicity and 3-4 times higher cellular uptake than non-biotinylated dendrimer conjugates in all cell lines. Comparison of various cell lines revealed different dose-dependent cell responses and the lower cytotoxicity of examined dendrimer conjugates for normal fibroblasts and squamous carcinoma, as compared with much higher cytotoxic effects seen in

  9. Synthesis and evaluation of sodium deoxycholate sulfate as a lipid drug carrier to enhance the solubility, stability and safety of an amphotericin B inhalation formulation.

    Science.gov (United States)

    Gangadhar, Katkam N; Adhikari, Kajiram; Srichana, Teerapol

    2014-08-25

    Amphotericin B (AmB) is still used as the gold standard for therapy against invasive fungal diseases. However, the use of AmB through oral administration is restricted due to its low solubility and stability in aqueous solution, which is the cause for its poor bioavailability and highly varying absorption. Therefore, an attempt has been made to enhance the solubility and stability of AmB to evaluate its bioactivity and safety for use as an inhaler by using a new excipient sodium deoxycholate sulfate (SDS) with aim of using it as a drug carrier for AmB. Therefore, SDS was formulated together with AmB as a dry powder by lyophilization. The dry powder was reconstituted in distilled water and evaluated its physicochemical properties such as zeta potential, particle size and pH to compare its solubility and stability of the formulations with a SDC-AmB (i.e., known as Fungizone(®)). In vitro toxicity studies were carried out with red blood cells (RBC) and respiratory cell lines. Bioactivity was determined by a micro-dilution method against Candidaalbicans and Cryptococcusneoformans. We found that SDS-AmB had a zeta potential (-45.53 mV), which was higher than of Fungizone(®); and produced a stable particle size in solution (73.8 nm). The particle size distributions of both formulations were expressed as their mass median aerodynamic diameters (MMAD; 1.70 and 1.74 μm), their fine particle fractions (FPF; 70 and 80%) and geometric standard deviations (GSD; 2.3 and 2.0), respectively. These values indicated that the sizes were appropriate for use in an inhaler. Pure AmB was found to hemolyse RBC and was very toxic to alveolar macrophage cells, as their viability rapidly declined from 93 to 56% when the AmB concentration increased from 1 to 8 μg/mL. The SDS-AmB formulation had a significantly reduced toxicity compared to AmB. The results clearly indicated that the SDS-lipid based nanoparticles had the potential to be used as an alternative option to Fungizone(®) for an

  10. Biodegradable polymers derived from amino acids.

    Science.gov (United States)

    Khan, Wahid; Muthupandian, Saravanan; Farah, Shady; Kumar, Neeraj; Domb, Abraham J

    2011-12-08

    In the past three decades, the use of polymeric materials has increased dramatically for biomedical applications. Many α-amino acids derived biodegradable polymers have also been intensely developed with the main goal to obtain bio-mimicking functional biomaterials. Polymers derived from α-amino acids may offer many advantages, as these polymers: (a) can be modified further to introduce new functions such as imaging, molecular targeting and drugs can be conjugated chemically to these polymers, (b) can improve on better biological properties like cell migration, adhesion and biodegradability, (c) can improve on mechanical and thermal properties and (d) their degradation products are expected to be non-toxic and readily metabolized/excreted from the body. This manuscript focuses on biodegradable polymers derived from natural amino acids, their synthesis, biocompatibility and biomedical applications. It is observed that polymers derived from α-amino acids constitute a promising family of biodegradable materials. These provide innovative multifunctional polymers possessing amino acid side groups with biological activity and with innumerous potential applications. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Biodegradable Shape Memory Polymers in Medicine.

    Science.gov (United States)

    Peterson, Gregory I; Dobrynin, Andrey V; Becker, Matthew L

    2017-11-01

    Shape memory materials have emerged as an important class of materials in medicine due to their ability to change shape in response to a specific stimulus, enabling the simplification of medical procedures, use of minimally invasive techniques, and access to new treatment modalities. Shape memory polymers, in particular, are well suited for such applications given their excellent shape memory performance, tunable materials properties, minimal toxicity, and potential for biodegradation and resorption. This review provides an overview of biodegradable shape memory polymers that have been used in medical applications. The majority of biodegradable shape memory polymers are based on thermally responsive polyesters or polymers that contain hydrolyzable ester linkages. These materials have been targeted for use in applications pertaining to embolization, drug delivery, stents, tissue engineering, and wound closure. The development of biodegradable shape memory polymers with unique properties or responsiveness to novel stimuli has the potential to facilitate the optimization and development of new medical applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Drug composition matters: the influence of carrier concentration on the radiochemical purity, hydroxyapatite affinity and in-vivo bone accumulation of the therapeutic radiopharmaceutical 188Rhenium-HEDP.

    Science.gov (United States)

    Lange, R; de Klerk, J M H; Bloemendal, H J; Ramakers, R M; Beekman, F J; van der Westerlaken, M M L; Hendrikse, N H; Ter Heine, R

    2015-05-01

    (188)Rhenium-HEDP is an effective bone-targeting therapeutic radiopharmaceutical, for treatment of osteoblastic bone metastases. It is known that the presence of carrier (non-radioactive rhenium as ammonium perrhenate) in the reaction mixture during labeling is a prerequisite for adequate bone affinity, but little is known about the optimal carrier concentration. We investigated the influence of carrier concentration in the formulation on the radiochemical purity, in-vitro hydroxyapatite affinity and the in-vivo bone accumulation of (188)Rhenium-HEDP in mice. The carrier concentration influenced hydroxyapatite binding in-vitro as well as bone accumulation in-vivo. Variation in hydroxyapatite binding with various carrier concentrations seemed to be mainly driven by variation in radiochemical purity. The in-vivo bone accumulation appeared to be more complex: satisfactory radiochemical purity and hydroxyapatite affinity did not necessarily predict acceptable bio-distribution of (188)Rhenium-HEDP. For development of new bisphosphonate-based radiopharmaceuticals for clinical use, human administration should not be performed without previous animal bio-distribution experiments. Furthermore, our clinical formulation of (188)Rhenium-HEDP, containing 10 μmol carrier, showed excellent bone accumulation that was comparable to other bisphosphonate-based radiopharmaceuticals, with no apparent uptake in other organs. Radiochemical purity and in-vitro hydroxyapatite binding are not necessarily predictive of bone accumulation of (188)Rhenium-HEDP in-vivo. The formulation for (188)Rhenium-HEDP as developed by us for clinical use exhibits excellent bone uptake and variation in carrier concentration during preparation of this radiopharmaceutical should be avoided. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Polymer nanoparticles for drug and small silencing RNA delivery to treat cancers of different phenotypes

    Science.gov (United States)

    Devulapally, Rammohan; Paulmurugan, Ramasamy

    2013-01-01

    Advances in nanotechnology have provided powerful and efficient tools in development of cancer diagnosis and therapy. There are numerous nanocarriers that are currently approved for clinical use in cancer therapy. In recent years, biodegradable polymer nanoparticles (NPs) have attracted a considerable attention for their ability to function as a possible carrier for target-specific delivery of various drugs, genes, proteins, peptides, vaccines, and other biomolecules in humans without much toxicity. This review will specifically focus on the recent advances in polymer-based nanocarriers for various drugs and small silencing RNA’s loading and delivery to treat different types of cancer. PMID:23996830

  14. Permeation measurement of gestodene for some biodegradable materials using Franz diffusion cells

    OpenAIRE

    Liu, Danhua; Zhang, Chong; Zhang, Xiaowei; Zhen, Zhu; Wang, Ping; Li, Jianxin; Yi, Dongxu; Jin, Ying; Yang, Dan

    2015-01-01

    Biodegradable poly(d,l-lactide) (PDLLA), Poly(trimethylene carbonate) (PTMC), polycaprolactone (PCL), poly(caprolactone-co-d,l-lactide) (PCDLLA) and poly(trimethylene carbonate-co-caprolactone) (PTCL) are recently used for clinical drug delivery system such as subcutaneous contraceptive implant capsule due to their biodegradable properties that they could possess long-term stable performance in vivo without removal, however their permeation rate is unknown. In the work, biodegradable material...

  15. Nanotechnology based targeted drug delivery.

    Science.gov (United States)

    Ruggiero, Carmelina; Pastorino, Laura; Herrera, Oscar L

    2010-01-01

    NANOTECHNOLOGY is having a great impact on many industrial applications, such as manufacturing, semiconductors, nanostructured materials and biotechnology. As relates to the latter, nanobiotechnology focuses on the ability to work at the molecular and atomic level to fabricate structures combining biological materials and synthetic materials, taking into account engineering, physics, chemistry, genomics and proteomics. The main goals relate to biosensors, nanosized microchips, and more generally to medical applications at the molecular level. Nanotechnology has been recently extensively applied to treatment and diagnosis of diseases and the new term nanomedicine has been introduced, for which several definitions have so far been proposed [1]-[3] which focus on the use of engineered nano-devices and nanostructures for diagnosis and treatment. One of the key aspects of nanomedicine is targeted drug delivery by nanoscale drug carriers. At present, 95 % of all new potential therapeutics have poor pharmaco kinetics and biopharmaceutical properties, there is therefore a great need to develop drug delivery [4] systems that convey the therapeutically active molecules only to the site of action, without affecting other organs and tissues [5]. This allows to lower required doses of drugs and to increase their therapeutic indices and safety profiles. It is possible to fabricate nanoparticles or nanocapsules with different properties as relates to drug encapsulation and release. A great amount of nanoscale systems for drug delivery has been investigated; they include liposomes, dendrimers, quantum dots, nanotubes, polymeric biodegradable nanoparticles and nanocapsules [6].

  16. Biodegradable Sonobuoy Decelerators

    Science.gov (United States)

    2015-06-01

    agent. Samples were also analyzed for heavy metals which found concentrations below the toxicity threshold, ruling out metals contamination during...unlimited” 13. SUPPLEMENTARY NOTES 14. ABSTRACT In response to environmental concerns regarding nylon decelerators from sonobuoys polluting the oceans...readiness point for technology transition. 15. SUBJECT TERMS biodegrade, decelerator, sonobuoy, polyvinyl alcohol, polyhydroxyalkanoate, marine

  17. Biodegradable Materials for Nonwovens

    Science.gov (United States)

    Demand for nonwovens is increasing globally, particularly in the disposable products area. As the consumption of nonwoven products with short life increases, the burden on waste disposal also rises. In this context, biodegradable nonwovens become more important today and for the future. Several new ...

  18. Microspheres prepared with biodegradable PHBV and PLA polymers as prolonged-release system for ibuprofen: in vitro drug release and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Giovana Carolina Bazzo

    2012-12-01

    Full Text Available In this study, poly(hydroxybutyrate-co-hydroxyvalerate (PHBV and poly(l-lactide (PLA microspheres containing ibuprofen were prepared with the aim of prolonging the drug release. The oil-in-water (O/W emulsion solvent evaporation technique was used, varying the polymer ratio. All formulations provided spherical particles with drug crystals on the surface and a porous and rough polymeric matrix when PHBV was used and smooth external surface when prepared with PLA. The in vitro dissolution profiles show that the formulation containing PHBV/PLA at the proportion of 30/70 presented the best results in terms of prolonging the ibuprofen release. The analysis of the concentration of ibuprofen in the blood of rats showed that maximum levels were achieved at between one and two hours after administration of the immediate-release form (pure drug, while the prolonged microspheres led to a small amount of the drug being released within the first two hours and reached the maximum level after six hours of administration. It was concluded that it is possible to prolong the release of ibuprofen through its incorporation into PHBV/PLA microspheres.No presente estudo foram preparadas microesferas de poli(hidroxibutirato-co-hidroxivalerato (PHBV e poli(ácido láctico (PLA com o objetivo de prolongar a liberação do ibuprofeno, utilizado como fármaco modelo. Empregou-se o método de emulsificação e evaporação do solvente óleo em água (O/A, variando-se a proporção entre os polímeros. Todas as formulações originaram partículas esféricas com cristais de fármaco aderidos à superfície externa. As microesferas apresentaram superfície rugosa e porosa, quando o PHBV foi utilizado, e superfície externa lisa, quando preparadas com o PLA. Os perfis de dissolução in vitro evidenciaram que a formulação que continha PHBV/PLA na proporção de 30/70 apresentou melhores resultados para prolongar a liberação do ibuprofeno. Através da análise da concentra

  19. Can a Biodegradable Implanted Bilayered Drug Delivery System Loaded with BMP-2/BMP-12 Take an Effective Role in the Biological Repair Process of Bone–Tendon Injuries? A Preliminary Report

    Directory of Open Access Journals (Sweden)

    Baran Komur

    2017-01-01

    Full Text Available Background. Use of biodegradable and biocompatible materials in the orthopedic surgery is gaining popularity. In this research, the rate of controlled release of a bilayered prototype biomaterial designed to promote osteoblastic and tenoblastic activity was calculated using pharmacochemical methods. Methods. The first part of the design, composed of a sodium tetraborate, polyvinyl alcohol, and starch based hydrogel, was loaded with bone morphogenic protein-2. The second part which was composed of a sodium tetraborate, polyvinyl alcohol, and chitosan based hydrogel was loaded with bone morphogenic protein-12. Osteochondral and tendon tissue specimens were obtained from patients with a diagnosis of gonarthrosis and primary bone cells and tendon cells cultures were prepared following treatment with collagenase enzyme. Cell samples were collected from the groups by means of an invert light microscope and environmental scanning electron microscope underwent at the 1st and 21st days. The level of osteogenic differentiation was measured by the activity of alkaline phosphatase. For the statistical evaluation of the obtained data, groups were compared with post hoc Tukey test following analysis of variance. Level of significance was accepted to be <0,01. Results. Both osteogenic and tenogenic stimulation were observed in the cultured specimens. In comparison to the control groups, the rate of proliferation of healthy cells was found to be higher in the groups to which the design was added (p<0.01. Conclusions. Our research is a preliminary report that describes a study conducted in an in vitro experimental setting. We believe that such prototype systems may be pioneers in targeted drug therapies after reconstructional surgeries.

  20. Poly(ϵ-caprolactone) microcapsules and nanocapsules in drug delivery.

    Science.gov (United States)

    Pohlmann, Adriana Raffin; Fonseca, Francisco Noe; Paese, Karina; Detoni, Cassia Britto; Coradini, Karine; Beck, Ruy Cr; Guterres, Silvia S

    2013-05-01

    Poly(ϵ-caprolactone) (PCL), a biodegradable and biocompatible polymer, is useful to encapsulate a wide range of drugs making it an interesting material for the preparation of carriers with potential applications in therapeutics. The design and development of those carriers to modulate drug release, to improve the drug stability or apparent solubility in aqueous media, as well as to target tissues and organs are discussed. Microencapsulation is a well-established process in pharmaceutical industry to protect drugs from chemical degradation and to control drug release. In this context, PCL is a useful polymer to prepare microcapsules. Nanoencapsulation, a more recent approach, offers new possibilities in drug delivery. PCL can be used as polymer to prepare different types of nanocapsules presenting diverse flexibility according to the chemical nature of the core. Those nanocapsules are capable of controlling drug release and improving photochemical stability. In addition, they can modulate cutaneous drug penetration/permeation and act as physical sunscreen due to their capability of light scattering. Considering the pharmaceutical point of view, PCL nanocapsules are versatile formulations, once they can be used in the liquid form, as well as incorporated into semi-solid or solid dosage forms.

  1. Drug composition matters : The influence of carrier concentration on the radiochemical purity, hydroxyapatite affinity and in-vivo bone accumulation of the therapeutic radiopharmaceutical 188Rhenium-HEDP

    NARCIS (Netherlands)

    Lange, R.; de Klerk, J. M H; Bloemendal, H. J.|info:eu-repo/dai/nl/269266178; Ramakers, R. M.; Beekman, F. J.|info:eu-repo/dai/nl/107730200; van der Westerlaken, M. M L; Hendrikse, N. H.; ter Heine, R.

    2015-01-01

    Introduction: 188Rhenium-HEDP is an effective bone-targeting therapeutic radiopharmaceutical, for treatment of osteoblastic bone metastases. It is known that the presence of carrier (non-radioactive rhenium as ammonium perrhenate) in the reaction mixture during labeling is a prerequisite for

  2. Drug composition matters: the influence of carrier concentration on the radiochemical purity, hydroxyapatite affinity and in-vivo bone accumulation of the therapeutic radiopharmaceutical 188Rhenium-HEDP

    NARCIS (Netherlands)

    Lange, R.; Klerk, J.M. de; Bloemendal, H.J.; Ramakers, R.M.; Beekman, F.J.; Westerlaken, M.M. van der; Hendrikse, N.H.; Heine, R. ter

    2015-01-01

    INTRODUCTION: (188)Rhenium-HEDP is an effective bone-targeting therapeutic radiopharmaceutical, for treatment of osteoblastic bone metastases. It is known that the presence of carrier (non-radioactive rhenium as ammonium perrhenate) in the reaction mixture during labeling is a prerequisite for

  3. Bacterial Carriers for Glioblastoma Therapy

    Directory of Open Access Journals (Sweden)

    Nalini Mehta

    2017-03-01

    Full Text Available Treatment of aggressive glioblastoma brain tumors is challenging, largely due to diffusion barriers preventing efficient drug dosing to tumors. To overcome these barriers, bacterial carriers that are actively motile and programmed to migrate and localize to tumor zones were designed. These carriers can induce apoptosis via hypoxia-controlled expression of a tumor suppressor protein p53 and a pro-apoptotic drug, Azurin. In a xenograft model of human glioblastoma in rats, bacterial carrier therapy conferred a significant survival benefit with 19% overall long-term survival of >100 days in treated animals relative to a median survival of 26 days in control untreated animals. Histological and proteomic analyses were performed to elucidate the safety and efficacy of these carriers, showing an absence of systemic toxicity and a restored neural environment in treated responders. In the treated non-responders, proteomic analysis revealed competing mechanisms of pro-apoptotic and drug-resistant activity. This bacterial carrier opens a versatile avenue to overcome diffusion barriers in glioblastoma by virtue of its active motility in extracellular space and can lead to tailored therapies via tumor-specific expression of tumoricidal proteins.

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

    Science.gov (United States)

    Kim, Bum-Gil; Kang, Ik-Joong

    2008-09-01

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

  5. Treating acute cystitis with biodegradable micelle-encapsulated quercetin

    Directory of Open Access Journals (Sweden)

    Wang BL

    2012-05-01

    Full Text Available Bi Lan Wang1, Xiang Gao1,2, Ke Men1, Jinfeng Qiu1, Bowen Yang3, Ma Ling Gou1, Mei Juan Huang1, Ning Huang2, Zhi Yong Qian1, Xia Zhao1, Yu Quan Wei11State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, 2Department of Pathophysiology, College of Preclinical and Forensic Medical Sciences, 3College of Life Science, Sichuan University, Chengdu, People’s Republic of ChinaAbstract: Intravesical application of an anti-inflammatory drug is an efficient strategy for acute cystitis therapy. Quercetin (QU is a potent anti-inflammatory agent; however, its poor water solubility restricts its clinical application. In an attempt to improve water solubility of QU, biodegradable monomethoxy poly(ethylene glycol-poly(ε-caprolactone (MPEG-PCL micelles were used to encapsulate QU by self-assembly methods, creating QU/MPEG-PCL micelles. These QU/MPEG-PCL micelles with DL of 7% had a mean particle size of ~34 nm, and could release QU for an extended period in vitro. The in vivo study indicated that intravesical application of MPEG-PCL micelles did not induce any toxicity to the bladder, and could efficiently deliver cargo to the bladder. Moreover, the therapeutic efficiency of intravesical administration of QU/MPEG-PCL micelles on acute cystitis was evaluated in vivo. Results indicated that QU/MPEG-PCL micelle treatment efficiently reduced the edema and inflammatory cell infiltration of the bladder in an Escherichia coli-induced acute cystitis model. These data suggested that MPEG-PCL micelle was a candidate intravesical drug carrier, and QU/MPEG-PCL micelles may have potential application in acute cystitis therapy.Keywords: nanomedicine, MPEG-PCL, self-assembly

  6. Magnetically responsive paclitaxel-loaded biodegradable nanoparticles for treatment of vascular disease: preparation, characterization and in vitro evaluation of anti-proliferative potential.

    Science.gov (United States)

    Johnson, Brandon; Toland, Brent; Chokshi, Rishi; Mochalin, Vadym; Koutzaki, Sirma; Polyak, Boris

    2010-10-01

    Long term prevention of smooth muscle cell migration and proliferation inside the lumen of coronary arteries after stent implantation remains a challenge in medicine. Vascular stents have been coated with anti-proliferative drugs such as paclitaxel and rapamycin to improve the stents' efficacy. Maintaining adequate drug concentration on coronary stents presents an obstacle which magnetic nanoparticle (MNP) drug delivery could potentially overcome. Biodegradable, super-paramagnetic nanoparticles guided by high gradient magnetic fields have been proposed as transport vehicles for re-dosing stents with anti-proliferative drugs. The current study determined the characteristics of a number of candidate MNP formulations in terms of their size, surface charge, efficiency of magnetite and drug loadings, drug release profiles as well as their anti-proliferative effect on the relevant vascular cells. MNPs containing near 30% (w/w) magnetite and 12% (w/w) paclitaxel were formulated from polylactide and poly(lactide-co-glycolide) polymers using an emulsification-solvent evaporation methodology. Drug release patterns correlated well with cell growth inhibition in cultured aortic smooth muscle cells and bovine aortic endothelial cells treated with varying MNP doses. Cell viability assays revealed MNP dose-dependent cell growth inhibition over an 8-day time span for paclitaxel-loaded formulations resulting in near 80% and 100% of cell growth arrest in cultured vascular smooth muscle cells and endothelial cells respectively, while unloaded with drug formulations showed negligible variation from the non treated cells. It is concluded, that biodegradable polymeric superparamagnetic nanoparticles loaded with a relatively high level of magnetite and drug could serve as efficient carriers in vascular stent targeting applications and potentially allow re-dosing the depleted stents, thereby prolonging the lifecycle of the implant.

  7. Vascular response to percutaneous coronary intervention with biodegradable-polymer vs. new-generation durable-polymer drug-eluting stents: a meta-analysis of optical coherence tomography imaging trials.

    Science.gov (United States)

    Cassese, Salvatore; Xhepa, Erion; Ndrepepa, Gjin; Kufner, Sebastian; Colleran, Roisin; Giacoppo, Daniele; Koppara, Tobias; Mankerious, Nader; Byrne, Robert A; Laugwitz, Karl-Ludwig; Schunkert, Heribert; Fusaro, Massimiliano; Kastrati, Adnan; Joner, Michael

    2018-01-02

    Whether biodegradable-polymer drug-eluting stents (BP-DES) induce a vascular response at follow-up more favourable than that of new-generation durable-polymer drug-eluting stents (DP-DES) remains controversial. We sought to evaluate the vascular response to percutaneous coronary intervention (PCI) with BP-DES vs. new-generation DP-DES as assessed by optical coherence tomography (OCT) imaging at follow-up. We undertook a meta-analysis of aggregate data by searching electronic scientific databases for investigations of PCI-patients receiving BP-DES vs. new-generation DP-DES and OCT imaging at follow-up. The primary outcome was neointima hyperplasia (NIH) thickness. The co-primary outcome was the incidence of lesions with uncovered struts. The main secondary outcome was the incidence of lesions with malapposed struts. Among 10 trials, a total of 544 PCI-patients were assigned to BP-DES (n = 282) or new-generation DP-DES (n = 262). Of these, 447 participants with 480 treated lesions had analysable OCT imaging at a weighted median follow-up of 7 months. Lesions treated with BP-DES vs. new-generation DP-DES showed comparable NIH thickness [weighted mean difference 95% confidence intervals (CI)  = -11.37 (-29.25, 6.52); P = 0.21]. However, thick-struts (>100 μm) BP-DES showed less NIH thickness as compared to new-generation DP-DES [-20.39 (-33.83, -6.95); P = 0.003]. BP-DES vs. new-generation DP-DES showed a higher risk for uncovered struts [odds ratio 95% CI = 3.50 (1.69-7.26); P = 0.0008] and a trend towards higher risk for malapposed struts [2.01 (0.98-4.12); P = 0.06]. In PCI-patients with available OCT imaging at follow-up, BP-DES with thicker backbones delay vascular response as compared with new-generation DP-DES. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.

  8. Adverse cardiovascular events associated with biodegradable polymer drug-eluting stents and durable polymer everolimus-eluting stents: A systematic review and meta-analysis of 10 randomized controlled trials.

    Science.gov (United States)

    Bundhun, Pravesh Kumar; Janoo, Girish; Yanamala, Chandra Mouli; Huang, Feng

    2017-07-01

    Controversies have been observed among network meta-analyses comparing biodegradable polymer drug-eluting stents (BP-DES) with durable polymer drug-eluting stents (DP-DES). We aimed to compare the adverse cardiovascular events associated with BP-DES and durable polymer everolimus-eluting stents (DP-EES) using a large number of patients obtained from randomized controlled trials (RCTs). Electronic databases were searched for randomized trials comparing BP-DES with DP-EES. Adverse cardiovascular outcomes observed between 6 months and 3 years were considered as the clinical endpoints in this analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and the pooled analyses were performed with RevMan 5.3 software. All authors had full access to the data, and they have read and agreed to the manuscript as written. Ten trials involving a total number of 13,218 patients (7451 patients treated by BP-DES and 5767 patients treated by DP-EES) were included. No significant difference was observed when analyzing mortality and myocardial infarction between BP-DES and DP-EES with OR 1.08, 95% CI 0.87-1.34, P = .47 and OR 1.04, 95% CI 0.84-1.28, P = .72 respectively. Target vessel revascularization, target lesion revascularization, major adverse cardiac events, and stroke were also not significantly different with OR 1.11, 95% CI 0.92-1.33, P = .28; OR 1.11, 95% CI 0.94-1.33, P = .22; OR 1.12, 95% CI 0.99-1.27; P = .07; and OR 1.13, 95% CI 0.69-1.84; P = .62 respectively. In addition, total stent thrombosis (ST) was similarly reported between BP-DES and DP-EES with OR 0.85, 95% CI 0.59-1.21; P = .37. However, even if BP-DES were associated with a higher rate of definite ST with OR 1.69, 95% CI 0.92-3.08, P = .09 and DP-EES were associated with a higher rate of probable ST with OR 0.67, 95% CI 0.38-1.17, P = .16, these results were not statistically significant. Between 6 months and 3 years, BP-DES were similar in terms of

  9. Biodegradation of Cyanuric Acid

    Science.gov (United States)

    Saldick, Jerome

    1974-01-01

    Cyanuric acid biodegrades readily under a wide variety of natural conditions, and particularly well in systems of either low or zero dissolved-oxygen level, such as anaerobic activated sludge and sewage, soils, muds, and muddy streams and river waters, as well as ordinary aerated activated sludge systems with typically low (1 to 3 ppm) dissolved-oxygen levels. Degradation also proceeds in 3.5% sodium chloride solution. Consequently, there are degradation pathways widely available for breaking down cyanuric acid discharged in domestic effluents. The overall degradation reaction is merely a hydrolysis; CO2 and ammonia are the initial hydrolytic breakdown products. Since no net oxidation occurs during this breakdown, biodegradation of cyanuric acid exerts no primary biological oxygen demand. However, eventual nitrification of the ammonia released will exert its usual biological oxygen demand. PMID:4451360

  10. Absorbable and biodegradable polymers

    CERN Document Server

    Shalaby, Shalaby W

    2003-01-01

    INTRODUCTION NOTES: Absorbable/Biodegradable Polymers: Technology Evolution. DEVELOPMENT AND APPLICATIONOF NEW SYSTEMS: Segmented Copolyesters with Prolonged Strength Retention Profiles. Polyaxial Crystalline Fiber-Forming Copolyester. Polyethylene Glycol-Based Copolyesters. Cyanoacrylate-Based Systems as Tissue Adhesives. Chitosan-Based Systems. Hyaluronic Acid-Based Systems. DEVELOPMENTS IN PREPARATIVE, PROCESSING, AND EVALUATION METHODS: New Approaches to the Synthesis of Crystalline. Fiber-Forming Aliphatic Copolyesters. Advances in Morphological Development to Tailor the Performance of Me

  11. Drug delivery systems in domestic animal species.

    Science.gov (United States)

    Brayden, David J; Oudot, Emilie J M; Baird, Alan W

    2010-01-01

    Delivery of biologically active agents to animals is often perceived to be the poor relation of human drug delivery. Yet this field has a long and successful history of species-specific device and formulation development, ranging from simple approaches and devices used in production animals to more sophisticated formulations and approaches for a wide range of species. While several technologies using biodegradable polymers have been successfully marketed in a range of veterinary and human products, the transfer of delivery technologies has not been similarly applied across species. This may be due to a combination of specific technical requirements for use of devices in different species, inter-species pharmacokinetic, pharmacodynamic and physiological differences, and distinct market drivers for drug classes used in companion and food-producing animals. This chapter reviews selected commercialised and research-based parenteral and non-parenteral veterinary drug delivery technologies in selected domestic species. Emphasis is also placed on the impact of endogenous drug transporters on drug distribution characteristics in different species. In vitro models used to investigate carrier-dependent transport are reviewed. Species-specific expression of transporters in several tissues can account for inter-animal or inter-species pharmacokinetic variability, lack of predictability of drug efficacy, and potential drug-drug interactions.

  12. Modeling Biodegradation of Nonylphenol

    International Nuclear Information System (INIS)

    Jahan, Kauser; Ordonez, Raul; Ramachandran, Ravi; Balzer, Shira; Stern, Michael

    2008-01-01

    Nonylphenol is the primary breakdown product of nonylphenol ethoxylates, a certain class of nonionic surfactants. Nonylphenol has been found to be toxic to aquatic organisms and has been suspected of being harmful to humans due to its xenoestrogenic properties. Although there are known releases of nonylphenol to the environment, there is a lack of data describing the extent of biodegradation. This study thus focuses on much needed information on the biodegradation kinetics of nonylphenol. Oxygen uptake, cell growth and nonylphenol removal data were collected using batch reactors in an electrolytic respirometer. Nonylphenol removal, cell growth and substrate removal rates were modeled by the Monod, Haldane, Aiba, Webb, and Yano equations. The differential equations were solved by numerical integration to simulate cell growth, substrate removal, and oxygen uptake as a function of time. All models provided similar results with the Haldane model providing the best fit. The values of the kinetic parameters and the activation energy for nonylphenol were determined. These values can be used for predicting fate and transport of nonylphenol in the environment. The validity of applying each model to the biodegradation of nonylphenol was analyzed by computing the R 2 values of each equation

  13. Development of a Predictive Model for the Stabilizer Concentration Estimation in Microreservoir Transdermal Drug Delivery Systems Using Lipophilic Pressure-Sensitive Adhesives as Matrix/Carrier.

    Science.gov (United States)

    Chenevas-Paule, Clémence; Wolff, Hans-Michael; Ashton, Mark; Schubert, Martin; Dodou, Kalliopi

    2017-05-01

    Microreservoir-type transdermal drug delivery systems (MTDDS) can prevent drug crystallization; however, no current predictive model considers the impact of drug load and hydration on their physical stability. We investigated MTDDS films containing polyvinylpyrrolidone (PVP) as polymeric drug stabilizer in lipophilic pressure-sensitive adhesive (silicone). Medicated and unmedicated silicone films with different molar N-vinylpyrrolidone:drug ratios were prepared and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, microscopy, dynamic vapor sorption (DVS), and stability testing for 4 months at different storage conditions. Homogeneously distributed drug-PVP associates were observed when nonaqueous emulsions, containing drug-PVP (inner phase) and silicone adhesive (outer phase), were dried to films. DVS data were essential to predict physical stability at different humidities. A predictive thermodynamic model was developed based on drug-polymer hydrogen-bonding interactions, using the Hoffman equation, to estimate the drug-PVP ratio needed to obtain stable MTDDS and to evaluate the impact of humidity on their physical stability. This new approach considers the impact of polymorphism on drug solubility by using easily accessible experimental data (T m and DVS) and avoids uncertainties associated with the solubility parameter approach. In conclusion, a good fit of predicted and experimental data was observed. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  14. Synthesis and characterization of MnO2/NiO nanocomposites for photocatalysis of tetracycline antibiotic and modification with guanidine for carriers of Caffeic acid phenethyl ester-an anticancer drug.

    Science.gov (United States)

    Gupta, Vinod Kumar; Fakhri, Ali; Agarwal, Shilpi; Ahmadi, Elham; Nejad, Pedram Afshar

    2017-09-01

    In the present studies, modified NiO nanoparticles and MnO 2 /NiO nanocomposites with guanidine were synthesized by anchoring method for carriers of anticancer drug "Caffeic acid phenethyl ester". The prepared nanocomposites were characterized by using Scanning Electron Microscopy, Raman and Fourier transform infrared spectroscopy, X-ray diffraction, Vibrating sample magnetometer. The results from XRD indicated that the crystalline size of NiO nanoparticles and MnO 2 /NiO nanocomposites are 12 and 15nm, respectively. Saturation magnetization (Ms) for NiO NPs and MnO 2 /NiO nanocomposites was to be 0.60, and 0.68emu/g indicating that these are superparamagnetic and ferromagnetic properties in nature. The prepared nanocomposites were evaluated as catalyst for degradation of antibiotics in photocatalysis process. Particularly, the MnO 2 /NiO composite demonstrated the higher degradation rate (89.55%) of tetracycline antibiotic under UV light irradiation than the NiO (67.80%). Drug load on and release from nanopowders was investigated by using UV-Vis spectroscopy method. Time of drug loading was 100min and the drug release in 1-10h with 20-80% drug release were found, and then, it's applicable to in-vivo drug delivery. Therefore, the NiO nanoparticles and MnO 2 /NiO nanocomposites are promising for targeted Caffeic acid phenethyl ester anticancer drug delivery applications. The anticancer drug loaded on guanidine-NiO and guanidine-MnO 2 /NiO in high concentration has an antioxidant property. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Biodegradable packaging materials : case: PLA

    OpenAIRE

    Jama, Mohamed

    2017-01-01

    The main aim of this bachelor thesis was to investigate the possibility of biodegradable packaging materials. Plastics and other non-degradable packaging materials have been used for many years and they have a negative impact on the environment since they do not degrade. Different research methods are used to get authentic results, which simplifies using biodegradable packaging materials. There were two biodegradability testing methods, which has been applied to this task:-, testing biode...

  16. Development and characterization of nano-micro structures as carrier for bioactive compounds

    DEFF Research Database (Denmark)

    Boutrup Stephansen, Karen

    New biopolymers are in high demand due to their excellent biocompatibility, biodegradability, and natural origin. In this PhD project, water soluble fish sarcoplasmic proteins (FSPs) from the North Atlantic cod (Gadus morhua) have been studied as a potential new biopolymer for development of nano-micro...... structures. Two kinds of nano-micro structures have been explored: electrospun fibers (Paper I, Paper II, and Paper III) and self-assembled nanocomplexes (NCXs) (Paper IV). FSP was observed to be highly suitable for electrospinning. The fiber morphology varied significantly with FSP concentration, from beads...... showed potential as carrier system for delivery of drugs, bioactive agents, and nutraceuticals. The dipeptide Ala-Trp, rhodamine B, or insulin was encapsulated into the fibers, and the release was studied in biorelevant media (Paper I, Paper II, and Paper III). Release of Ala-Trp was slightly decreased...

  17. Screening of the structural, topological, and electronic properties of the functionalized Graphene nanosheets as potential Tegafur anticancer drug carriers using DFT method.

    Science.gov (United States)

    Shahabi, Mahnaz; Raissi, Heidar

    2017-08-22

    In the present work, we apply comprehensive theoretical calculations in order to study Tegafur drug adsorption on the nanostructured functionalized Graphene with hydroxyl, epoxide, carbonyl, and carboxyl groups in the water environment. The physical nature of Tegafur adsorption offers advantages in terms of easy desorption of anticancer molecule with no structural or electronic change of the adsorbed drug. By functionalization of Graphene nanosheet with a carbonyl group, a considerable increase on the binding energy between Tegafur drug and the nanosheet is noted. Diminish in energy gap with the adsorption of Tegafur drug on the functionalized nanosheets shows that the reactivity of functionalized complexes increases upon loading of the drug molecule. Besides, the adsorption process yields an increase of the polarity which causes the possibility of the solubility and dispersion of the considered complexes enhances. This result is indicative the suitability of the nanomaterials toward Tegafur drug delivery within the biological environments. The high solvation energy of Tegafur anticancer drug adsorbed functionalized Graphene models enforced their applicability as nanocarriers in the living system. These results are extremely relevant that the chemical modification of Graphene nanosheet using covalent functionalization scheme is an effectual approach for loading and delivery of Tegafur drug molecule within biological systems.

  18. A model for simultaneous crystallisation and biodegradation of biodegradable polymers.

    Science.gov (United States)

    Han, Xiaoxiao; Pan, Jingzhe

    2009-01-01

    This paper completes the model of biodegradation for biodegradable polymers that was previously developed by Wang et al. (Wang Y, Pan J, Han X, Sinka, Ding L. A phenomenological model for the degradation of biodegradable polymers. Biomaterials 2008;29:3393-401). Crystallisation during biodegradation was not considered in the previous work which is the topic of the current paper. For many commonly used biodegradable polymers, there is a strong interplay between crystallisation and hydrolysis reaction during biodegradation - the chain cleavage caused by the hydrolysis reaction provides an extra mobility for the polymer chains to crystallise and the resulting crystalline phase becomes more resistant to further hydrolysis reaction. This paper presents a complete theory to describe this interplay. The fundamental equations in the Avrami's theory for crystallisation are modified and coupled to the diffusion-reaction equations that were developed in our previous work. The mathematical equations are then applied to three biodegradable polymers for which long term degradation data are available in the literature. It is shown that the model can capture the behavior of the major biodegradable polymers very well.

  19. Drug release from core-shell PVA/silk fibroin nanoparticles fabricated by one-step electrospraying.

    Science.gov (United States)

    Cao, Yang; Liu, Fengqiu; Chen, Yuli; Yu, Tao; Lou, Deshuai; Guo, Yuan; Li, Pan; Wang, Zhigang; Ran, Haitao

    2017-09-20

    Silk fibroin (SF), a FDA-approved natural protein, is renowned for its great biocompatibility, biodegradability, and mechanical properties. SF-based nanoparticles provide new options for drug delivery with their tunable drug loading and release properties. To take advantage of the features of carrier polymers, we present a one-step electrospraying method that combines SF, polyvinyl alcohol (PVA) and therapeutic drugs without an emulsion process. A distinct core-shell structure was obtained with the PVA core and silk shell after the system was properly set up. The model drug, doxorubicin, was encapsulated in the core with a greater than 90% drug encapsulation efficiency. Controllable drug release profiles were achieved by alternating the PVA/SF ratio. Although the initial burst release of the drug was minimized by the SF coating, a large number of drug molecules remained entrapped by the carrier polymers. To promote and trigger drug release on demand, low intensity focused ultrasound (US) was applied. The US was especially advantageous for accelerating the drug diffusion and release. The apoptotic activity of MDA-MB-231 cells incubated with drug-loaded nanoparticles was found to increase with time. In addition, we also observed PVA/SF nanoparticles that could elicit a drug release in response to pH.

  20. [Biodegradable catheters and urinary stents. When?

    Science.gov (United States)

    Soria, F; Morcillo, E; López de Alda, A; Pastor, T; Sánchez-Margallo, F M

    2016-10-01

    One of the main wishes in the field of urinary catheters and stents is to arm them with biodegradable characteristics because we consider a failure of these devices the need for retrieval, the forgotten catheter syndrome as well as the adverse effects permanent devices cause after fulfilling their aim. The efforts focused in new designs, coatings and biomaterials aim to increase the biocompatibility of theses internal devices. Lately, there have been correct advances to answer the main challenges regarding biodegradable ureteral devices. Thus, modulation of the rate of degradation has been achieved thanks to new biomaterials and the use of copolymers that enable to choose the time of permanence as it is programmed with conventional double J catheters. Biocompatibility has improved with the use of new polymers that adapt better to the urine. Finally, one of the main problems is elimination of degraded fragments and experimentally it has be demonstrated that new designs elicit controlled degradation, from distal to proximal; using stranding and combination of copolymers degradation may be caused by dilution, reducing fragmentation to the last stages of life of the prosthesis. Moreover, it has been demonstrated that biodegradable catheters potentially may cause less urinary tract infection, less encrustation and predictably they will diminish catheter morbidity, since their degradation process reduces adverse effects. Regarding the development of biodegradable urethral stents, it is necessary to find biomaterials that enable maintaining their biomechanical properties in the long term, keeping open the urethral lumen both in patients with BPH and urethral stenosis. Modulation of the time of degradation of the prosthesis has been achieved, but the appearance of urothelial hyperplasia is still a constant in the initial phases after implantation. The development of drug eluting stents, anti-proliferative or anti-inflammatory, as well as biodegradable stents biocoated is a

  1. Size-controlled synthesis of biodegradable nanocarriers for targeted ...

    Indian Academy of Sciences (India)

    1, February 2016, pp. 69–77. c Indian Academy of Sciences. Size-controlled synthesis of biodegradable nanocarriers for targeted and controlled cancer drug delivery using salting out cation. MADASAMY HARI BALAKRISHANAN and MARIAPPAN RAJAN∗. Department of Natural Products Chemistry, School of Chemistry, ...

  2. PREPARATION AND CHARACTERIZATION OF BIODEGRADABLE ...

    African Journals Online (AJOL)

    Dr Abdusalam

    Keywords: Starch, Acetylation, Biodegradation, Poly(vinyl alcohol), Polymer blend. INTRODUCTION. Non-biodegradable polymers, such as polyethene, polypropane, poly(vinylchloride) etc have excellent mechanical properties such as tensile strength, tensile strain, bursting strength and tear strength (Hay and. Sharma.

  3. Thermodynamic Analysis of Biodegradation Pathways

    Science.gov (United States)

    Finley, Stacey D.; Broadbelt, Linda J.

    2014-01-01

    Microorganisms provide a wealth of biodegradative potential in the reduction and elimination of xenobiotic compounds in the environment. One useful metric to evaluate potential biodegradation pathways is thermodynamic feasibility. However, experimental data for the thermodynamic properties of xenobiotics is scarce. The present work uses a group contribution method to study the thermodynamic properties of the University of Minnesota Biocatalysis/Biodegradation Database. The Gibbs free energies of formation and reaction are estimated for 914 compounds (81%) and 902 reactions (75%), respectively, in the database. The reactions are classified based on the minimum and maximum Gibbs free energy values, which accounts for uncertainty in the free energy estimates and a feasible concentration range relevant to biodegradation. Using the free energy estimates, the cumulative free energy change of 89 biodegradation pathways (51%) in the database could be estimated. A comparison of the likelihood of the biotransformation rules in the Pathway Prediction System and their thermodynamic feasibility was then carried out. This analysis revealed that when evaluating the feasibility of biodegradation pathways, it is important to consider the thermodynamic topology of the reactions in the context of the complete pathway. Group contribution is shown to be a viable tool for estimating, a priori, the thermodynamic feasibility and the relative likelihood of alternative biodegradation reactions. This work offers a useful tool to a broad range of researchers interested in estimating the feasibility of the reactions in existing or novel biodegradation pathways. PMID:19288443

  4. Montmorillonite-lipid hybrid carriers for ionizable and neutral poorly water-soluble drugs: Formulation, characterization and in vitro lipolysis studies.

    Science.gov (United States)

    Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

    2017-06-30

    Lipid-based formulations (LBFs) are a popular strategy for enhancing the gastrointestinal solubilization and absorption of poorly water-soluble drugs. In light of this, montmorillonite-lipid hybrid (MLH) particles, composed of medium-chain triglycerides, lecithin and montmorillonite clay platelets, have been developed as a novel solid-state LBF. Owing to the unique charge properties of montmorillonite, whereby the clay platelet surfaces carry a permanent negative charge and the platelet edges carry a pH-dependent charge, three model poorly water-soluble drugs with different charge properties; blonanserin (weak base, pKa 7.7), ibuprofen (weak acid, pKa 4.5) and fenofibrate (neutral), were formulated as MLH particles and their performance during biorelevant in vitro lipolysis at pH 7.5 was investigated. For blonanserin, drug solubilization during in vitro lipolysis was significantly reduced 3.4-fold and 3.2-fold for MLH particles in comparison to a control lipid solution and silica-lipid hybrid (SLH) particles, respectively. It was hypothesized that strong electrostatic interactions between the anionic montmorillonite platelet surfaces and cationic blonanserin molecules were responsible for the inferior performance of MLH particles. In contrast, no significant influence on drug solubilization was observed for ibuprofen- and fenofibrate-loaded MLH particles. The results of the current study indicate that whilst MLH particles are a promising novel formulation strategy for poorly water-soluble drugs, drug ionization tendency and the potential for drug-clay interactions must be taken into consideration to ensure an appropriate performance. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Synthesis and characterization of biodegradable lignin nanoparticles with tunable surface properties

    NARCIS (Netherlands)

    Richter, Alexander P.; Bharti, Bhuvnesh; Armstrong, Hinton B.; Brown, Joseph S.; Plemmons, Dayne; Paunov, Vesselin N.; Stoyanov, Simeon D.; Velev, Orlin D.

    2016-01-01

    Lignin nanoparticles can serve as biodegradable carriers of biocidal actives with minimal environmental footprint. Here we describe the colloidal synthesis and interfacial design of nanoparticles with tunable surface properties using two different lignin precursors, Kraft (Indulin AT) lignin and

  6. Highly versatile nanohydrogel platform based on riboflavin-polysaccharide derivatives useful in the development of intrinsically fluorescent and cytocompatible drug carriers.

    Science.gov (United States)

    Di Meo, Chiara; Montanari, Elita; Manzi, Lucio; Villani, Claudio; Coviello, Tommasina; Matricardi, Pietro

    2015-01-22

    In this work we describe a new nanohydrogel platform, based on polysaccharides modified with the hydrophobic and fluorescent molecule riboflavin tetrabutyrate, which leads to innovative structures useful for drug delivery applications. Hyaluronic acid and pullulan were chosen as representative of anionic and neutral polysaccharides, respectively, and the bromohexyl derivative of riboflavin tetrabutyrate was chemically linked to these polymer chains. Because of such derivatization, polymer chains were able to self-assemble in aqueous environment thus forming nanohydrogels, with mean diameters of about 312 and 210 nm, for hyaluronan and pullulan, respectively. These new nanohydrogels showed low polydispersity index, and negative ζ-potential. Moreover, the nanohydrogels, which can be easily loaded with model drugs, showed long-term stability in water and physiological conditions and excellent cytocompatibility. All these properties allow to consider these intrinsically fluorescent nanohydrogels suitable for the formulation of innovative drug dosage forms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Designing Drug Conjugates Based on Sugar Decorated V-Shape and Star Polymethacrylates: Influence of Composition and Architecture of Polymeric Carrier.

    Science.gov (United States)

    Mielańczyk, Anna; Neugebauer, Dorota

    2015-12-16

    Amphiphilic ethylenediamine (EDA)-functionalized V-shape and star copolymers with centrally placed methyl-α,D-glucopyranoside were designed as nanocarriers. Anticancer doxorubicin (DOX) was conjugated in water via amine groups in copolymers to form ketimine linkers. Variations of arm length and number (40-65 units per arm and 2 vs 3 vs 4 arms), DOX feed amount, and conjugation site content (50-160 units of EDA groups), as responsible for efficiency of drug attachment (10-60 units of conjugated DOX) and its release at various pH (5.0 vs 7.4), were studied to demonstrate potential for drug delivery. Size of conjugate particles (10-195 nm) formed in aqueous solution was strongly dependent on the polymer composition and topology. The broad range of drug amounts (25-95%) were detected by the precipitation method, showing pH sensitivity by some polymeric conjugates with faster DOX release in acidic conditions.

  8. Preparation of Controlled-Release Particles Based on Spherical Porous Silica Used as the Drug Carrier by the Dry Coating Method.

    Science.gov (United States)

    Nakamura, Shohei; Kondo, Shihoko; Mohri, Ayaka; Sakamoto, Takatoshi; Yuasa, Hiroshi

    2018-02-12

    A controlled-release formulation is a dosage form that could improve a patient's quality of life by reducing the frequency of administration, while ensuring the continued effect of the medicine and reducing the side effects. To prepare these controlled-release particles, a wet coating method in which a drug is coated with a controlled-release material using water or an organic solvent is used, but with this method, the coating process is very time-consuming and requires large amounts of energy for the drying phase. In addition, contact with water or an organic solvent may cause problems such as alteration of the drug. Therefore, the use of a dry coating method has attracted attention as a means of overcoming these issues. However, since the drug is fixed to the surface of a core particle, it is necessary to further coat it with a water-soluble material. We used spherical porous silica (SPS) particles, considering that the drug fixation via a water-soluble material would not be necessary if the drug were to be placed in the pores of these particles. We used SPS filled with theophylline (TP), a model drug, as the core particles. To prepare controlled-release particles (CRP), a controlled-release layer consisting of hydrogenated castor oil (HCO) was applied to the core particle surface by a dry coating method. The paddle method using 1% w/v polysorbate 80 solution as the test medium was employed to estimate the TP dissolution rate of the resulting CRPs. The 50% dissolution time of TP extended from 14 to 405 min with increasing the amount of the coated HCO. The Korsmeyer-Peppas model applied to the TP dissolution behavior yielded an n value of around 1. Moreover, the K value was comparable with the case in which a zero-order model was applied. It is thought that the dissolution of TP from CRPs will conform to the zero-order model.

  9. Biodegradation of Polypropylene Nonwovens

    Science.gov (United States)

    Keene, Brandi Nechelle

    The primary aim of the current research is to document the biodegradation of polypropylene nonwovens and filament under composting environments. To accelerate the biodegradat ion, pre-treatments and additives were incorporated into polypropylene filaments and nonwovens. The initial phase (Chapter 2) of the project studied the biodegradation of untreated polypropylene with/without pro-oxidants in two types of composting systems. Normal composting, which involved incubation of samples in food waste, had little effect on the mechanical properties of additive-free spunbond nonwovens in to comparison prooxidant containing spunbond nonwovens which were affected significantly. Modified composting which includes the burial of samples with food and compressed air, the polypropylene spunbond nonwovens with/without pro-oxidants displayed an extreme loss in mechanical properties and cracking on the surface cracking. Because the untreated spunbond nonwovens did not completely decompose, the next phase of the project examined the pre-treatment of gamma-irradiation or thermal aging prior to composting. After exposure to gamma-irradiation and thermal aging, polypropylene is subjected to oxidative degradation in the presence of air and during storage after irradiat ion. Similar to photo-oxidation, the mechanism of gamma radiation and thermal oxidative degradation is fundamentally free radical in nature. In Chapter 3, the compostability of thermal aged spunbond polypropylene nonwovens with/without pro-oxidant additives. The FTIR spectrum confirmed oxidat ion of the polypropylene nonwovens with/without additives. Cracking on both the pro-oxidant and control spunbond nonwovens was showed by SEM imaging. Spunbond polypropylene nonwovens with/without pro-oxidants were also preirradiated by gamma rays followed by composting. Nonwovens with/without pro-oxidants were severely degraded by gamma-irradiation after up to 20 kGy exposure as explained in Chapter 4. Furthermore (Chapter 5), gamma

  10. Biodegradable poly lactone-family polymer and their applications in medical field

    International Nuclear Information System (INIS)

    Wang, S.; Bei, J.

    2005-01-01

    Poly lactone-family polymers such as poly lactide, poly glycolide and polycaprolactone are kind aliphatic polyester. Since they can degrade by hydrolysis reaction under all the ph condition and possess biocompatibility, biodegradability and other good properties, especially they included not peptide bond in their molecules, they are non-antigen and non-immunization, as well as have no-toxicity and no-stimulation. So they are interested biomaterials and very useful in medical field. However the properties of all of the homo-poly lactones can not be changed in a large range, the limited properties result in limited applications of these homo-poly lactones. Based on macromolecular design, a series of copolylactones such as poly(lactide-co-glycolide) (PLGA), poly(glycolide-co-lactide-co-caprolactone) tri- component copolymer (PGLC), tri- and multi-block poly lactide/poly(ethylene oxide) copolymer (TPLE and BPLE), as well as polycaprolactone/poly lactide/poly(ethylene oxide) copolymer (PCEL) et al were synthesized by copolymerization among various lactone monomers or lactone monomers with poly(ethylene glycol). These copolylactones have wide range of degradation life from several months to years and different mechanical properties. After plasma treatment the surface property of the copolylactones were improved further and cell affinity of the copolylactones was improved obviously. The applications of these poly lactone-family polymers in medical field for used as drug carrier in drug delivery system, and as cell scaffold in tissue engineering were discussed

  11. Magnetic/NIR-responsive drug carrier, multicolor cell imaging, and enhanced photothermal therapy of gold capped magnetite-fluorescent carbon hybrid nanoparticles.

    Science.gov (United States)

    Wang, Hui; Cao, Guixin; Gai, Zheng; Hong, Kunlun; Banerjee, Probal; Zhou, Shuiqin

    2015-05-07

    This paper reports a type of multifunctional hybrid nanoparticle (NP) composed of gold nanocrystals coated on and/or embedded in a magnetite-fluorescent porous carbon core-shell NP template (Fe3O4@PC-CDs-Au) for biomedical applications, including magnetic/NIR-responsive drug release, multicolor cell imaging, and enhanced photothermal therapy. The synthesis of the Fe3O4@PC-CDs-Au NPs firstly involves the preparation of core-shell template NPs with magnetite nanocrystals clustered in the cores and fluorescent carbon dots (CDs) embedded in a porous carbon shell, followed by an in situ reduction of silver ions (Ag(+)) loaded in the porous carbon shell and a subsequent replacement of Ag NPs with Au NPs through a galvanic replacement reaction using HAuCl4 as a precursor. The Fe3O4@PC-CDs-Au NPs can enter the intracellular region and light up mouse melanoma B16F10 cells in multicolor mode. The porous carbon shell, anchored with hydrophilic hydroxyl/carboxyl groups, endows the Fe3O4@PC-CDs-Au NPs with excellent stability in the aqueous phase and a high loading capacity (719 mg g(-1)) for the anti-cancer drug doxorubicin (DOX). The superparamagnetic Fe3O4@PC-CDs-Au NPs with a saturation magnetization of 23.26 emu g(-1) produce localized heat under an alternating magnetic field, which triggers the release of the loaded drug. The combined photothermal effects of the Au nanocrystals and the CDs on/in the carbon shell can not only regulate the release rate of the loaded drug, but also efficiently kill tumor cells under NIR irradiation. Benefitting from their excellent optical properties, their magnetic field and NIR light-responsive drug release capabilities and their enhanced photothermal effect, such nanostructured Fe3O4@PC-CDs-Au hybrid NPs are very promising for simultaneous imaging diagnostics and high efficacy therapy.

  12. Biodegradable Alginate-Chitosan Hollow Nanospheres for Codelivery of Doxorubicin and Paclitaxel for the Effect of Human Lung Cancer A549 Cells

    Directory of Open Access Journals (Sweden)

    Liu Tao

    2018-01-01

    Full Text Available A biodegradable alginate coated chitosan hollow nanosphere (ACHN was prepared by a hard template method and used for codelivery of doxorubicin (DOX and paclitaxel (PTX to investigate the effect on human lung cancer A549 cells. PTX was loaded into the nanometer hollow structure of ACHN through adsorption method. DOX was coated on surface of ACHN through electrostatic interaction. Drug release studies exhibited a sustained-release effect. According to X-ray diffraction patterns (XRD, differential scanning calorimetry (DSC, and Fourier transform infrared spectroscopy (FT-IR analysis, DOX structure in the loading samples (DOX-PTX-ACHN was of amorphous state while PTX was microcrystalline. Cytotoxicity experiments showed ACHN was nontoxic as carrier material and the combination of DOX and PTX in DOX-PTX-ACHN exhibited a good inhibiting effect on cell proliferation. Cell uptake experiments demonstrated that DOX-PTX-ACHN accumulated in the cytoplasm. Degradation experiments illustrated that ACHN was a biodegradable material. In summary, these results clearly indicate that ACHN can be utilized as a potential biomaterial to transport multiple drugs to be used in combination therapy.

  13. Synthesis and membrane behavior of a new class of unnatural phospholipid analogs useful as phospholipase A2 degradable liposomal drug carriers

    DEFF Research Database (Denmark)

    Andresen, Thomas Lars; Jørgensen, Kent

    2005-01-01

    A new and unnatural type of lipid analogs with the phosphocholine and phosphoglycerol head groups linked to the C-2 position of the glycerol moiety have been synthesized and the thermodynamic lipid membrane behavior has been investigated using differential scanning calorimetry. From the heat capa...... results also suggest new approaches to rationally design liposomal drug carries that can undergo a triggered activation in diseased tissue by overexpressed PLA2....

  14. A new cell line-based coculture model of the human air-blood barrier to evaluate the interaction with aerosolized drug carriers

    OpenAIRE

    Kletting, Stephanie

    2016-01-01

    Besides reducing animal testing, in vitro models allow for the pre-screening of new drug candidates in terms of safety and efficacy before they enter clinical trials. To date, models mimicking the deep lung show limitations such as cellular origin or lack of appropriate barrier properties. Therefore, the focus of this work was on the establishment of a robust and reproducible cell line-based coculture model that reflects the two major barrier structures present in the alveolar region, namely ...

  15. Electrospun Nanofibers of Guar Galactomannan for Targeted Drug Delivery

    Science.gov (United States)

    Chu, Hsiao Mei Annie

    2011-12-01

    Guar galactomannan is a biodegradable polysaccharide used widely in the food industry but also in the cosmetics, pharmaceutical, oil drilling, textile and paper industries. Guar consists of a mannose backbone and galactose side groups that are both susceptible to enzyme degradation, a unique property that can be explored for targeted drug delivery especially since those enzymes are naturally secreted by the microflora in human colon. The present study can be divided into three parts. In the first part, we discuss ways to modify guar to produce nanofibers by electrospinning, a process that involves the application of an electric field to a polymer solution or melt to facilitate production of fibers in the sub-micron range. Nanofibers are currently being explored as the next generation of drug carriers due to its many advantages, none more important than the fact that nanofibers are on a size scale that is a fraction of a hair's width and have large surface-to-volume ratio. The incorporation and controlled release of nano-sized drugs is one way in which nanofibers are being utilized in drug delivery. In the second part of the study, we explore various methods to crosslink guar nanofibers as a means to promote water-resistance in a potential drug carrier. The scope and utility of water-resistant guar nanofibers can only be fully appreciated when subsequent drug release studies are carried out. To that end, the third part of our study focuses on understanding the kinetics and diffusion mechanisms of a model drug, Rhodamine B, through moderately-swelling (crosslinked) hydrogel nanofibers in comparison to rapidly-swelling (non-crosslinked) nanofibers. Along the way, our investigations led us to a novel electrospinning set-up that has a unique collector designed to capture aligned nanofibers. These aligned nanofiber bundles can then be twisted to hold them together like yarn. From a practical standpoint, these yarns are advantageous because they come freely suspended and

  16. Amphiphilic poly{[α-maleic anhydride-ω-methoxypoly(ethylene glycol]-co-(ethyl cyanoacrylate} graft copolymer nanoparticles as carriers for transdermal drug delivery

    Directory of Open Access Journals (Sweden)

    Jinfeng Xing

    2009-10-01

    Full Text Available Jinfeng Xing, Liandong Deng, Jun Li, Anjie DongDepartment of Polymer Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, People’s Republic of ChinaAbstract: In this study, the transdermal drug delivery properties of D,L-tetrahydropalmatine (THP-loaded amphiphilic poly{[α-maleic anhydride-ω-methoxy-poly(ethylene glycol]-co-(ethyl cyanoacrylate} (PEGECA graft copolymer nanoparticles (PEGECAT NPs were evaluated by skin penetration experiments in vitro. The transdermal permeation experiments in vitro were carried out in Franz diffusion cells using THP-loaded PEGECAT NPs as the donor system. Transmission electron microscopy and Fourier transform infrared spectroscopy were used to characterize the receptor fluid. The results indicate that the THP-loaded PEGECAT NPs are able to penetrate the rat skin. Fluorescent microscopy measurements demonstrate that THP-loaded PEGECAT NPs can penetrate the skin not only via appendage routes but also via epidermal routes. This nanotechnology has potential application in transdermal drug delivery. Keywords: poly{[α-maleic anhydride-ω-methoxy-poly(ethylene glycol]-co-(ethyl cyanoacrylate}, nanoparticles, transdermal drug delivery, D,L-tetrahydropalmatine

  17. Synthesis and characterization of basil seed mucilage coated Fe3O4magnetic nanoparticles as a drug carrier for the controlled delivery of cephalexin.

    Science.gov (United States)

    Rayegan, Ali; Allafchian, Alireza; Abdolhosseini Sarsari, Ismaeil; Kameli, Parviz

    2018-02-23

    A novel drug delivery system, loaded the drug cephalexin on the basil seed mucilage coated magnetic nanoparticles (Fe 3 O 4 @BSM-CPX) was prepared and characterized by means of X-ray diffraction (XRD), Furier Transform Infrared (FTIR), Field Emission Scanning Electron Microscope (FESEM), Vibrating Sample Magnetometer (VSM), Transmission Electron Microscopy (TEM), and Anti-bacterial, and Specific Surface (BET). By comparing the size of the uncoated nanoparticles (12nm) and the size of the coated magnetite nanoparticles (6nm), it was found that with the mucilage coating being put on the magnetite nanoparticles, the size of the nanoparticle cores has also decreased. The optimum pH results showed that the higher adsorption capacity occurs when cephalexin is cationic at pH2.5 because the NH 3 + group of cephalexin interacts better with negative functional groups of the basil seed mucilage. Disk Diffusion Anti-Bacterial test showed that the loading of CPX on the Fe 3 O 4 @BSM nanocarrier, not only does not have any negative effects on the structure and performance of the drug, but also increases the antibacterial properties of CPX. Furthermore, the in vitro release of Fe 3 O 4 @BSM-CPX nanocomposites showed an initial burst release in the first 18h, followed by a more gradual and sustained release for 120h. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Penetration enhancer-containing vesicles (PEVs) as carriers for cutaneous delivery of minoxidil: in vitro evaluation of drug permeation by infrared spectroscopy.

    Science.gov (United States)

    Mura, Simona; Manconi, Maria; Fadda, Anna Maria; Sala, Maria Chiara; Perricci, Jacopo; Pini, Elena; Sinico, Chiara

    2013-01-01

    Recently, we carried out a research on new liposomal systems prepared by using in their composition a few penetration enhancers which differ for chemical structure and physicochemical properties. The penetration enhancer-containing vesicles (PEVs) were prepared by using soy lecithin and different amounts of three penetration enhancers, 2-(2-ethoxyethoxy) ethanol (Transcutol(®)), capryl-caproyl macrogol 8-glyceride (Labrasol(®)), and cineole.To study the influence of the PEVs on (trans)dermal delivery of minoxidil, in vitro diffusion experiments were performed through new born pig skin and the results were compared with that obtained applying the vesicular system without enhancer (control) after pretreatment of the skin with the various enhancers. In this study, Fourier transform infrared spectroscopy (FTIR), attenuated total reflectance FTIR (ATR-FTIR) and FTIR imaging were used to evaluate the effective penetration of minoxidil in the skin layers and to discover the influence of the enhancer on the drug topical delivery. These analytical studies allowed us to characterize the drug formulations and to evaluate the vesicle distribution into the skin. Recorded spectra confirmed that the vesicle formulations with penetration enhancers promoted drug deposition into the skin.

  19. A Review on Recent Advances in Stabilizing Peptides/Proteins upon Fabrication in Hydrogels from Biodegradable Polymers

    Directory of Open Access Journals (Sweden)

    Faisal Raza

    2018-01-01

    Full Text Available Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to overcome the shortcomings of old conventional dosage forms for small drugs (NSAIDS and large peptides and proteins. The aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All these dynamic properties of hydrogels have increased the interest in their use as a carrier for peptides and proteins to be released slowly in a sustained manner. Peptide and proteins are remarkable therapeutic agents in today’s world that allow the treatment of severe, chronic and life-threatening diseases, such as diabetes, rheumatoid arthritis, hepatitis. Despite few limitations, hydrogels provide fine tuning of proteins and peptides delivery with enormous impact in clinical medicine. Novels drug delivery systems composed of smart peptides and molecules have the ability to drive self-assembly and form hydrogels at physiological pH. These hydrogels are significantly important for biological and medical fields. The primary objective of this article is to review current issues concerned with the therapeutic peptides and proteins and impact of remarkable properties of hydrogels on these therapeutic agents. Different routes for pharmaceutical peptides and proteins and superiority over other drugs candidates are presented. Recent advances based on various approaches like self-assembly of peptides and small molecules to form novel hydrogels are also discussed. The article will also review the literature concerning the classification of hydrogels on a different basis, polymers used, “release mechanisms” their physical and chemical characteristics and diverse applications.

  20. A Review on Recent Advances in Stabilizing Peptides/Proteins upon Fabrication in Hydrogels from Biodegradable Polymers.

    Science.gov (United States)

    Raza, Faisal; Zafar, Hajra; Zhu, Ying; Ren, Yuan; -Ullah, Aftab; Khan, Asif Ullah; He, Xinyi; Han, Han; Aquib, Md; Boakye-Yiadom, Kofi Oti; Ge, Liang

    2018-01-18

    Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to overcome the shortcomings of old conventional dosage forms for small drugs (NSAIDS) and large peptides and proteins. The aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All these dynamic properties of hydrogels have increased the interest in their use as a carrier for peptides and proteins to be released slowly in a sustained manner. Peptide and proteins are remarkable therapeutic agents in today's world that allow the treatment of severe, chronic and life-threatening diseases, such as diabetes, rheumatoid arthritis, hepatitis. Despite few limitations, hydrogels provide fine tuning of proteins and peptides delivery with enormous impact in clinical medicine. Novels drug delivery systems composed of smart peptides and molecules have the ability to drive self-assembly and form hydrogels at physiological pH. These hydrogels are significantly important for biological and medical fields. The primary objective of this article is to review current issues concerned with the therapeutic peptides and proteins and impact of remarkable properties of hydrogels on these therapeutic agents. Different routes for pharmaceutical peptides and proteins and superiority over other drugs candidates are presented. Recent advances based on various approaches like self-assembly of peptides and small molecules to form novel hydrogels are also discussed. The article will also review the literature concerning the classification of hydrogels on a different basis, polymers used, "release mechanisms" their physical and chemical characteristics and diverse applications.

  1. Drug Release Mechanism of Slightly Soluble Drug from ...

    African Journals Online (AJOL)

    theophylline) from nanocomposite of zeolite (ZLT) or hydrotalcite (HTC) used as drug carrier. Methods: Nanocomposite was prepared with dispersion of either ZLT or HTC as drug carrier and theophylline (THP) as drug in drug to clay ratios of 1:2 ...

  2. Biodegradation of gallotannins and ellagitannins.

    Science.gov (United States)

    Li, Mingshu; Kai, Yao; Qiang, He; Dongying, Jia

    2006-01-01

    Nowadays, many researches have been made on gallotannin biodegradation and have gained great success in further utilization. Some of industrial applications of these findings are in the production of tannase, the biotransformation of tannic acid to gallic acid or pyrogallol and detannification of food and fodder. Although ellagitannins have the typical C-C bound which is more difficult to be degraded than gallotannins, concerted efforts are still in progress to improve ellagitannin degradation and utilization. Currently, more attention is mainly focused on intestinal microflora biodegradation of tannins especially ellagitannins which can contribute to the definition of their bioavailability for both human beings and ruminants. Also there have been endeavours to utilize the tannin-degrading activity of different fungi for ellagitannin-rich biomass, which will facilitate application of tannin-degrading enzymes in strategies for improving industrial and livestock production. Due to the complicated structures of complex tannins and condensed tannins, the biodegradation of them is much more difficult and there are fewer researches on them. Therefore, the researches on the mechanisms of gallotannin and ellagitannin biodegradation can result in the overall understanding to the biodegradation of complex tannins and condensed tannins. Biodegradation of tannins is in an incipient stage and further studies have to be carried out to exploit the potential of various tannins for largescale applications in food, fodder, medicine and tannery effluent treatment. ((c) 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

  3. Biolimus-eluting biodegradable polymer-coated stent versus durable polymer-coated sirolimus-eluting stent in unselected patients receiving percutaneous coronary intervention (SORT OUT V)

    DEFF Research Database (Denmark)

    Christiansen, Evald Høj; Jensen, Lisette Okkels; Thayssen, Per

    2013-01-01

    Third-generation biodegradable polymer drug-eluting stents might reduce the risk of stent thrombosis compared with first-generation permanent polymer drug-eluting stents. We aimed to further investigate the effects of a biodegradable polymer biolimus-eluting stent compared with a durable polymer...

  4. Mucosal delivery of vaccines: role of mucoadhesive/biodegradable polymers.

    Science.gov (United States)

    Garg, Neeraj K; Mangal, Sharad; Khambete, Hemant; Sharma, Pradeep K; Tyagi, Rajeev K

    2010-06-01

    Majority of infectious microorganism make their gateway to the host through mucosal surfaces, such as gastrointestinal tract, nasal and vaginal tract. Mucosal immune response structured as sIgA can effectively prevent the attachment and invasion of the microorganism from mucosal surface and thereby serves as an efficient tool against infectious disease. There has been an increased demand for the development of novel vaccine that leads to the induction of immune response in systemic circulation as well as at mucosal surfaces against infectious disease. Mucosal delivery of vaccine provides basis for induction of both mucosal as well as systemic immune responses against the infectious organisms. However, a variety of factors such as mucociliary clearance, presence of deteriorating enzymes, pH extremes (GIT), low permeation and metabolic degradation limit the mucosal delivery of vaccine. Numerous strategies have been explored in the meadow of mucosal vaccination for the purpose of efficient antigen delivery through mucosal route(s). Polymeric carrier(s) such as nanoparticles and microparticles loaded with the antigen can serve as the basis for creation of important formulations for improved vaccine. Biodegradable and mucoadhesive polymeric carrier(s) seems to be most promising candidate for mucosal vaccine delivery. Several polymers from natural and synthetic origin, such as polylactide-co-glycolide, chitosan, alginate, carbopol, gelatin etc., have been explored for the efficient mucosal vaccine delivery and significant results have been obtained. This review outlines the polymers used in mucosal vaccine delivery with special reference to mucoadhesive/biodegradable polymers. This article also covers the recent patent granted in the field on polymeric carrier mediated mucosal vaccination.

  5. Preparation and Characterization of Zein and Zein-Chitosan Microspheres with Great Prospective of Application in Controlled Drug Release

    Directory of Open Access Journals (Sweden)

    Vinícius Müller

    2011-01-01

    Full Text Available Biomaterials applied as carriers for controlled drug delivery offer many advantages over the conventional systems. Among them, the increase of treatment effectiveness and also a significant reduction of toxicity, due to their biodegradability property, are some special features. In this work, microspheres based on the protein Zein (ZN and ZN associated to the natural polymer Chitosan (CHI were prepared and characterized. The microspheres of ZN and ZN/CHI were characterized by FT-IR spectroscopy and thermal analysis, and the morphology was analyzed by SEM images. The results confirmed the incorporation of CHI within the ZN-based microspheres. The morphological analysis showed that the CHI added increased the microspheres porosity when compared to the ZN microspheres. The chemical and physical characterization and the morphological analysis allow inferring that ZN/CHI microspheres are good candidates to act as a carrier for controlled drug release.

  6. Cyclosporine A loaded electrospun poly(D,L-lactic acid)/poly(ethylene glycol) nanofibers: drug carriers utilizable in local immunosuppression

    Czech Academy of Sciences Publication Activity Database

    Širc, Jakub; Hampejsová, Z.; Trnovská, J.; Kozlík, P.; Hrib, Jakub; Hobzová, Radka; Zajícová, Alena; Holáň, Vladimír; Bosáková, Z.

    2017-01-01

    Roč. 34, č. 7 (2017), s. 1391-1401 ISSN 0724-8741 R&D Projects: GA ČR(CZ) GA16-04863S; GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61389013 ; RVO:68378041 Keywords : cyclosporine A * drug release kinetics * LC-MS/MS Subject RIV: CD - Macromolecular Chemistry; JJ - Other Materials (UEM-P) OBOR OECD: Biochemical research methods; Nano-materials (production and properties) (UEM-P) Impact factor: 3.002, year: 2016

  7. Progress in nanotechnology-based drug carrier in designing of curcumin nanomedicines for cancer therapy: current state-of-the-art.

    Science.gov (United States)

    Ahmad, Mohammad Zaki; Alkahtani, Saad Ahmed; Akhter, Sohail; Ahmad, Farhan Jalees; Ahmad, Javed; Akhtar, Mohammad Shabib; Mohsin, Nehal; Abdel-Wahab, Basel A

    2016-01-01

    Comprehensive pharmacological screening of curcumin (CUR) has given the evidence that it is an excellent naturally occurring therapeutic moiety for cancer. It is very well tolerated with insignificant toxicity even after high doses of oral administration. Irrespective of its better quality as an anticancer agent, therapeutic application of CUR is hampered by its extremely low-aqueous solubility and poor bioavailability, rapid clearance and low-cellular uptake. A simple means of breaking up the restrictive factor of CUR is to perk-up its aqueous solubility, improve its bioavailability, protect it from degradation, and metabolism and potentiate its targeting capacity towards the cancer cell. The development in the field of nanomedicine has made excellent progresses toward enhancing the bioavailability of lipophilic drugs like CUR. Nanoparticles (NPs) are capable to deliver the CUR at specific area and thereby prevent it from physiological degradation and systemic clearance. In recent year, an assortment of nanomedicine-based novel drug delivery system has been designed to potentiate the bioavailability of CUR towards anticancer therapy. In this review, we discuss the recent development in the field of nanoCUR (NanoCur), including polymeric micelles, liposome, polymeric NPs, nanoemulsion, nanosuspension, solid lipid NPs (SLNPs), polymer conjugates, nanogel, etc. in anticancer application.

  8. Multifunctional porous silicon for therapeutic drug delivery and imaging.

    Science.gov (United States)

    Santos, Hélder A; Bimbo, Luis M; Lehto, Vesa-Pekka; Airaksinen, Anu J; Salonen, Jarno; Hirvonen, Jouni

    2011-09-01

    Major challenges in drug formulation are the poor solid state stability of drug molecules, poor dissolution/solubility and/or poor pharmacokinetic properties (bioavailability), which may lead to unreliable in vitro-in vivo (IVIV) correlation. To improve current therapeutical strategies, novel means to deliver poorly water soluble active pharmaceutical ingredients, as well as to target them to specific sites or cells in the body are needed. Biomedical applications of porous silicon (PSi) have been actively investigated during the last 10 years, especially in the areas of drug delivery and imaging, due to the biocompatibility and biodegradability of PSi materials, which makes them a potential candidate for controlled drug release. In addition, the unique pore sizes and easily functionalized surface properties of PSi materials allow high drug payloads and controlled kinetics from the drug release formulations. Modification of the PSi surface properties also facilitates biofunctionalization of the surface and the possibility to attach targeting moieties (e.g., antibodies and peptides), thus enabling effective targeting of the payload. In this review, we briefly address the production methodologies of PSi, and we will mainly present and discuss several examples about the biocompatibility of PSi, the most recent in vitro and in vivo applications of PSi as a carrier in drug/protein/peptide delivery and tissue engineering, as well as PSi as a platform for drug targeting and imaging.

  9. Polymeric micelles based on poly(ethylene glycol block poly(racemic amino acids hybrid polypeptides: conformation-facilitated drug-