Safe biodegradable fluorescent particles

Science.gov (United States)

Martin, Sue I [Berkeley, CA; Fergenson, David P [Alamo, CA; Srivastava, Abneesh [Santa Clara, CA; Bogan, Michael J [Dublin, CA; Riot, Vincent J [Oakland, CA; Frank, Matthias [Oakland, CA

2010-08-24

A human-safe fluorescence particle that can be used for fluorescence detection instruments or act as a safe simulant for mimicking the fluorescence properties of microorganisms. The particle comprises a non-biological carrier and natural fluorophores encapsulated in the non-biological carrier. By doping biodegradable-polymer drug delivery microspheres with natural or synthetic fluorophores, the desired fluorescence can be attained or biological organisms can be simulated without the associated risks and logistical difficulties of live microorganisms.

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.

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

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

Science.gov (United States)

Nakayama, Masamichi; Okano, Teruo

2005-07-01

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

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.

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.

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)

Biodegradation, Biocompatibility, and Drug Delivery in Poly(ω-pentadecalactone-co-p-dioxanone) Copolyesters

Science.gov (United States)

Liu, Jie; Jiang, Zhaozhong; Zhang, Shengmin; Liu, Chen; Gross, Richard A.; Kyriakides, Themis R.; Saltzman, W. Mark

2011-01-01

Poly(ω-pentadecalactone-co-p-dioxanone) [poly(PDL-co-DO)] copolyesters are copolymers of an isodimorphic system, which remain semicrystalline over the whole range of compositions. Here, we evaluated enzymatically synthesized poly(PDL-co-DO) copolymers as new materials for biomedical applications. In vivo experiments using mice showed that the copolyesters are well tolerated, with tissue responses that are comparable to poly(p-dioxanone). In addition, the copolymers were found to degrade hydrolytically at controlled rates over a period of several months under physiological conditions. The poly(PDL-co-DO) copolymers with up to 69 mol% DO units were successfully transformed to free-standing nanoparticles that are capable of encapsulating an anticancer drug, doxorubicin, or a polynucleotide, siRNA. Drug- or siRNA-loaded nanoparticles exhibited controlled and continuous release of agent over many weeks. In addition, siLUC-encapsulated poly(PDL-co-DO) nanoparticles were active in inhibiting luciferase gene expression in LUC-RKO cells. Because of substantial differences in structure and hydrophobicity between PDL and DO units, poly(PDL-co-DO) biodegradation rate and physical properties can be tuned over a wide range depending on the copolymer composition. Our results demonstrate that the semicrystalline and biodegradable poly(PDL-co-DO) copolyesters are promising biomaterials to serve as drug carriers, as well as potential raw materials for constructing bioabsorbable sutures and other medical devices. PMID:21641030

Novel flower-shaped albumin particles as controlled-release carriers for drugs to penetrate the round-window membrane.

Science.gov (United States)

Yu, Zhan; Yu, Min; Zhou, Zhimin; Zhang, Zhibao; Du, Bo; Xiong, Qingqing

2014-01-01

Controlled-release carriers for local drug delivery have attracted increasing attention for inner-ear treatment recently. In this paper, flower-shaped bovine serum albumin (FBSA) particles were prepared by a modified desolvation method followed by glutaraldehyde or heat denaturation. The size of the FBSA particles varied from 10 μm to 100 μm, and most were 50-80 μm. Heat-denatured FBSA particles have good cytocompatibility with a prolonged survival time for L929 cells. The FBSA particles were utilized as carriers to investigate the release behaviors of the model drug - rhodamine B. Rhodamine B showed a sustained-release effect and penetrated the round-window membrane of guinea pigs. We also confirmed the attachment of FBSA particles onto the round-window membrane by microscopy. The FBSA particles, with good biocompatibility, drug-loading capacity, adhesive capability, and biodegradability, may have potential applications in the field of local drug delivery for inner-ear disease treatment.

Cyclodextrin-based nanosponges as drug carriers

Directory of Open Access Journals (Sweden)

Francesco Trotta

2012-11-01

Full Text Available Cyclodextrin-based nanosponges, which are proposed as a new nanosized delivery system, are innovative cross-linked cyclodextrin polymers nanostructured within a three-dimensional network. This type of cyclodextrin polymer can form porous insoluble nanoparticles with a crystalline or amorphous structure and spherical shape or swelling properties. The polarity and dimension of the polymer mesh can be easily tuned by varying the type of cross-linker and degree of cross-linking. Nanosponge functionalisation for site-specific targeting can be achieved by conjugating various ligands on their surface. They are a safe and biodegradable material with negligible toxicity on cell cultures and are well-tolerated after injection in mice. Cyclodextrin-based nanosponges can form complexes with different types of lipophilic or hydrophilic molecules. The release of the entrapped molecules can be varied by modifying the structure to achieve prolonged release kinetics or a faster release. The nanosponges could be used to improve the aqueous solubility of poorly water-soluble molecules, protect degradable substances, obtain sustained delivery systems or design innovative drug carriers for nanomedicine.

Improvement of dissolution behavior of poorly water soluble drugs by biodegradable polymeric submicron carriers containing sparingly methylated β-cyclodextrin.

Science.gov (United States)

Singhavi, Dilesh J; Khan, Shagufta; Yeole, Pramod G

2013-04-01

The objective of this study was to develop submicron carriers of two drugs that are practically insoluble in water, i.e. meloxicam and aceclofenac, to improve their dissolution behavior. The phase solubility of the drugs was studied using different concentrations of sparingly methylated β-cyclodextrin, Kleptose(®) Crysmeβ (Crysmeb), in the presence and absence of 0.2 % w/v water-soluble chitosan. Drug-loaded submicron particles (SMPs) were prepared using chitosan chlorhydrate and Crysmeb by the ionotropic gelation method. The SMPs were characterized in terms of powder X-ray diffraction, Fourier transforms infrared spectroscopy, size determination, process yield, drug loading, encapsulation efficiency, surface morphology and in vitro release. The drug loading in the SMPs was enhanced in the presence of Crysmeb. The in vitro drug release was found to be enhanced with SMPs prepared using higher concentrations of Crysmeb. These results indicate that SMPs formed from chitosan chlorhydrate and Crysmeb are promising submicron carriers for enhancing the dissolution of meloxicam and aceclofenac.

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

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.

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.

HPMA Copolymer-Drug Conjugates with Controlled Tumor-Specific Drug Release.

Science.gov (United States)

Chytil, Petr; Koziolová, Eva; Etrych, Tomáš; Ulbrich, Karel

2018-01-01

Over the past few decades, numerous polymer drug carrier systems are designed and synthesized, and their properties are evaluated. Many of these systems are based on water-soluble polymer carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, or multidrug resistance inhibitors, all covalently bound to a carrier by a biodegradable spacer that enables controlled release of the active molecule to achieve the desired pharmacological effect. Among others, the synthetic polymer carriers based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers are some of the most promising carriers for this purpose. This review focuses on advances in the development of HPMA copolymer carriers and their conjugates with anticancer drugs, with triggered drug activation in tumor tissue and especially in tumor cells. Specifically, this review highlights the improvements in polymer drug carrier design with respect to the structure of a spacer to influence controlled drug release and activation, and its impact on the drug pharmacokinetics, enhanced tumor uptake, cellular trafficking, and in vivo antitumor activity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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

Institute of Scientific and Technical Information of China (English)

无

2001-01-01

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

Incorporation of in silico biodegradability screening in early drug development--a feasible approach?

Science.gov (United States)

Steger-Hartmann, Thomas; Länge, Reinhard; Heuck, Klaus

2011-05-01

The concentration of a pharmaceutical found in the environment is determined by the amount used by the patient, the excretion and metabolism pattern, and eventually by its persistence. Biological degradation or persistence of a pharmaceutical is experimentally tested rather late in the development of a pharmaceutical, often shortly before submission of the dossier to regulatory authorities. To investigate whether the aspect of persistence of a compound could be assessed early during drug development, we investigated whether biodegradation of pharmaceuticals could be predicted with the help of in silico tools. To assess the value of in silico prediction, we collected results for the OECD 301 degradation test ("ready biodegradability") of 42 drugs or drug synthesis intermediates and compared them to the prediction of the in silico tool BIOWIN. Of these compounds, 38 were predictable with BIOWIN, which is a module of the Estimation Programs Interface (EPI) Suite™ provided by the US EPA. The program failed to predict the two drugs which proved to be readily biodegradable in the degradation tests. On the other hand, BIOWIN predicted two compounds to be readily biodegradable which, however, proved to be persistent in the test setting. The comparison of experimental data with the predicted one resulted in a specificity of 94% and a sensitivity of 0%. The results of this study do not indicate that application of the biodegradation prediction tool BIOWIN is a feasible approach to assess the ready biodegradability during early drug development.

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.

Synthetic Lipoproteins as Carriers for Drug Delivery.

Science.gov (United States)

Huang, Gangliang; Liu, Yang; Huang, Hualiang

2016-01-01

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

Organized polysaccharide fibers as stable drug carriers

Science.gov (United States)

Janaswamy, Srinivas; Gill, Kristin L.; Campanella, Osvaldo H.; Pinal, Rodolfo

2013-01-01

Many challenges arise during the development of new drug carrier systems, and paramount among them are safety, solubility and controlled release requirements. Although synthetic polymers are effective, the possibility of side effects imposes restrictions on their acceptable use and dose limits. Thus, a new drug carrier system that is safe to handle and free from side effects is very much in need and food grade polysaccharides stand tall as worthy alternatives. Herein, we demonstrate for the first time the feasibility of sodium iota-carrageenan fibers and their distinctive water pockets to embed and release a wide variety of drug molecules. Structural analysis has revealed the existence of crystalline network in the fibers even after encapsulating the drug molecules, and iota-carrageenan maintains its characteristic and reproducible double helical structure suggesting that the composites thus produced are reminiscent of cocrystals. The melting properties of iota-carrageenan:drug complexes are distinctly different from those of either drug or iota-carrageenan fiber. The encapsulated drugs are released in a sustained manner from the fiber matrix. Overall, our research provides an elegant opportunity for developing effective drug carriers with stable network toward enhancing and/or controlling bioavailability and extending shelf-life of drug molecules using GRAS excipients, food polysaccharides, that are inexpensive and non–toxic. PMID:23544530

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

Science.gov (United States)

Hong, Xiaoyun; Wei, Liangming; Wu, Fei; Wu, Zaozhan; Chen, Lizhu; Liu, Zhenguo; Yuan, Weien

2013-01-01

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. PMID:24039404

Preparation of Biodegradable Oligo(lactides-Grafted Dextran Nanogels for Efficient Drug Delivery by Controlling Intracellular Traffic

Directory of Open Access Journals (Sweden)

Yuichi Ohya

2018-05-01

Full Text Available Nanogels, nanometer-sized hydrogel particles, have great potential as drug delivery carriers. To achieve effective drug delivery to the active sites in a cell, control of intracellular traffic is important. In this study, we prepared nanogels composed of dextran with oligolactide (OLA chains attached via disulfide bonds (Dex-g-SS-OLA that collapse under the reductive conditions of the cytosol to achieve efficient drug delivery. In addition, we introduced galactose (Gal residues on the nanogels, to enhance cellular uptake by receptor-mediated endocytosis, and secondary oligo-amine (tetraethylenepentamine groups, to aid in escape from endosomes via proton sponge effects. The obtained Dex-g-SS-OLA with attached Gal residues and tetraethylenepentamine (EI4 groups, EI4/Gal-Dex-g-SS-OLA, formed a nanogel with a hydrodynamic diameter of ca. 203 nm in phosphate-buffered solution. The collapse of the EI4/Gal-Dex-g-SS-OLA nanogels under reductive conditions was confirmed by a decrease in the hydrodynamic diameter in the presence of reductive agents. The specific uptake of the hydrogels into HepG2 cells and their intercellular behavior were investigated by flow cytometry and confocal laser scanning microscopy using fluorescence dye-labeled nanogels. Escape from the endosome and subsequent collapse in the cytosol of the EI4/Gal-Dex-g-SS-OLA were observed. These biodegradable nanogels that collapse under reductive conditions in the cytosol should have great potential as efficient drug carriers in, for example, cancer chemotherapy.

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.

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.

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

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

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

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

Preparation and characterization of biodegradable magnetic carriers by single emulsion-solvent evaporation

Energy Technology Data Exchange (ETDEWEB)

Liu Xianqiao [Departments of Neurology and Surgery (Neurosurgery), University of Chicago Pritzker School of Medicine, Chicago, IL (United States); Kaminski, Michael D. [Chemical Engineering Division, Argonne National Laboratory, Argonne, IL (United States); Riffle, Judy S. [Department of Chemistry, Virginia Tech, Blacksburg, VA (United States); Chen Haitao [Departments of Neurology and Surgery (Neurosurgery), University of Chicago Pritzker School of Medicine, Chicago, IL (United States); Torno, Michael [Departments of Neurology and Surgery (Neurosurgery), University of Chicago Pritzker School of Medicine, Chicago, IL (United States); Finck, Martha R. [Chemical Engineering Division, Argonne National Laboratory, Argonne, IL (United States); Taylor, LaToyia [Departments of Neurology and Surgery (Neurosurgery), University of Chicago Pritzker School of Medicine, Chicago, IL (United States); Rosengart, Axel J. [Departments of Neurology and Surgery (Neurosurgery), University of Chicago Pritzker School of Medicine, Chicago, IL (United States)]. E-mail: arosenga@uchicago.edu

2007-04-15

This paper describes a single emulsion-solvent evaporation protocol to prepare PEGylated biodegradable/biocompatible magnetic carriers by utilizing hydrophobic magnetite and a mixture of poly(D,L lactide-co-glycolide) (PLGA) and poly(lactic acid-block-polyethylene glycol) (PLA-PEG) (26:1 by mass) polymers. We characterized the magnetic microspheres in terms of morphology, composite microstructure, size and size distribution, and magnetic properties. Results show that the preparation produces magnetic microspheres with a good spherical morphology, small size (mean diameter of 1.2-1.5 {mu}m) by means of large size distributions, and magnetizations up to 20-30 emu/g of microspheres.

Preparation and characterization of biodegradable magnetic carriers by single emulsion-solvent evaporation

International Nuclear Information System (INIS)

Liu Xianqiao; Kaminski, Michael D.; Riffle, Judy S.; Chen Haitao; Torno, Michael; Finck, Martha R.; Taylor, LaToyia; Rosengart, Axel J.

2007-01-01

This paper describes a single emulsion-solvent evaporation protocol to prepare PEGylated biodegradable/biocompatible magnetic carriers by utilizing hydrophobic magnetite and a mixture of poly(D,L lactide-co-glycolide) (PLGA) and poly(lactic acid-block-polyethylene glycol) (PLA-PEG) (26:1 by mass) polymers. We characterized the magnetic microspheres in terms of morphology, composite microstructure, size and size distribution, and magnetic properties. Results show that the preparation produces magnetic microspheres with a good spherical morphology, small size (mean diameter of 1.2-1.5 μm) by means of large size distributions, and magnetizations up to 20-30 emu/g of microspheres

Radiation preparation of drug carriers based on poly(N-isopropylacrylamide) hydrogels, their loading capacities and controlled release rates for dexamethasone and tegafur

International Nuclear Information System (INIS)

Hoang Dang Sang; Nguyen Van Binh; Tran Bang Diep; Nguyen Thi Thom; Hoang Phuong Thao; Pham Duy Duong; Tran Minh Quynh

2015-01-01

Thermo-sensitive hydrogels have great potential in some applications. In order to use as the drug delivery systems, the hydrogels should be biocompatibility. New polymers with more biocompatibility and better biodegradability, and environmental friendly crosslinking agents would be necessary for the successful drug carriers. Poly (N-isopropylacrylamide-co-dimethylacrylamide) based hydrogels have been prepared from the admixture solutions of N-isopropylacrylamide (NIPA) and N,N’-dimethyl acrylamide (DMA) by radiation copolymerization and crosslinking at radiation dose of 20 kGy as reported in our previous study. Water swelling behaviour of the resulting hydrogels were much depended on their nature such as initial ratio of NIPA and DMA. The drug-loaded hydrogels were prepared by merging hydrogel in the solutions containing corresponding drugs. Loading capacity of the hydrogels were about 48.6 and 95.7 mg per g dried hydrogel for dexamethasone and tegafur. The release studies showed that the presence of ions in simulated body fluid and temperature of the solution much affecting to in vitro release behaviors of hydrogels for dexamethasone and tegafur. The release rates were fast for both drug models. The result also revealed that these drug carriers were biocompatibility without skin irritation, suggested the drug-loaded hydrogels may be used as controlled release drug delivery systems. (author)

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.

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

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.

Biodegradable microcontainers as an oral drug delivery system for poorly soluble drugs

DEFF Research Database (Denmark)

Nielsen, Line Hagner; Nagstrup, Johan; Keller, Stephan Sylvest

2013-01-01

PURPOSE: To fabricate microcontainers in biodegradable polylactic acid (PLLA) polymer films using hot embossing, and investigate the application of fabricated microcontainers as an oral drug delivery system for a poorly soluble drug. METHODS: For fabrication of the PLLA microcontainers, a film...... (produced by spray drying) using a simplified version of a screen printing technique. An enteric-resistant lid of Eudragit L-100 was subsequently spray coated onto the cavity of the microcontainers. Release of amorphous furosemide salt from the coated microcontainers was investigated using a μ-Diss profiler...... release from microcontainers in gastric medium, and facilitated an immediate release in the intestinal medium. The fabricated microcontainers therefore show considerable future potential as oral drug delivery systems....

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

Science.gov (United States)

Cheng, Kuo-Wei; Hsu, Shan-Hui

2017-01-01

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-(methylaminomethyl) anthracene [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.

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)

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.

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

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.

Enzymatic oxidative biodegradation of nanoparticles: Mechanisms, significance and applications

Energy Technology Data Exchange (ETDEWEB)

Vlasova, Irina I. [Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15219 (United States); Research Institute for Physico-Chemical Medicine, Federal Medico-Biological Agency, Moscow 119453 (Russian Federation); Kapralov, Alexandr A. [Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15219 (United States); Michael, Zachary P.; Burkert, Seth C. [Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Shurin, Michael R. [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261 (United States); Department of Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261 (United States); Star, Alexander [Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Shvedova, Anna A., E-mail: ats@cdc.gov [Pathology and Physiology Research Branch, Health Effects Laboratory Division (HELD), National Institute for Occupational Safety and Health (NIOSH) and Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV 26505 (United States); Kagan, Valerian E., E-mail: kagan@pitt.edu [Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15219 (United States); Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Departments of Pharmacology and Chemical Biology and Radiation Oncology, University of Pittsburgh, Pittsburgh, PA 15260 (United States)

2016-05-15

oxidative enzymatic machinery of inflammatory cells. • Peroxidase-generated oxidants are the reactive species executing the biodegradation. • Unmasked by GO binding peroxidase activity of cyt c biodegrades GO. • Professional phagocytes are accountable for the clearance of nanoparticles in vivo. • Carbonaceous nano-carriers of drugs protect against degradation of payloads.

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.

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.

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.

Novel flower-shaped albumin particles as controlled-release carriers for drugs to penetrate the round-window membrane

Directory of Open Access Journals (Sweden)

Yu Z

2014-07-01

Full Text Available Zhan Yu,1,* Min Yu,2,* Zhimin Zhou,3 Zhibao Zhang,3 Bo Du,3 Qingqing Xiong3 1Second Artillery General Hospital, Beijing, 2Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, College of Basic Medicine, China Medical University, Shenyang, 3Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Peking Union Medical College, Key Laboratory of Biomedical Material of Tianjin, Tianjin, People’s Republic of China *These authors contributed equallyto this work Abstract: Controlled-release carriers for local drug delivery have attracted increasing attention for inner-ear treatment recently. In this paper, flower-shaped bovine serum albumin (FBSA particles were prepared by a modified desolvation method followed by glutaraldehyde or heat denaturation. The size of the FBSA particles varied from 10 µm to 100 µm, and most were 50–80 µm. Heat-denatured FBSA particles have good cytocompatibility with a prolonged survival time for L929 cells. The FBSA particles were utilized as carriers to investigate the release behaviors of the model drug – rhodamine B. Rhodamine B showed a sustained-release effect and penetrated the round-window membrane of guinea pigs. We also confirmed the attachment of FBSA particles onto the round-window membrane by microscopy. The FBSA particles, with good biocompatibility, drug-loading capacity, adhesive capability, and biodegradability, may have potential applications in the field of local drug delivery for inner-ear disease treatment. Keywords: bovine serum albumin (BSA, controlled release, local delivery, round-window membrane

Injectable biodegradable carriers for the delivery of therapeutic agents and tissue engineering

OpenAIRE

Levato, Riccardo

2015-01-01

Premi Extraordinari de Doctorat, promoció 2014-2015. Àmbit d'Enginyeria Industrial The design of smart biomaterial devices plays a key role to improve the way conventional therapies are being delivered, and to promote the development of new approaches for advanced therapies, such as regenerative medicine and targeted drug release. Injectable biodegradable materials, such as those consisting of suspensions of polymeric particles, are highly versatile devices that can be delivered through mi...

Enhanced cytotoxicity of anticancer drug delivered by novel nanoscale polymeric carrier

Science.gov (United States)

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

2013-04-01

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

Enhanced cytotoxicity of anticancer drug delivered by novel nanoscale polymeric carrier

International Nuclear Information System (INIS)

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

2013-01-01

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

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...

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

Science.gov (United States)

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

2017-12-01

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

Drug targeting and the carriers. Application to chemoembolization and medical imaging

International Nuclear Information System (INIS)

Puisieux, F.; Benoit, J.P.; Roblot-Treupel, L.

1987-01-01

The last fifteen years have seen an increased interest in drug targeting which can be considered as a new way to control the body distribution of drugs when associated with an appropriate carrier. The systems currently studied possess different structures (macromolecular, vesicular and particular) and can be classified into carriers of first, second and third generation. After a brief review of the three types of carriers, this paper focuses on their respective interest in the different fields of radiology: carriers of first generation (microcapsules, microspheres) in chemoembolization, carriers of second generation (liposomes, nanocapsules, nanospheres) in conventional radiology, in computerized tomography, in scintigraphy, in RMN; carriers of third generation (monoclonal antibodies...) in immunoscintigraphy of tumors [fr

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.

The Research Progress of Targeted Drug Delivery Systems

Science.gov (United States)

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

2017-06-01

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

Biodegradable protein-based rockets for drug transportation and light-triggered release.

Science.gov (United States)

Wu, Zhiguang; Lin, Xiankun; Zou, Xian; Sun, Jianmin; He, Qiang

2015-01-14

We describe a biodegradable, self-propelled bovine serum albumin/poly-l-lysine (PLL/BSA) multilayer rocket as a smart vehicle for efficient anticancer drug encapsulation/delivery to cancer cells and near-infrared light controlled release. The rockets were constructed by a template-assisted layer-by-layer assembly of the PLL/BSA layers, followed by incorporation of a heat-sensitive gelatin hydrogel containing gold nanoparticles, doxorubicin, and catalase. These rockets can rapidly deliver the doxorubicin to the targeted cancer cell with a speed of up to 68 μm/s, through a combination of biocatalytic bubble propulsion and magnetic guidance. The photothermal effect of the gold nanoparticles under NIR irradiation enable the phase transition of the gelatin hydrogel for rapid release of the loaded doxorubicin and efficient killing of the surrounding cancer cells. Such biodegradable and multifunctional protein-based microrockets provide a convenient and efficient platform for the rapid delivery and controlled release of therapeutic drugs.

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.

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.

Targeted delivery of anti-tuberculosis drugs to macrophages: targeting mannose receptors

Science.gov (United States)

Filatova, L. Yu; Klyachko, N. L.; Kudryashova, E. V.

2018-04-01

The development of systems for targeted delivery of anti-tuberculosis drugs is a challenge of modern biotechnology. Currently, these drugs are encapsulated in a variety of carriers such as liposomes, polymers, emulsions and so on. Despite successful in vitro testing of these systems, virtually no success was achieved in vivo, because of low accessibility of the foci of infection located in alveolar macrophage cells. A promising strategy for increasing the efficiency of therapeutic action of anti-tuberculosis drugs is to encapsulate the agents into mannosylated carriers targeting the mannose receptors of alveolar macrophages. The review addresses the methods for modification of drug substance carriers, such as liposomes and biodegradable polymers, with mannose residues. The use of mannosylated carriers to deliver anti-tuberculosis agents increases the drug circulation time in the blood stream and increases the drug concentration in alveolar macrophage cells. The bibliography includes 113 references.

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.)

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.

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.

In Vivo Biological Evaluation of High Molecular Weight Multifunctional Acid-Degradable Polymeric Drug Carriers with Structurally Different Ketals.

Science.gov (United States)

Shenoi, Rajesh A; Abbina, Srinivas; Kizhakkedathu, Jayachandran N

2016-11-14

Understanding the influence of degradable chemical moieties on in vivo degradation, tissue distribution, and excretion is critical for the design of novel biodegradable drug carriers. Polyketals have recently emerged as a promising therapeutic delivery platform due to their ability to degrade under mild acidic intracellular compartments and generation of nontoxic degradation products. However, the effect of chemical structure of the ketal groups on the in vivo degradation, biodistribution, and pharmacokinetics of water-soluble ketal-containing polymers has not been explored. In the present work, we synthesized high molecular weight, water-soluble biodegradable hyperbranched polyglycerols (BHPGs) through the incorporation of structurally different ketal groups into the main chain of highly biocompatible polyglycerols. BHPGs showed pH and ketal group structure dependent degradation in buffer solutions. When the polymers were intravenously administered in mice, a strong dependence of in vivo degradation, biodistribution, and clearance on the ketal group structure was observed. All the BHPGs demonstrated degradation and clearance in vivo, with minimal tissue accumulation. Interestingly, an unanticipated degradation behavior of BHPGs with structurally different ketal groups was observed in vivo in comparison to their degradation in buffer solutions. BHPGs with cyclohexyl ketal (CHK) and cyclopentyl ketal (CPK) groups degraded much faster and were cleared from circulation much rapidly, while BHPG with glycerol hydroxy butanone ketal (GHBK) group degraded at a much slower rate and exhibited similar plasma half-life as that of nondegradable HPG. BHPG-GHBK also showed significantly lower tissue accumulation than nondegradable HPG after 30 days of administration. The difference in in vivo degradation may be attributed to the difference in hydrophobic characteristics of different ketal containing polymers, which may change their interaction with proteins and cells in vivo

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.

Application of two component biodegradable carriers in a particle-fixed biofilm airlift suspension reactor: development and structure of biofilms.

Science.gov (United States)

Hille, Andrea; He, Mei; Ochmann, Clemens; Neu, Thomas R; Horn, Harald

2009-01-01

Two component biodegradable carriers for biofilm airlift suspension (BAS) reactors were investigated with respect to development of biofilm structure and oxygen transport inside the biofilm. The carriers were composed of PHB (polyhydroxybutyrate), which is easily degradable and PCL (caprolactone), which is less easily degradable by heterotrophic microorganisms. Cryosectioning combined with classical light microscopy and CLSM was used to identify the surface structure of the carrier material over a period of 250 days of biofilm cultivation in an airlift reactor. Pores of 50 to several hundred micrometers depth are formed due to the preferred degradation of PHB. Furthermore, microelectrode studies show the transport mechanism for different types of biofilm structures, which were generated under different substrate conditions. At high loading rates, the growth of a rather loosely structured biofilm with high penetration depths of oxygen was found. Strong changes of substrate concentration during fed-batch mode operation of the reactor enhance the growth of filamentous biofilms on the carriers. Mass transport in the outer regions of such biofilms was mainly driven by advection.

Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers.

Science.gov (United States)

Ahuja, Naveen; Katare, Om Prakash; Singh, Bhupinder

2007-01-01

Role of various water-soluble carriers was studied for dissolution enhancement of a poorly soluble model drug, rofecoxib, using solid dispersion approach. Diverse carriers viz. polyethylene glycols (PEG 4000 and 6000), polyglycolized fatty acid ester (Gelucire 44/14), polyvinylpyrollidone K25 (PVP), poloxamers (Lutrol F127 and F68), polyols (mannitol, sorbitol), organic acid (citric acid) and hydrotropes (urea, nicotinamide) were investigated for the purpose. Phase-solubility studies revealed AL type of curves for each carrier, indicating linear increase in drug solubility with carrier concentration. The sign and magnitude of the thermodynamic parameter, Gibbs free energy of transfer, indicated spontaneity of solubilization process. All the solid dispersions showed dissolution improvement vis-à-vis pure drug to varying degrees, with citric acid, PVP and poloxamers as the most promising carriers. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Fickian diffusion. Solid state characterization of the drug-poloxamer binary system using XRD, FTIR, DSC and SEM techniques revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement in dissolution rate.

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

NARCIS (Netherlands)

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

2014-01-01

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

Biocompatibility of Chitosan Carriers with Application in Drug Delivery

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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.

Cathepsin B Cleavage of vcMMAE-Based Antibody-Drug Conjugate Is Not Drug Location or Monoclonal Antibody Carrier Specific.

Science.gov (United States)

Gikanga, Benson; Adeniji, Nia S; Patapoff, Thomas W; Chih, Hung-Wei; Yi, Li

2016-04-20

Antibody-drug conjugates (ADCs) require thorough characterization and understanding of product quality attributes. The framework of many ADCs comprises one molecule of antibody that is usually conjugated with multiple drug molecules at various locations. It is unknown whether the drug release rate from the ADC is dependent on drug location, and/or local environment, dictated by the sequence and structure of the antibody carrier. This study addresses these issues with valine-citrulline-monomethylauristatin E (vc-MMAE)-based ADC molecules conjugated at reduced disulfide bonds, by evaluating the cathepsin B catalyzed drug release rate of ADC molecules with different drug distributions or antibody carriers. MMAE drug release rates at different locations on ADC I were compared to evaluate the impact of drug location. No difference in rates was observed for drug released from the V(H), V(L), or C(H)2 domains of ADC I. Furthermore, four vc-MMAE ADC molecules were chosen as substrates for cathepsin B for evaluation of Michaelis-Menten parameters. There was no significant difference in K(M) or k(cat) values, suggesting that different sequences of the antibody carrier do not result in different drug release rates. Comparison between ADCs and small molecules containing vc-MMAE moieties as substrates for cathepsin B suggests that the presence of IgG1 antibody carrier, regardless of its bulkiness, does not impact drug release rate. Finally, a molecular dynamics simulation on ADC II revealed that the val-cit moiety at each of the eight possible conjugation sites was, on average, solvent accessible over 50% of its maximum solvent accessible surface area (SASA) during a 500 ns trajectory. Combined, these results suggest that the cathepsin cleavage sites for conjugated drugs are exposed enough for the enzyme to access and that the drug release rate is rather independent of drug location or monoclonal antibody carrier. Therefore, the distribution of drug conjugation at different

Nano carriers for drug transport across the blood-brain barrier.

Science.gov (United States)

Li, Xinming; Tsibouklis, John; Weng, Tingting; Zhang, Buning; Yin, Guoqiang; Feng, Guangzhu; Cui, Yingde; Savina, Irina N; Mikhalovska, Lyuba I; Sandeman, Susan R; Howel, Carol A; Mikhalovsky, Sergey V

2017-01-01

Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood-brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug-carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully

Solid lipid nanoparticles: A drug carrier system

Directory of Open Access Journals (Sweden)

Rashmi R Kokardekar

2011-01-01

Full Text Available Solid lipid nanoparticles (SLN are a type of nanoparticles. They are submicron colloidal carriers which are composed of physiological lipids, dispersed in water or in aqueous surfactant solutions. SLN have wide range of advantages over other types of nanoparticles. These include availability of large-scale production methods and no signs of cytotoxicity, which are main hindrances in the application of other types of nanoparticles. Hot and cold homogenization techniques are mainly employed for its production. They are mainly evaluated on the basis of their drug release profile and particle internal structure. The products based on SLN are under development. They have a very wide range of applications in cosmetics and pharmaceuticals. They can be applied for any purpose, for which nanoparticles have a distinct advantage. Thus, SLN can be used extensively as an alternative to the existing drug carrier systems, providing more flexibility with respect to the area of applications and also aspects for commercialization.

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

FY1995 biodegradable medical devices with molecular piston function; 1995 nendo bunshi piston kino wo yusuru iryoyo tainai bunkaisei soshi

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-03-01

The design of biodegradable medical devices with molecular piston function is examined by utilizing the structure of polyrotaxane. A polyrotaxane in which {beta}-cyclodextrins ({beta}-CDs) are threaded onto a block-copolymer of poly(ethylene glycol) (PEG) and poly(propylene glycol) (PPG) is synthesized, and its molecular dynamics is evaluated in terms of the movement of {beta}-CDs along the copolymer. Also, polyrotaxanes in which {alpha}-cyclodextrins ({alpha}-CDs) are threaded onto a PEG chain capped with biodegradable peptide moieties are synthesized, and their degradation characteristics concerning {alpha}-CD release behavior are clarified. Cellular response to these polyrotaxanes is examined as a bioactive molecule. The polyrotaxane composed of {beta}-CDs and the block-copolymer was synthesized, and both assembled and dispersed states of {alpha}-CDs were characterized along the copolymer in response to external stimulus (temperature). Further, the polyrotaxane composed of {alpha}-CDs and PEG were synthesize, and their facility as a drug carrier was evaluated in terms of the release of {alpha}-CDs triggered by the hydrolysis of terminal peptides. Also, these biodegradable polyrotaxanes were found to enhance the fluidity of plasma membranes and to regulate cellular activation (cytoplasmic calcium increase). Thus, the polyrotaxanes were concluded to be promising as novel biomaterials aiming for medical micromachines and polymeric drug carriers. (NEDO)

Low molecular mass chitosan as carrier for hydrodynamically balanced system for sustained delivery of ciprofloxacin hydrochloride

OpenAIRE

VERMA, ANURAG; BANSAL, ASHOK K.; GHOSH, AMITAVA; PANDIT, JAYANTA K.

2012-01-01

Chitosan has become a focus of major interest in recent years due to its excellent biocompatibility, biodegradability and non-toxicity. Although this material has already been extensively investigated in the design of different types of drug delivery systems, it is still little explored for stomach specific drug delivery systems. The objective of the present investigation was to explore the potential of low molecular mass chitosan (LMCH) as carrier for a hydrodynamically balanced system (HBS)...

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

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

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.

[In vitro drug release behavior of carrier made of porous glass ceramics].

Science.gov (United States)

Wang, De-ping; Huang, Wen-hai; Zhou, Nai

2002-09-01

To conduct the in vitro test on drug release of rifampin encapsulated in a carrier made of porous phosphate glass ceramics and to analyze main factors which affect the drug release rate. A certain quantitative of rifampin was sealed in a hollow cylindrical capsule which consisted of chopped calcium phosphate crystal fiber obtained from glass crystallization. The rifampin concentration was measured in the simulated physiological solution in which the capsule soaked. Rifampin could be released in a constant rate from the porous glass ceramic carrier in a long time. The release rate was dependent on the size of crystal fiber and the wall thickness of the capsule. This kind of calcium phosphate glass ceramics can be a candidate of the carrier materials used as long term drug therapy after osteotomy surgery.

Biodegradable 3D printed polymer microneedles for transdermal drug delivery.

Science.gov (United States)

Luzuriaga, Michael A; Berry, Danielle R; Reagan, John C; Smaldone, Ronald A; Gassensmith, Jeremiah J

2018-04-17

Biodegradable polymer microneedle (MN) arrays are an emerging class of transdermal drug delivery devices that promise a painless and sanitary alternative to syringes; however, prototyping bespoke needle architectures is expensive and requires production of new master templates. Here, we present a new microfabrication technique for MNs using fused deposition modeling (FDM) 3D printing using polylactic acid, an FDA approved, renewable, biodegradable, thermoplastic material. We show how this natural degradability can be exploited to overcome a key challenge of FDM 3D printing, in particular the low resolution of these printers. We improved the feature size of the printed parts significantly by developing a post fabrication chemical etching protocol, which allowed us to access tip sizes as small as 1 μm. With 3D modeling software, various MN shapes were designed and printed rapidly with custom needle density, length, and shape. Scanning electron microscopy confirmed that our method resulted in needle tip sizes in the range of 1-55 μm, which could successfully penetrate and break off into porcine skin. We have also shown that these MNs have comparable mechanical strengths to currently fabricated MNs and we further demonstrated how the swellability of PLA can be exploited to load small molecule drugs and how its degradability in skin can release those small molecules over time.

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.

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.

Fast dissolution of poorly water soluble drugs from fluidized bed coated nanocomposites: Impact of carrier size.

Science.gov (United States)

Azad, Mohammad; Moreno, Jacqueline; Bilgili, Ecevit; Davé, Rajesh

2016-11-20

Formation of core-shell nanocomposites of Fenofibrate and Itraconazole, model poorly water soluble drugs, via fluidized bed (FB) coating of their well-stabilized high drug loaded nanosuspensions is investigated. Specifically, the extent of dissolution enhancement, when fine carrier particles (sub-50μm) as opposed to the traditional large carrier particles (>300μm) are used, is examined. This allows testing the hypothesis that greatly increased carrier surface area and more importantly, thinner shell for finer carriers at the same drug loading can significantly increase the dissolution rate when spray-coated nanosuspensions are well-stabilized. Fine sub-50μm lactose (GranuLac ® 200) carrier particles were made fluidizable via dry coating with nano-silica, enabling decreased cohesion, fluidization and subsequent nanosuspension coating. For both drugs, 30% drug loaded suspensions were prepared via wet-stirred media milling using hydroxypropyl methyl cellulose and sodium dodecyl sulfate as stabilizers. The stabilizer concentrations were varied to affect the milled particle size and prepare a stable nanosuspension. The suspensions were FB coated onto hydrophilic nano-silica (M-5P) dry coated sub-50μm lactose (GranuLac ® 200) carrier particles or larger carrier particles of median size >300μm (PrismaLac ® 40). The resulting finer composite powders (sub-100μm) based on GranuLac ® 200 were freely flowing, had high bulk density, and had much faster, immediate dissolution of the poorly water-soluble drugs, in particular for Itraconazole. This is attributed to a much higher specific surface area of the carrier and corresponding thinner coating layer for fine carriers as opposed to those for large carrier particles. Copyright © 2016 Elsevier B.V. All rights reserved.

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

KAUST Repository

Croissant, Jonas; Fatieiev, Yevhen; Julfakyan, Khachatur; Lu, Jie; Emwas, Abdelhamid; Anjum, Dalaver; Omar, Haneen; Tamanoi, Fuyuhiko; Zink, Jeffrey; Khashab, Niveen M.

2016-01-01

We describe biodegradable mesoporous hybrid NPs in the presence of proteins, and its application for drug delivery. We synthesized oxamide-phenylene-based mesoporous organosilica nanoparticles (MON) in the absence of silica source which had a

Modeling Drug-Carrier Interaction in the Drug Release from Nanocarriers

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Like Zeng

2011-01-01

Full Text Available Numerous nanocarriers of various compositions and geometries have been developed for the delivery and release of therapeutic and imaging agents. Due to the high specific surface areas of nanocarriers, different mechanisms such as ion pairing and hydrophobic interaction need to be explored for achieving sustained release. Recently, we developed a three-parameter model that considers reversible drug-carrier interaction and first-order drug release from liposomes. A closed-form analytical solution was obtained. Here, we further explore the ability of the model to capture the release of bioactive molecules such as drugs and growth factors from various nanocarriers. A parameter study demonstrates that the model is capable of resembling major categories of drug release kinetics. We further fit the model to 60 sets of experimental data from various drug release systems, including nanoparticles, hollow particles, fibers, and hollow fibers. Additionally, bootstrapping is used to evaluate the accuracy of parameter determination and validate the model in selected cases. The simplicity and universality of the model and the clear physical meanings of each model parameter render the model useful for the design and development of new drug delivery systems.

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

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

2015-01-01

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

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

Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

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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.

Protein nanoparticles as drug delivery carriers for cancer therapy.

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

2014-01-01

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

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

International Nuclear Information System (INIS)

Jaiswal, Maneesh; Koul, Veena; Dinda, Amit K; Gupta, Asheesh

2010-01-01

A biodegradable semi-interpenetrating hydrogel network (semi-IPN) of polyacrylamide and gelatin was prepared using polycaprolactone diacrylate (mol. wt ∼ 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 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 t /M ∞ ≤ 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.

Smart surface coating of drug nanoparticles with cross-linkable polyethylene glycol for bio-responsive and highly efficient drug delivery

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Wei, Weijia; Zhang, Xiujuan; Chen, Xianfeng; Zhou, Mengjiao; Xu, Ruirui; Zhang, Xiaohong

2016-04-01

Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability and minimal premature release of therapeutic molecules during circulation in the blood stream. To meet this requirement, herein, we develop GSH-responsive and crosslinkable amphiphilic polyethylene glycol (PEG) molecules to modify carrier-free drug NPs. These PEG molecules can be cross-linked on the surface of the NPs to endow them with greater stability and the cross-link is sensitive to intracellular environment for bio-responsive drug release. With this elegant design, our experimental results show that the liberation of DOX from DOX-cross-linked PEG NPs is dramatically slower than that from DOX-non-cross-linked PEG NPs, and the DOX release profile can be controlled by tuning the concentration of the reducing agent to break the cross-link between PEG molecules. More importantly, in vivo studies reveal that the DOX-cross-linked PEG NPs exhibit favorable blood circulation half-life (>4 h) and intense accumulation in tumor areas, enabling effective anti-cancer therapy. We expect this work will provide a powerful strategy for stabilizing carrier-free nanomedicines and pave the way to their successful clinical applications in the future.Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability

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

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Anupama Shrivastav

2013-01-01

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

PEG-lipid micelles as drug carriers: physiochemical attributes, formulation principles and biological implication.

Science.gov (United States)

Gill, Kanwaldeep K; Kaddoumi, Amal; Nazzal, Sami

2015-04-01

PEG-lipid micelles, primarily conjugates of polyethylene glycol (PEG) and distearyl phosphatidylethanolamine (DSPE) or PEG-DSPE, have emerged as promising drug-delivery carriers to address the shortcomings associated with new molecular entities with suboptimal biopharmaceutical attributes. The flexibility in PEG-DSPE design coupled with the simplicity of physical drug entrapment have distinguished PEG-lipid micelles as versatile and effective drug carriers for cancer therapy. They were shown to overcome several limitations of poorly soluble drugs such as non-specific biodistribution and targeting, lack of water solubility and poor oral bioavailability. Therefore, considerable efforts have been made to exploit the full potential of these delivery systems; to entrap poorly soluble drugs and target pathological sites both passively through the enhanced permeability and retention (EPR) effect and actively by linking the terminal PEG groups with targeting ligands, which were shown to increase delivery efficiency and tissue specificity. This article reviews the current state of PEG-lipid micelles as delivery carriers for poorly soluble drugs, their biological implications and recent developments in exploring their active targeting potential. In addition, this review sheds light on the physical properties of PEG-lipid micelles and their relevance to the inherent advantages and applications of PEG-lipid micelles for drug delivery.

Genome-wide assessment of the carriers involved in the cellular uptake of drugs: a model system in yeast.

Science.gov (United States)

Lanthaler, Karin; Bilsland, Elizabeth; Dobson, Paul D; Moss, Harry J; Pir, Pınar; Kell, Douglas B; Oliver, Stephen G

2011-10-24

The uptake of drugs into cells has traditionally been considered to be predominantly via passive diffusion through the bilayer portion of the cell membrane. The recent recognition that drug uptake is mostly carrier-mediated raises the question of which drugs use which carriers. To answer this, we have constructed a chemical genomics platform built upon the yeast gene deletion collection, using competition experiments in batch fermenters and robotic automation of cytotoxicity screens, including protection by 'natural' substrates. Using these, we tested 26 different drugs and identified the carriers required for 18 of the drugs to gain entry into yeast cells. As well as providing a useful platform technology, these results further substantiate the notion that the cellular uptake of pharmaceutical drugs normally occurs via carrier-mediated transport and indicates that establishing the identity and tissue distribution of such carriers should be a major consideration in the design of safe and effective drugs.

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.

Semiconducting, biodegradable and bioactive fibers for drug delivery

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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.

Synthesis, characterization and in vitro cytotoxicity analysis of a novel cellulose based drug carrier for the controlled delivery of 5-fluorouracil, an anticancer drug

Science.gov (United States)

Anirudhan, Thayyath S.; Nima, Jayachandran; Divya, Peethambaran L.

2015-11-01

The present investigation concerns the development and evaluation of a novel drug delivery system, aminated-glycidylmethacrylate grafted cellulose-grafted polymethacrylic acid-succinyl cyclodextrin (Cell-g-(GMA/en)-PMA-SCD) for the controlled release of 5-Fluorouracil, an anticancer drug. The prepared drug carrier was characterized by FT-IR, XRD and SEM techniques. Binding kinetics and isotherm studies of 5-FU onto Cell-g-(GMA/en)-PMA-SCD were found to follow pseudo-second-order and Langmuir model respectively. Maximum binding capacity of drug carrier was found to be 149.09 mg g-1 at 37 °C. Swelling studies, in vitro release kinetics, drug loading efficiency and encapsulation efficiency of Cell-g-(GMA/en)-PMA-SCD were studied. The release kinetics was analyzed using Ritger-Peppas equation at pH 7.4. Cytotoxicity analysis on MCF-7 (human breast carcinoma) cells indicated that the drug carrier shows sustained and controlled release of drug to the target site. Hence, it is evident from this investigation that Cell-g-(GMA/en)-PMA-SCD could be a promising carrier for 5-FU.

pH-controlled drug loading and release from biodegradable microcapsules.

Science.gov (United States)

Zhao, Qinghe; Li, Bingyun

2008-12-01

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 makes use of 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 calcium carbonate (CaCO3) particles were synthesized and integrated with chondroitin sulfate (CS) through a reaction between sodium carbonate and calcium nitrate tetrahydrate 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 cross-link 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) permitted the subsequent selective control of drug loading and release. The CS-integrated microcapsules were loaded with a model drug, 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.

Antimicrobial drug susceptibility of Neisseria meningitidis strains isolated from carriers

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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.

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.

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

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

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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

Nanostructured lipid carriers versus microemulsions for delivery of the poorly water-soluble drug luteolin.

Science.gov (United States)

Liu, Ying; Wang, Lan; Zhao, Yiqing; He, Man; Zhang, Xin; Niu, Mengmeng; Feng, Nianping

2014-12-10

Nanostructured lipid carriers and microemulsions effectively deliver poorly water-soluble drugs. However, few studies have investigated their ability and difference in improving drug bioavailability, especially the factors contributed to the difference. Thus, this study was aimed at investigating their efficiency in bioavailability enhancement based on studying two key processes that occur in NLC and ME during traverse along the intestinal tract: the solubilization process and the intestinal permeability process. The nanostructured lipid carriers and microemulsions had the same composition except that the former were prepared with solid lipids and the latter with liquid lipids; both were evaluated for particle size and zeta potential. Transmission electron microscopy, differential scanning calorimetry, and X-ray diffraction were performed to characterize their properties. Furthermore, in vitro drug release, in situ intestinal absorption, and in vitro lipolysis were studied. The bioavailability of luteolin delivered using nanostructured lipid carriers in rats was compared with that delivered using microemulsions and suspensions. The in vitro analysis revealed different release mechanisms for luteolin in nanostructured lipid carriers and microemulsions, although the in situ intestinal absorption was similar. The in vitro lipolysis data indicated that digestion speed and extent were higher for microemulsions than for nanostructured lipid carriers, and that more of the former partitioned to the aqueous phase. The in vivo bioavailability analysis in rats indicated that the oral absorption and bioavailability of luteolin delivered using nanostructured lipid carriers and microemulsions were higher than those of luteolin suspensions. Nanostructured lipid carriers and microemulsions improved luteolin's oral bioavailability in rats. The rapid lipid digestion and much more drug solubilized available for absorption in microemulsions may contribute to better absorption and

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

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.

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.

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

Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies

Directory of Open Access Journals (Sweden)

Hsu YH

2014-09-01

Full Text Available Yung-Heng Hsu,1,2 Dave Wei-Chih Chen,1 Chun-Der Tai,3 Ying-Chao Chou,1,2 Shih-Jung Liu,2 Steve Wen-Neng Ueng,1 Err-Cheng Chan4 1Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, 2Department of Mechanical Engineering, Chang Gung University, Guishan Township, 3Graduate Institute of Medical Mechatronics, Chang Gung University, Guishan Township, 4School of Medical Technology, Chang Gung University, Guishan Township, Taiwan Abstract: We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics. Keywords: biodegradable nanofiber-enveloped plates, electrospinning, antibiotics, release characteristics

Gamma-sterilization-induced radicals in biodegradable drug delivery systems

International Nuclear Information System (INIS)

Maeder, K.; Swartz, H.M.; Domb, A.

1996-01-01

Electron paramagnetic resonance (EPR) spectroscopy (1.2 and 9.25 GHz, 25 o C) was used to characterize free radicals in gamma-ray sterilized biodegradable polymers of the type which are in clinical use. Free radicals were detected in all irradiated polymer samples. The temperature of irradiation (25 o vs dry ice temperature) had only a minor influence on the yield of radicals and the shape of the EPR spectra. In contrast, the composition of the polymers and the drugs incorporated in them did strongly influence the amount of radiation-induced free radicals and their reactivity. In general, polymers with high melting points and crystallinity had the highest yields of radicals observable at room temperature. We were able to use the free radicals induced by the usual sterilization procedures to follow the penetration of water and the degradation of the polymers in vitro and in vivo. The ability of in vivo EPR to follow drug delivery noninvasively and continuously in vivo, using the free radicals induced in the usual sterilization process indicates that this approach could be applied immediately for the characterization of these drug delivery systems in experimental animals and in the near future should be able to be used in human subjects. (author)

Magnetic polymer nanospheres for anticancer drug targeting

Energy Technology Data Exchange (ETDEWEB)

JurIkova, A; Csach, K; Koneracka, M; Zavisova, V; Tomasovicova, N; Lancz, G; Kopcansky, P; Timko, M; Miskuf, J [Institute of Experimental Physics, Slovak Academy of Sciences, 040 01 Kosice (Slovakia); Muckova, M, E-mail: akasard@saske.s [Hameln rds a.s., 900 01 Modra (Slovakia)

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.

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...... 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, boththe 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...

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.

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.

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-12-15

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

CHARACTERIZATION OF TERNARY SYSTEM OF POORLY SOLUBLE DRUG IN VARIOUS HYDROPHILIC CARRIERS

OpenAIRE

Vijay Kumar; Shankaraiah MM; Venkatesh JS; Rangaraju D; C.Nagesh

2011-01-01

The present study aims to experiment the solid dispersion of poorly water soluble drug fenbendazole as model drug. Fenbendazole is an Antihelmintic drug (BCS class 2).The purpose of this study was to enhance the dissolution of Fenbendazole by solid dispersions consisting of the drug, a polymeric carrier, Binary and ternary system were prepared by kneading method using hydrophilic polymers like polyvinylpyrrolidone K-25 (PVP K25), beta-cyclodextrin (BCD),mannitol and urea. The prepared form...

Elastic liposomes as novel carriers: recent advances in drug delivery

Science.gov (United States)

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

2017-01-01

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

Biological functionalization of drug delivery carriers to bypass size restrictions of receptor-mediated endocytosis independently from receptor targeting.

Science.gov (United States)

Ansar, Maria; Serrano, Daniel; Papademetriou, Iason; Bhowmick, Tridib Kumar; Muro, Silvia

2013-12-23

Targeting of drug carriers to cell-surface receptors involved in endocytosis is commonly used for intracellular drug delivery. However, most endocytic receptors mediate uptake via clathrin or caveolar pathways associated with ≤200-nm vesicles, restricting carrier design. We recently showed that endocytosis mediated by intercellular adhesion molecule 1 (ICAM-1), which differs from clathrin- and caveolae-mediated pathways, allows uptake of nano- and microcarriers in cell culture and in vivo due to recruitment of cellular sphingomyelinases to the plasmalemma. This leads to ceramide generation at carrier binding sites and formation of actin stress-fibers, enabling engulfment and uptake of a wide size-range of carriers. Here we adapted this paradigm to enhance uptake of drug carriers targeted to receptors associated with size-restricted pathways. We coated sphingomyelinase onto model (polystyrene) submicro- and microcarriers targeted to clathrin-associated mannose-6-phosphate receptor. In endothelial cells, this provided ceramide enrichment at the cell surface and actin stress-fiber formation, modifying the uptake pathway and enhancing carrier endocytosis without affecting targeting, endosomal transport, cell-associated degradation, or cell viability. This improvement depended on the carrier size and enzyme dose, and similar results were observed for other receptors (transferrin receptor) and cell types (epithelial cells). This phenomenon also enhanced tissue accumulation of carriers after intravenous injection in mice. Hence, it is possible to maintain targeting toward a selected receptor while bypassing natural size restrictions of its associated endocytic route by functionalization of drug carriers with biological elements mimicking the ICAM-1 pathway. This strategy holds considerable promise to enhance flexibility of design of targeted drug delivery systems.

Interpenetrating Polymer Networks as Innovative Drug Delivery Systems

Directory of Open Access Journals (Sweden)

Alka Lohani

2014-01-01

Full Text Available Polymers have always been valuable excipients in conventional dosage forms, also have shown excellent performance into the parenteral arena, and are now capable of offering advanced and sophisticated functions such as controlled drug release and drug targeting. Advances in polymer science have led to the development of several novel drug delivery systems. Interpenetrating polymer networks (IPNs have shown superior performances over the conventional individual polymers and, consequently, the ranges of applications have grown rapidly for such class of materials. The advanced properties of IPNs like swelling capacity, stability, biocompatibility, nontoxicity and biodegradability have attracted considerable attention in pharmaceutical field especially in delivering bioactive molecules to the target site. In the past few years various research reports on the IPN based delivery systems showed that these carriers have emerged as a novel carrier in controlled drug delivery. The present review encompasses IPNs, their types, method of synthesis, factors which affects the morphology of IPNs, extensively studied IPN based drug delivery systems, and some natural polymers widely used for IPNs.

(Glyco)-protein drug carriers with an intrinsic therapeutic activity : The concept of dual targeting

NARCIS (Netherlands)

Meijer, D.K F; Molema, Ingrid; Moolenaar, Frits; de Zeeuw, D; Swart, P.J

Dual targeting can in principle be achieved by using intrinsically active carriers that not only deliver the conjugated drug but also otherwise influence the pathological process. Potential carriers of this kind are monoclonal antibodies, certain interferons and interleukins, as well as certain

Recent trends in drug delivery system using protein nanoparticles.

Science.gov (United States)

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

2014-09-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-09-15

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

Peptide and low molecular weight proteins based kidney targeted drug delivery systems.

Science.gov (United States)

Xu, Pengfei; Zhang, Hailiang; Dang, Ruili; Jiang, Pei

2018-05-30

Renal disease is a worldwide public health problem, and unfortunately, the therapeutic index of regular drugs is limited. Thus, it is a great need to develop effective treatment strategies. Among the reported strategies, kidney-targeted drug delivery system is a promising method to increase renal efficacy and reduce extra-renal toxicity. In recent years, working as vehicles for targeted drug delivery, low molecular weight proteins (LMWP) and peptide have received immense attention due to their many advantages, such as selective accumulation in kidney, high drug loading capability, control over routes of biodegradation, convenience in modification at the amino terminus, and good biocompatibility. In this review, we describe the current LMWP and peptide carriers for kidney targeted drug delivery systems. In addition, we discuss different linking strategies between carriers and drugs. Furthermore, we briefly outline the current status and attempt to give an outlook on the further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Biodegradation of synthetic detergents in wastewater

African Journals Online (AJOL)

STORAGESEVER

2009-03-20

Mar 20, 2009 ... carrier gas at 37 psi. Hydrogen and air flow rates were 9 and 13 psi ... 24 h, by filtering the content of each set of test tubes using sterile filter paper while ..... environment-friendly, since it is biodegradable and it would enhance ...

Dual Functional Nanocarrier for Cellular Imaging and Drug Delivery in Cancer Cells Based on π-Conjugated Core and Biodegradable Polymer Arms.

Science.gov (United States)

Kulkarni, Bhagyashree; Surnar, Bapurao; Jayakannan, Manickam

2016-03-14

Multipurpose polymer nanoscaffolds for cellular imaging and delivery of anticancer drug are urgently required for the cancer therapy. The present investigation reports a new polymer drug delivery concept based on biodegradable polycaprolactone (PCL) and highly luminescent π-conjugated fluorophore as dual functional nanocarrier for cellular imaging and delivery vehicles for anticancer drug to cancer cells. To accomplish this goal, a new substituted caprolactone monomer was designed, and it was subjected to ring opening polymerization using a blue luminescent bishydroxyloligo-phenylenevinylene (OPV) fluorophore as an initiator. A series of A-B-A triblock copolymer building blocks with a fixed OPV π-core and variable chain biodegradable PCL arm length were tailor-made. These triblocks self-assembled in organic solvents to produce well-defined helical nanofibers, whereas in water they produced spherical nanoparticles (size ∼150 nm) with blue luminescence. The hydrophobic pocket of the polymer nanoparticle was found to be an efficient host for loading water insoluble anticancer drug such as doxorubicin (DOX). The photophysical studies revealed that there was no cross-talking between the OPV and DOX chromophores, and their optical purity was retained in the nanoparticle assembly for cellular imaging. In vitro studies revealed that the biodegradable PCL arm was susceptible to enzymatic cleavage at the intracellular lysosomal esterase under physiological conditions to release the loaded drugs. The nascent nanoparticles were found to be nontoxic to cancer cells, whereas the DOX-loaded nanoparticles accomplished more than 80% killing in HeLa cells. Confocal microscopic analysis confirmed the cell penetrating ability of the blue luminescent polymer nanoparticles and their accumulation preferably in the cytoplasm. The DOX loaded red luminescent polymer nanoparticles were also taken up by the cells, and the drug was found to be accumulated at the perinuclear environment

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.

Carrier-inside-carrier: polyelectrolyte microcapsules as reservoir for drug-loaded liposomes.

Science.gov (United States)

Maniti, Ofelia; Rebaud, Samuel; Sarkis, Joe; Jia, Yi; Zhao, Jie; Marcillat, Olivier; Granjon, Thierry; Blum, Loïc; Li, Junbai; Girard-Egrot, Agnès

2015-01-01

Conventional liposomes have a short life-time in blood, unless they are protected by a polymer envelope, most often polyethylene glycol. However, these stabilizing polymers frequently interfere with cellular uptake, impede liposome-membrane fusion and inhibit escape of liposome content from endosomes. To overcome such drawbacks, polymer-based systems as carriers for liposomes are currently developed. Conforming to this approach, we propose a new and convenient method for embedding small size liposomes, 30-100 nm, inside porous calcium carbonate microparticles. These microparticles served as templates for deposition of various polyelectrolytes to form a protective shell. The carbonate particles were then dissolved to yield hollow polyelectrolyte microcapsules. The main advantage of using this method for liposome encapsulation is that carbonate particles can serve as a sacrificial template for deposition of virtually any polyelectrolyte. By carefully choosing the shell composition, bioavailability of the liposomes and of the encapsulated drug can be modulated to respond to biological requirements and to improve drug delivery to the cytoplasm and avoid endosomal escape.

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

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.

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

Science.gov (United States)

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

2015-06-01

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

Assessment of hupu gum for its carrier property in the design and evaluation of solid mixtures of poorly water soluble drug - rofecoxib.

Science.gov (United States)

Vadlamudi, Harini Chowdary; Raju, Y Prasanna; Asuntha, G; Nair, Rahul; Murthy, K V Ramana; Vulava, Jayasri

2014-01-01

There are no reports about the pharmaceutical applications of hupu gum (HG). Hence the present study was undertaken to test its suitability in the dissolution enhancement of poorly water soluble drug. Rofecoxib (RFB) was taken as model drug. For comparison solid mixtures were prepared with carriers such as poly vinyl pyrrolidone (PVP), sodium starch glycollate (SSG) and guar gum (GG). Physical mixing (PM), co-grinding (CG), kneading (KT) and solvent evaporation (SE) techniques were used to prepare the solid mixtures, using all the carriers in different carrier and drug ratios. The solid mixtures were characterized by powder X-ray diffraction (XRD) and Fourier-transformed infrared spectroscopy (FTIR). There was a significant improvement in the dissolution rate of solid mixtures of HG, when compared with the solid mixtures of other carriers. There was an increase in dissolution rate with increase in concentration of HG upto 1:1 ratio of carrier and drug. No drug-carrier interaction was found by FTIR studies. XRD studies indicated reduction in crystallinity of the drug with increase in HG concentration. Hence HG could be a useful carrier for the dissolution enhancement of poorly water soluble drugs.

Positively Charged Nanostructured Lipid Carriers and Their Effect on the Dissolution of Poorly Soluble Drugs

Directory of Open Access Journals (Sweden)

Kyeong-Ok Choi

2016-05-01

Full Text Available The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC to increase its water solubility and bioavailability. Chitosan and HTCC-coated lipid particles had higher zeta-potential values than uncoated one over the whole pH ranges and improved encapsulation efficiency. In vitro drug release showed that all NLC formulations showed higher in vitro release efficiency than drug particle at pH 7.4. Furthermore, NLC formulation prepared with chitosan or HTCC represented good sustained release property. The results indicate that chitosan and HTCC can be excellent formulating excipients of lipid-based delivery carrier for improving poorly water soluble drug delivery.

Positively Charged Nanostructured Lipid Carriers and Their Effect on the Dissolution of Poorly Soluble Drugs.

Science.gov (United States)

Choi, Kyeong-Ok; Choe, Jaehyeog; Suh, Seokjin; Ko, Sanghoon

2016-05-20

The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC) to increase its water solubility and bioavailability. Chitosan and HTCC-coated lipid particles had higher zeta-potential values than uncoated one over the whole pH ranges and improved encapsulation efficiency. In vitro drug release showed that all NLC formulations showed higher in vitro release efficiency than drug particle at pH 7.4. Furthermore, NLC formulation prepared with chitosan or HTCC represented good sustained release property. The results indicate that chitosan and HTCC can be excellent formulating excipients of lipid-based delivery carrier for improving poorly water soluble drug delivery.

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.

An overview on the delivery of antitumor drug doxorubicin by carrier proteins.

Science.gov (United States)

Agudelo, D; Bérubé, G; Tajmir-Riahi, H A

2016-07-01

Serum proteins play an increasing role as drug carriers in the clinical settings. In this review, we have compared the binding modalities of anticancer drug doxorubicin (DOX) to three model carrier proteins, human serum albumin (HSA), bovine serum albumin (BSA) and milk beta-lactoglobulin (β-LG) in order to determine the potential application of these model proteins in DOX delivery. Molecular modeling studies showed stronger binding of DOX with HSA than BSA and β-LG with the free binding energies of -10.75 (DOX-HSA), -9.31 (DOX-BSA) and -8.12kcal/mol (DOX-β-LG). Extensive H-boding network stabilizes DOX-protein conjugation and played a major role in drug-protein complex formation. DOX complexation induced major alterations of HSA and BSA conformations, while did not alter β-LG secondary structure. The literature review shows that these proteins can potentially be used for delivery of DOX in vitro and in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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.

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.

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...

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.

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.

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.

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...

Well-Defined Poly(Ortho Ester Amides) for Potential Drug Carriers: Probing the Effect of Extra- and Intracellular Drug Release on Chemotherapeutic Efficacy.

Science.gov (United States)

Yan, Guoqing; Wang, Jun; Qin, Jiejie; Hu, Liefeng; Zhang, Panpan; Wang, Xin; Tang, Rupei

2017-07-01

To compare the chemotherapeutic efficacy determined by extra- and intracellular drug release strategies, poly(ortho ester amide)-based drug carriers (POEAd-C) with well-defined main-chain lengths, are successfully constructed by a facile method. POEAd-C3-doxorubicin (DOX) can be rapidly dissolved to release drug at tumoral extracellular pH (6.5-7.2), while POEAd-C6-DOX can rapidly release drug following gradual swelling at intracellular pH (5.0-6.0). In vitro cytotoxicity shows that POEAd-C3-DOX exhibits more toxic effect on tumor cells than POEAd-C6-DOX at extracellular pH, but POEAd-C6-DOX has stronger tumor penetration and inhibition in vitro and in vivo tumor models. So, POEAd-C6-DOX with the intracellular drug release strategy has stronger overall chemotherapeutic efficacy than POEAd-C3-DOX with extracellular drug release strategy. It is envisioned that these poly(ortho ester amides) can have great potential as drug carriers for efficient chemotherapy with further optimization. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Dissolution rate enhancement of the poorly water-soluble drug Tibolone using PVP, SiO2, and their nanocomposites as appropriate drug carriers.

Science.gov (United States)

Papadimitriou, Sofia; Bikiaris, Dimitrios

2009-09-01

Creation of immediate release formulations for the poorly water-soluble drug Tibolone through the use of solid dispersions (SDs). SD systems of Tibolone (Tibo) with poly(vinylpyrrolidone) (PVP), fumed SiO(2) nanoparticles, and their corresponding ternary systems (PVP/SiO(2)/Tibo) were prepared and studied in order to produce formulations with enhanced drug dissolution rates. The prepared SDs were characterized by the use of differential scanning calorimetry and wide-angle X-ray diffractometry techniques. Also dissolution experiments were performed. From the results it was concluded that PVP as well as SiO(2) can be used as appropriate carriers for the amorphization of Tibo, even when the drug is used at high concentrations (20-30%, w/w). This is due to the evolved interactions taking place between the drug and the used carriers, as was verified by Fourier transform infrared spectroscopy. At higher concentrations the drug was recrystallized. Similar are the observations on the ternary PVP/SiO(2)/Tibo SDs. The dissolution profiles of the drug in PVP/Tibo and SiO(2)/Tibo SDs are directly dependent on the physical state of the drug. Immediately release rates are observed in SD with low drug concentrations, in which Tibo was in amorphous state. However, these release profiles are drastically changed in the ternary PVP/SiO(2)/Tibo SDs. An immediate release profile is observed for low drug concentrations and an almost sustained release as the concentration of Tibo increases. This is due to the weak interactions that take place between PVP and SiO(2), which result in alterations of the characteristics of the carrier (PVP/SiO(2) nanocomposites). Immediate release formulation was created for Tibolone as well as new nanocomposite matrices of PVP/SiO((2)), which drastically change the release profile of the drug to a sustained delivery.

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

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

Science.gov (United States)

Nitta, Sachiko Kaihara; Numata, Keiji

2013-01-01

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

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

Directory of Open Access Journals (Sweden)

Keiji Numata

2013-01-01

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

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.

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

2014-12-19

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.

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

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

OpenAIRE

Sun, Dajun D.; Lee, Ping I.

2014-01-01

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 ...

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.

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.

Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers.

Science.gov (United States)

Nair, Madhavan; Guduru, Rakesh; Liang, Ping; Hong, Jeongmin; Sagar, Vidya; Khizroev, Sakhrat

2013-01-01

Although highly active anti-retroviral therapy has resulted in remarkable decline in the morbidity and mortality in AIDS patients, inadequately low delivery of anti-retroviral drugs across the blood-brain barrier results in virus persistence. The capability of high-efficacy-targeted drug delivery and on-demand release remains a formidable task. Here we report an in vitro study to demonstrate the on-demand release of azidothymidine 5'-triphosphate, an anti-human immunodeficiency virus drug, from 30 nm CoFe2O4@BaTiO3 magneto-electric nanoparticles by applying a low alternating current magnetic field. Magneto-electric nanoparticles as field-controlled drug carriers offer a unique capability of field-triggered release after crossing the blood-brain barrier. Owing to the intrinsic magnetoelectricity, these nanoparticles can couple external magnetic fields with the electric forces in drug-carrier bonds to enable remotely controlled delivery without exploiting heat. Functional and structural integrity of the drug after the release was confirmed in in vitro experiments with human immunodeficiency virus-infected cells and through atomic force microscopy, spectrophotometry, Fourier transform infrared and mass spectrometry studies.

Probing the mechanisms of drug release from amorphous solid dispersions in medium-soluble and medium-insoluble carriers.

Science.gov (United States)

Sun, Dajun D; Lee, Ping I

2015-08-10

The objective of the current study is to mechanistically differentiate the dissolution and supersaturation behaviors of amorphous drugs from amorphous solid dispersions (ASDs) based on medium-soluble versus medium-insoluble carriers under nonsink dissolution conditions through a direct head-to-head comparison. ASDs of indomethacin (IND) were prepared in several polymers which exhibit different solubility behaviors in acidic (pH1.2) and basic (pH7.4) dissolution media. The selected polymers range from water-soluble (e.g., PVP and Soluplus) and water-insoluble (e.g., ethylcellulose and Eudragit RL PO) to those only soluble in an acidic or basic dissolution medium (e.g., Eudragit E100, Eudragit L100, and HPMCAS). At 20wt.% drug loading, DSC and powder XRD analysis confirmed that the majority of incorporated IND was present in an amorphous state. Our nonsink dissolution results confirm that whether the carrier matrix is medium soluble determines the release mechanism of amorphous drugs from ASD systems which has a direct impact on the rate of supersaturation generation, thus in turn affecting the evolution of supersaturation in amorphous systems. For example, under nonsink dissolution conditions, the release of amorphous IND from medium-soluble carriers is governed by a dissolution-controlled mechanism leading to an initial surge of supersaturation followed by a sharp decline in drug concentration due to rapid nucleation and crystallization. In contrast, the dissolution of IND ASD from medium-insoluble carriers is more gradual as drug release is regulated by a diffusion-controlled mechanism by which drug supersaturation is built up gradually and sustained over an extended period of time without any apparent decline. Since several tested carrier polymers can be switched from soluble to insoluble by simply changing the pH of the dissolution medium, the results obtained here provide unequivocal evidence of the proposed transition of kinetic solubility profiles from the

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

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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.

Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model

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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

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

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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.

Application of nanohydrogels in drug delivery systems: recent patents review.

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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.

Biodegradable nanoparticles loaded with insulin-phospholipid complex for oral delivery: preparation, in vitro characterization and in vivo evaluation.

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Cui, Fude; Shi, Kai; Zhang, Liqiang; Tao, Anjin; Kawashima, Yoshiaki

2006-08-28

Biodegradable nanoparticles loaded with insulin-phospholipid complex were prepared by a novel reverse micelle-solvent evaporation method, in which soybean phosphatidylcholine (SPC) was employed to improve the liposolubility of insulin, and biodegradable polymers as carrier materials to control drug release. Solubilization study, IR and X-ray diffraction analysis were employed to prove the complex formation. The effects of key parameters such as polymer/SPC weight ratio, organic phase and polymer type on the properties of the nanoparticles were investigated. Spherical particles of 200 nm mean diameter and a narrow size distribution were obtained under optimal conditions. The drug entrapment efficiency was up to 90%. The in vitro drug release was characterized by an initial burst and subsequent delayed release in both pH 6.8 and pH 1.2 dissolution mediums. The specific modality of drug release, i.e., free or SPC-combined, was investigated in the aid of ultracentrifugation and ultrafiltration methods. The influence of polymer type on the drug release was also discussed. The pharmacological effects of the nanoparticles made of PLGA 50/50 (Av.Mw 9500) were further evaluated to confirm their potential suitability for oral delivery. Intragastric administration of the 20 IU/kg nanoparticles reduced fasting plasma glucose levels to 57.4% within the first 8 h of administration and this continued for 12 h. PK/PD analysis indicated that 7.7% of oral bioavailability relative to subcutaneous injection was obtained.

Mucoadhesive Polymer Hyaluronan as Biodegradable Cationic/Zwitterionic-Drug Delivery Vehicle

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Francisco Torrens

2015-01-01

Full Text Available Mucoadhesive polymers in pharmaceutical formulations release drugs in mucosal areas. They interact and fix to mucus via molecular interpenetration, etc., which increase drug bioavailability. Polymers physicochemical properties affect formulation mucoadhesion, rheological behaviour and drug absorption. Hyaluronan (HA is selected as a mucoadhesive and biodegradable polymer. Geometric, topological and fractal analyses are carried out with program TOPO. Reference calculations are performed with algorithm GEPOL. Procedure TOPO underestimates molecular volume by 0.7%. Error results 5% in surface area and derived topological indices. Solvent-accessible surface is undercalculated by 3%: from hexamer HA to HA·3Ca and hydrate, the hydrophobic term rises by 42% and decays by 26%, and hydrophilic part drops by 14% and rises by 58% in agreement with the number of H-bonds. Accessibility rises by 9% and decays by 8%. Fractal dimension is underevaluated by 1% and for HA it results 1.566; on going to HA·3Ca and hydrate it rises by 2% and 1%. External-atoms dimension increases by 11%: for HA it results 1.725. When going to HA·3Ca and hydrate, it augments by 4% and 0.3%. On going from HA to HA·3Ca and hydrate, nonburied minus molecular dimension enlarges by 20% and decays by 9%. The hydrate globularity is lower than for water, Ca2+ and averages of O-atoms in HA. Ca2+ rugosity is smaller than for hydrate, averages of O-atoms in HA and water. Ca2+ and water accessibilities are greater than for hydrate. As cations exchange in HA·3Ca requires Ca2+ alteration, rises of drug zwitterionic character and acidic pH increase absorption.

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

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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.

IMPROVEMENT OF SOLUBILITY OF BADLY WATER SOLUBLE DRUG (IBUPROFEN) BY USING SURFACTANTS AND CARRIERS

OpenAIRE

Md. Zakaria Faruki*, Rishikesh, Elizabeth Razzaque, Mohiuddin Ahmed Bhuiyan

2013-01-01

ABSTRACT: Although there was a great interest in solid dispersion systems during the past four decades to increase dissolution rate and bioavailability of badly water-soluble drugs, their profitable use has been very limited, primarily because of manufacturing difficulties and stability problems. In this study solid solutions of drugs were generally produced by fusion method. The drug along with the excipients (surfactants and carriers) was heated first and then hardened by cooling to room te...

Biodegradable Alginate-Chitosan Hollow Nanospheres for Codelivery of Doxorubicin and Paclitaxel for the Effect of Human Lung Cancer A549 Cells

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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.

Novel biodegradable sandwich-structured nanofibrous drug-eluting membranes for repair of infected wounds: an in vitro and in vivo study

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Chan EC

2012-02-01

Full Text Available Dave Wei-Chih Chen1,2, Jun-Yi Liao3, Shih-Jung Liu2, Err-Cheng Chan41Department of Orthopedic Surgery, Chang Gung Memorial Hospital, 2Department of Mechanical Engineering, 3Graduate Institute of Medical Mechatronics, 4School of Medical Technology, Chang Gung University, Kwei-San, Tao-Yuan, TaiwanBackground: The purpose of this study was to develop novel sandwich-structured nanofibrous membranes to provide sustained-release delivery of vancomycin, gentamicin, and lidocaine for repair of infected wounds.Methods: To prepare the biodegradable membranes, poly(D, L-lactide-co-glycolide (PLGA, collagen, and various pharmaceuticals, including vancomycin, gentamicin, and lidocaine, were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into sandwich-structured membranes with PLGA/collagen as the surface layers and PLGA/drugs as the core. An elution method and a high-pressure liquid chromatography assay were used to characterize in vivo and in vitro drug release from the membranes. In addition, repair of infected wounds in rats was studied. Histological examination of epithelialization and granulation at the wound site was also performed.Results: The biodegradable nanofibrous membranes released large amounts of vancomycin and gentamicin (well above the minimum inhibition concentration and lidocaine in vivo for more than 3 weeks. A bacterial inhibition test was carried out to determine the relative activity of the antibiotics released. The bioactivity ranged from 40% to 100%. The nanofibrous membranes were functionally active in treating infected wounds, and were very effective as accelerators in early-stage wound healing.Conclusion: Using the electrospinning technique, we will be able to manufacture biodegradable, biomimetic, nanofibrous, extracellular membranes for long-term delivery of various drugs.Keywords: nanofibrous, sandwich-structured, drug-eluting membranes, electrospinning, release characteristics, repair, wound

Comparison of different zeolite framework types as carriers for the oral delivery of the poorly soluble drug indomethacin.

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Karavasili, Christina; Amanatiadou, Elsa P; Kontogiannidou, Eleni; Eleftheriadis, Georgios K; Bouropoulos, Nikolaos; Pavlidou, Eleni; Kontopoulou, Ioanna; Vizirianakis, Ioannis S; Fatouros, Dimitrios G

2017-08-07

Microporous zeolites of distinct framework types, textural properties and crystal morphologies namely BEA, ZSM and NaX, have been employed as carriers to assess their effect on modulating the dissolution behavior of a BCS II model drug (indomethacin). Preparation of the loaded carriers via the incipient wetness method induced significant drug amorphization for the BEA and NaX samples, as well as high drug payloads. The stability of the amorphous drug content was retained after stressing test evaluation of the porous carriers. The dissolution profile of loaded indomethacin was evaluated in simulated gastric fluid (pH 1.2) and simulated intestinal fluids FaSSIF (fasted) and FeSSIF (fed state) conditions and was found to be dependent on the aluminosilicate ratio of the zeolites and the degree of crystalline drug content. The feasibility of the zeolitic particles as oral drug delivery systems was appraised with cytocompatibility and cellular toxicity studies in Caco-2 cultures in a time- and dose-dependent manner by means of the MTT assay and flow cytometry analysis, respectively. Intracellular accumulation of the zeolite particles was observed with no apparent cytotoxic effects at the lower concentrations tested, rendering such microporous zeolites pertinent candidates in oral drug delivery applications. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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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.

Modified local diatomite as potential functional drug carrier--A model study for diclofenac sodium.

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Janićijević, Jelena; Krajišnik, Danina; Čalija, Bojan; Vasiljević, Bojana Nedić; Dobričić, Vladimir; Daković, Aleksandra; Antonijević, Milan D; Milić, Jela

2015-12-30

Diatomite makes a promising candidate for a drug carrier because of its high porosity, large surface area, modifiable surface chemistry and biocompatibility. Herein, refined diatomite from Kolubara coal basin, which complied with the pharmacopoeial requirements for heavy metals content and microbiological quality, was used as a starting material. Inorganic modification of the starting material was performed through a simple, one-step procedure. Significant increase in adsorbent loading with diclofenac sodium (DS) was achieved after the modification process (∼373mg/g) which enabled the preparation of comprimates containing therapeutic dose of the adsorbed drug. Adsorption of DS onto modified diatomite resulted in the alteration of the drug's XRD pattern and FTIR spectrum. In vitro drug release studies in phosphate buffer pH 7.5 demonstrated prolonged DS release over 8h from comprimates containing DS adsorbed on modified diatomite (up to 37% after 8h) and those containing physical mixture of the same composition (up to 45% after 8h). The results of in vivo toxicity testing on mice pointed on potential safety of both unmodified (starting) and modified diatomite. All these findings favor the application of diatomite as a potential functional drug carrier. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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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.

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

International Nuclear Information System (INIS)

Xu, Jing; Luan, Shujuan; Qin, Benkai; Wang, Yingying; Wang, Kai; Qi, Peilan; Song, Shiyong

2016-01-01

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.

Rhodamine/Nanodiamond as a System Model for Drug Carrier.

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Reina, G; Orlanducci, S; Cairone, C; Tamburri, E; Lenti, S; Cianchetta, I; Rossi, M; Terranova, M L

2015-02-01

In this paper we present some strategies that are being developed in our labs towards enabling nanodiamond-based applications for drug delivery. Rhodamine B (RhB) has been choosen as model molecule to study the loading of nanodiamonds with active moieties and the conditions for their controlled release. In order to test the chemical/physical interactions between functionalized detonation nanodiamond (DND) and complex molecules, we prepared and tested different RhB@DND systems, with RhB adsorbed or linked by ionic bonding to the DND surface. The chemical state of the DND surfaces before conjugation with the RhB molecules, and the chemical features of the DND-RhB interactions have been deeply analysed by coupling DND with Au nanoparticles and taking advantage of surface enhanced Raman spectroscopy SERS. The effects due to temperature and pH variations on the process of RhB release from the DND carrier have been also investigated. The amounts of released molecules are consistent with those required for effective drug action in conventional therapeutic applications, and this makes the DND promising nanostructured cargos for drug delivery applications.

Development of drug-loaded chitosan hollow nanoparticles for delivery of paclitaxel to human lung cancer A549 cells.

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Jiang, Jie; Liu, Ying; Wu, Chao; Qiu, Yang; Xu, Xiaoyan; Lv, Huiling; Bai, Andi; Liu, Xuan

2017-08-01

In this study, biodegradable chitosan hollow nanospheres (CHN) were fabricated using polystyrene nanospheres (PS) as templates. CHN were applied to increase the solubility of poorly water-soluble drugs. The lung cancer drug paclitaxel (PTX), which is used as a model drug, was loaded into CHN by the adsorption equilibrium method. The drug-loaded sample (PTX-CHN) offered sustained PTX release and good bioavailability. The state characterization of PTX by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) showed that the PTX absorbed into CHN existed in an amorphous state. An in vitro toxicity experiment indicated that CHN were nontoxic as carriers of poorly water-soluble drugs. The PTX-CHN produced a marked inhibition of lung cancer A549 cells proliferation and encouraged apoptosis. A cell uptake experiment indicated that PTX-CHN was successfully taken up by lung cancer A549 cells. Furthermore, a degradation experiment revealed that CHN were readily biodegradable. These findings state clearly that CHN can be regarded as promising biomaterials for lung cancer treatment.

[Pharmaceutical application of cyclodextrins as multi-functional drug carriers].

Science.gov (United States)

Uekama, Kaneto

2004-12-01

Owing to the increasingly globalized nature of the cyclodextrin (CyD)-related science and technology, development of the CyD-based pharmaceutical formulation is rapidly progressing. The pharmaceutically useful CyDs are classified into hydrophilic, hydrophobic, and ionic derivatives. Because of the multi-functional characteristics and bioadaptability, these CyDs are capable of alleviating the undesirable properties of drug molecules through the formation of inclusion complexes or the form of CyD/drug conjugates. This review outlines the current application of CyDs in drug delivery and pharmaceutical formulation, focusing on the following evidences. 1) The hydrophilic CyDs enhance the rate and extent of bioavailability of poorly water-soluble drugs. 2) The amorphous CyDs such as 2-hydroxypropyl-beta-CyD are useful for inhibition of polymorphic transition and crystallization rates of drugs during storage. 3) The delayed release formulation can be obtained by the use of enteric type CyDs such as O-carboxymethyl-O-ethyl-beta-CyD. 4) The hydrophobic CyDs are useful for modification of the release site and/or time profile of water-soluble drugs with prolonged therapeutic effects. 5) The branched CyDs are particularly effective in inhibiting the adsorption to hydrophobic surface of containers and aggregation of polypeptide and protein drugs. 6) The combined use of different CyDs and/or pharmaceutical additives can serve as more functional drug carriers, improving efficacy and reducing side effects. 7) The CyD/drug conjugates may provide a versatile means for the constructions of not only colonic delivery system but also site-specific drug release system, including gene delivery. On the basis of the above-mentioned knowledge, the advantages and limitations of CyDs in the design of advanced dosage forms will be discussed.

Elastic liposomes as novel carriers: recent advances in drug delivery

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Hussain A

2017-07-01

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

Drug release from core-shell PVA/silk fibroin nanoparticles fabricated by one-step electrospraying.

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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.

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.)

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

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...... to macrophages. All drug-loaded PLGA and PEC films were amorphous indicating good miscibility of the drug in the polymers, even at high drug loading (up to 50wt.%). Polymer degradation studies showed that PLGA degraded slowly via bulk erosion while PEC degraded more rapidly and near-linearly via enzyme mediated...... 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...

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

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.

A polymeric nanoparticle consisting of mPEG-PLA-Toco and PLMA-COONa as a drug carrier: improvements in cellular uptake and biodistribution.

Science.gov (United States)

Yi, Yilwoong; Kim, Jae Hong; Kang, Hye-Won; Oh, Hun Seung; Kim, Sung Wan; Seo, Min Hyo

2005-02-01

To evaluate a new polymeric nanoparticulate drug delivery formulation that consists of two components: i) an amphiphilic diblock copolymer having tocopherol moiety at the end of the hydrophobic block in which the hydrophobic tocopherol moiety increases stability of hydrophobic core of the nanoparticle in aqueous medium; and ii) a biodegradable copolyester having carboxylate end group that is capable of forming ionic complex with positively charged compounds such as doxorubicin. A doxourubicin-loaded polymeric nanoparticle (Dox-PNP) was prepared by solvent evaporation method. The entrapment efficiency, size distribution, and in vitro release profile at various pH conditions were characterized. In vitro cellular uptake was investigated by confocal microscopy, flow cytometry, and MTT assay using drug-sensitive and drug-resistant cell lines. Pharmacokinetics and biodistribution were evaluated in rats and tumor-bearing mice. Doxorubicin (Dox) was efficiently loaded into the PNP (higher than 95% of entrapment efficiency), and the diameter of Dox-PNP was in the range 20-25 nm with a narrow size distribution. In Vitro study showed that Dox-PNP exhibited higher cellular uptake into both human breast cancer cell (MCF-7) and human uterine cancer cell (MES-SA) than free doxorubicin solution (Free-Dox), especially into drug-resistant cells (MCF-7/ADR and MES-SA/Dx-5). In pharmacokinetics and tissue distribution study, the bioavailability of Dox-PNP calculated from the area under the blood concentration-time curve (AUC) was 69.8 times higher than that of Free-Dox in rats, and Dox-PNP exhibited 2 times higher bioavailability in tumor tissue of tumor-bearing mice. Dox-PNP exhibited enhanced cellular uptake of the drug. In the cytotoxic activity study, this improved cellular uptake was proved to be more advantageous in drug-resistant cell. Dox-PNP exhibited much higher bioavailability in blood plasma and more drug accumulation in tumor tissue than conventional doxorubicin

Monoglyceride-based self-assembling copolymers as carriers for poorly water-soluble drugs.

Science.gov (United States)

Rouxhet, L; Dinguizli, M; Latere Dwan'isa, J P; Ould-Ouali, L; Twaddle, P; Nathan, A; Brewster, M E; Rosenblatt, J; Ariën, A; Préat, V

2009-12-01

To develop self-assembling polymers forming polymeric micelles and increasing the solubility of poorly soluble drugs, amphiphilic polymers containing a hydrophilic PEG moiety and a hydrophobic moiety derived from monoglycerides and polyethers were designed. The biodegradable copolymers were obtained via a polycondensation reaction of polyethylene glycol (PEG), monooleylglyceride (MOG) and succinic anhydride (SA). Polymers with molecular weight below 10,000 g/mol containing a minimum of 40 mol% PEG and a maximum of 10 mol% MOG self-assembled spontaneously in aqueous media upon gentle mixing. They formed particles with a diameter of 10 nm although some aggregation was evident. The critical micellar concentration varied between 3x10(-4) and 4x10(-3) g/ml, depending on the polymer. The cloud point (> or = 66 degrees C) and flocculation point (> or = 0.89 M) increased with the PEG chain length. At a 1% concentration, the polymers increased the solubility of poorly water-soluble drug candidates up to 500-fold. Drug solubility increased as a function of the polymer concentration. HPMC capsules filled with these polymers disintegrated and released model drugs rapidly. Polymer with long PEG chains had a lower cytotoxicity (MTT test) on Caco-2 cells. All of these data suggest that the object polymers, in particular PEG1000/MOG/SA (45/5/50) might be potential candidates for improving the oral biopharmaceutical performance of poorly soluble drugs.

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

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.

Piroxicam loaded alginate beads obtained by prilling/microwave tandem technique: morphology and drug release.

Science.gov (United States)

Aquino, Rita P; Auriemma, Giulia; d'Amore, Matteo; D'Ursi, Anna Maria; Mencherini, Teresa; Del Gaudio, Pasquale

2012-07-01

This paper presents a tandem technique, based on the combination of prilling and microwave (MW) assisted treatments, to produce biodegradable alginate carriers of piroxicam with different drug controlled release behaviours. Results showed that alginate/piroxicam beads demonstrated high encapsulation efficiency and very narrow dimensional distribution. Beads dried by MW retained shape and size distribution of the hydrated particles while drying rate was strongly increased compared to convective drying processes. Moreover, different MW irradiation regimes promoted interactions between the drug and alginate matrix, affected drug polymorphism as well as inner and surface matrix structure leading to different piroxicam release profiles. High level MW irradiation led to beads with highly porous and swellable matrix able to release piroxicam in few minutes in the intestine while convective drying produced gastro-resistant beads that exhibit sustained piroxicam release (total release in 5.5h) in intestinal environment. On these results the tandem technique prilling/MW irradiation appears to be promising to obtain alginate carrier with tailored NSAIDs release depending on drug characteristics and MW irradiation. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

Tailored dendritic core-multishell nanocarriers for efficient dermal drug delivery: A systematic top-down approach from synthesis to preclinical testing.

Science.gov (United States)

Hönzke, Stefan; Gerecke, Christian; Elpelt, Anja; Zhang, Nan; Unbehauen, Michael; Kral, Vivian; Fleige, Emanuel; Paulus, Florian; Haag, Rainer; Schäfer-Korting, Monika; Kleuser, Burkhard; Hedtrich, Sarah

2016-11-28

Drug loaded dendritic core-multishell (CMS) nanocarriers are of especial interest for the treatment of skin diseases, owing to their striking dermal delivery efficiencies following topical applications. CMS nanocarriers are composed of a polyglycerol core, connected by amide-bonds to an inner alkyl shell and an outer methoxy poly(ethylene glycol) shell. Since topically applied nanocarriers are subjected to biodegradation, the application of conventional amide-based CMS nanocarriers (10-A-18-350) has been limited by the potential production of toxic polyglycerol amines. To circumvent this issue, three tailored ester-based CMS nanocarriers (10-E-12-350, 10-E-15-350, 10-E-18-350) of varying inner alkyl chain length were synthesized and comprehensively characterized in terms of particle size, drug loading, biodegradation and dermal drug delivery efficiency. Dexamethasone (DXM), a potent drug widely used for the treatment of inflammatory skin diseases, was chosen as a therapeutically relevant test compound for the present study. Ester- and amide-based CMS nanocarriers delivered DXM more efficiently into human skin than a commercially available DXM cream. Subsequent in vitro and in vivo toxicity studies identified CMS (10-E-15-350) as the most biocompatible carrier system. The anti-inflammatory potency of DXM-loaded CMS (10-E-15-350) nanocarriers was assessed in TNFα supplemented skin models, where a significant reduction of the pro-inflammatory cytokine IL-8 was seen, with markedly greater efficacy than commercial DXM cream. In summary, we report the rational design and characterization of tailored, biodegradable, ester-based CMS nanocarriers, and their subsequent stepwise screening for biocompatibility, dermal delivery efficiency and therapeutic efficacy in a top-down approach yielding the best carrier system for topical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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.

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

Implications of formulation design on lipid-based nanostructured carrier system for drug delivery to brain.

Science.gov (United States)

Salunkhe, Sachin S; Bhatia, Neela M; Bhatia, Manish S

2016-05-01

The aim of present investigation was to formulate and develop lipid-based nanostructured carriers (NLCs) containing Idebenone (IDE) for delivery to brain. Attempts have been made to evaluate IDE NLCs for its pharmacokinetic and pharmacodynamic profile through the objective of enhancement in bioavailability and effectivity of drug. Nanoprecipitation technique was used for development of drug loaded NLCs. The components solid lipid Precirol ATO 5, oil Miglyol 840, surfactants Tween 80 and Labrasol have been screened out for formulation development by consideration of preformulation parameters including solubility, Required Hydrophilic lipophilic balance (HLB) of lipids and stability study. Developed IDE NLCs were subjected for particle size, zeta potential, entrapment efficiency (%EE), crystallographic investigation, transmission electron microscopy, in vitro drug release, pharmacokinetics, in vivo and stability study. Formulation under investigation has particle size 174.1 ± 2.6 nm, zeta potential -18.65 ± 1.13 mV and% EE 90.68 ± 2.90. Crystallographic studies exemplified for partial amorphization of IDE by molecularly dispersion within lipid crust. IDE NLCs showed drug release 93.56 ± 0.39% at end of 24 h by following Higuchi model which necessitates for appropriate drug delivery with enhancement in bioavailability of drug by 4.6-fold in plasma and 2.8-fold in brain over plain drug loaded aqueous dispersions. In vivo studies revealed that effect of drug was enhanced by prepared lipid nanocarriers. IDE lipid-based nanostructured carriers could have potential for efficient drug delivery to brain with enhancement in bioavailability of drug over the conventional formulations.

Biodegradable Polydepsipeptides

Directory of Open Access Journals (Sweden)

Jintang Guo

2009-02-01

Full Text Available This paper reviews the synthesis, characterization, biodegradation and usage of bioresorbable polymers based on polydepsipeptides. The ring-opening polymerization of morpholine-2,5-dione derivatives using organic Sn and enzyme lipase is discussed. The dependence of the macroscopic properties of the block copolymers on their structure is also presented. Bioresorbable polymers based on polydepsipeptides could be used as biomaterials in drug controlled release, tissue engineering scaffolding and shape-memory materials.

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

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.

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.

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

Biodistribution of doxorubicin and nanostructured ferrocarbon carrier particles in organism during magnetically controlled drug delivery

Energy Technology Data Exchange (ETDEWEB)

Kuznetsov, Anatoly A.; Filippov, Victor I.; Nikolskaya, Tatiana A. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation); Budko, Andrei P. [Oncological Center, Russian Academy of Medical Sciences, Moscow (Russian Federation); Kovarskii, Alexander L. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation); Zontov, Sergei V. [Oncological Center, Russian Academy of Medical Sciences, Moscow (Russian Federation); Kogan, Boris Ya. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation); Kuznetsov, Oleg A. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation)], E-mail: kuznetsov_oa@yahoo.com

2009-05-15

Biodistribution of doxorubicin and ferrocarbon carrier particles in organism during and after magnetically controlled anti-tumor drug delivery and deposition was studied. Animal tests show high concentration of the cytostatic drug in the target zone, while its concentration is three orders of magnitude lower in bloodstream and other organs. A significant depot of the drug remains on the deposited particles days after the procedure. Macrophages actively phagocytose the ferrocarbon (FeC) particles and remain viable long enough to carry them to the lymph nodes.

Biodistribution of doxorubicin and nanostructured ferrocarbon carrier particles in organism during magnetically controlled drug delivery

International Nuclear Information System (INIS)

Kuznetsov, Anatoly A.; Filippov, Victor I.; Nikolskaya, Tatiana A.; Budko, Andrei P.; Kovarskii, Alexander L.; Zontov, Sergei V.; Kogan, Boris Ya.; Kuznetsov, Oleg A.

2009-01-01

Biodistribution of doxorubicin and ferrocarbon carrier particles in organism during and after magnetically controlled anti-tumor drug delivery and deposition was studied. Animal tests show high concentration of the cytostatic drug in the target zone, while its concentration is three orders of magnitude lower in bloodstream and other organs. A significant depot of the drug remains on the deposited particles days after the procedure. Macrophages actively phagocytose the ferrocarbon (FeC) particles and remain viable long enough to carry them to the lymph nodes.

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.

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

Science.gov (United States)

Sun, Dajun D; Lee, Ping I

2014-02-01

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.

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

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

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.

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.

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 ...

Evaluation of oil biodegradation using time warping and PCA

Energy Technology Data Exchange (ETDEWEB)

Christensen, J.H. [Royal Veterinary and Agricultural Univ., Thorvaldsensvej (Denmark). Dept. of Natural Sciences; Hansen, A.B. [National Environmental Research Inst., Roskilde (Denmark). Dept. of Environmental Chemistry and Microbiology; Andersen, O. [Roskilde Univ., Roskilde (Denmark). Dept. of Life Sciences and Chemistry

2005-07-01

The effects of biodegradation on the composition of stranded oil after the Baltic Carrier oil spill in March 2001 was evaluated using a newly developed multivariate statistical methodology. Gas chromatography and mass spectrometry provided data on the oil compounds and oil biodegradation was determined by applying weighted least square principal component analysis to the preprocessed chromatograms of methylphenanthrenes and methyldibenzothiophenes. One principal component explained 46 per cent of the variation in the complete data set. Samples collected immediately after the spill and 2.5 months after the spill did not exhibit changes in isomer composition. However, the isomer patterns changed in samples collected between 6.5 and 16.5 months after the spill. Samples collected after 8.5 months were the most greatly affected. An evaluation of the degradation patterns suggest that time warping and multivariate statistical methods can successfully identify links between spill samples and can determine how chemical composition will respond to biodegradation processes. 27 refs., 1 tab., 3 figs.

Evaluation of oil biodegradation using time warping and PCA

International Nuclear Information System (INIS)

Christensen, J.H.; Hansen, A.B.; Andersen, O.

2005-01-01

The effects of biodegradation on the composition of stranded oil after the Baltic Carrier oil spill in March 2001 was evaluated using a newly developed multivariate statistical methodology. Gas chromatography and mass spectrometry provided data on the oil compounds and oil biodegradation was determined by applying weighted least square principal component analysis to the preprocessed chromatograms of methylphenanthrenes and methyldibenzothiophenes. One principal component explained 46 per cent of the variation in the complete data set. Samples collected immediately after the spill and 2.5 months after the spill did not exhibit changes in isomer composition. However, the isomer patterns changed in samples collected between 6.5 and 16.5 months after the spill. Samples collected after 8.5 months were the most greatly affected. An evaluation of the degradation patterns suggest that time warping and multivariate statistical methods can successfully identify links between spill samples and can determine how chemical composition will respond to biodegradation processes. 27 refs., 1 tab., 3 figs

Lactic Acid Polymers as Biodegradable Carriers of Fluoroquinolones: An In Vitro Study

OpenAIRE

Kanellakopoulou, Kyriaki; Kolia, Maria; Anastassiadis, Antonios; Korakis, Themistoklis; Giamarellos-Bourboulis, Evangelos J.; Andreopoulos, Andreas; Dounis, Eleftherios; Giamarellou, Helen

1999-01-01

A biodegradable polymer of dl-dilactide that facilitates release of ciprofloxacin or pefloxacin at levels exceeding MICs for the causative microorganisms of chronic osteomyelitis is described. Duration and peak of release were found to depend on the molecular weight of the polymer. Its characteristics make it promising for treating chronic bone infections.

Nanoprecipitation process: From encapsulation to drug delivery.

Science.gov (United States)

Martínez Rivas, Claudia Janeth; Tarhini, Mohamad; Badri, Waisudin; Miladi, Karim; Greige-Gerges, Hélène; Nazari, Qand Agha; Galindo Rodríguez, Sergio Arturo; Román, Rocío Álvarez; Fessi, Hatem; Elaissari, Abdelhamid

2017-10-30

Drugs encapsulation is a suitable strategy in order to cope with the limitations of conventional dosage forms such as unsuitable bioavailability, stability, taste, and odor. Nanoprecipitation technique has been used in the pharmaceutical and agricultural research as clean alternative for other drug carrier formulations. This technique is based on precipitation mechanism. Polymer precipitation occurs after the addition of a non-solvent to a polymer solution in four steps mechanism: supersaturation, nucleation, growth by condensation, and growth by coagulation that leads to the formation of polymer nanoparticles or aggregates. The scale-up of laboratory-based nanoprecipitation method shows a good reproducibility. In addition, flash nanoprecipitation is a good strategy for industrial scale production of nanoparticles. Nanoprecipitation is usually used for encapsulation of hydrophobic or hydrophilic compounds. Nanoprecipitation was also shown to be a good alternative for the encapsulation of natural compounds. As a whole, process and formulation related parameters in nanoprecipitation technique have critical effect on nanoparticles characteristics. Biodegradable or non-biodegradable polymers have been used for the preparation of nanoparticles intended to in vivo studies. Literature studies have demonstrated the biodistribution of the active loaded nanoparticles in different organs after administration via various routes. In general, in vitro drug release from nanoparticles prepared by nanoprecipitation includes two phases: a first phase of "burst release" which is followed by a second phase of prolonged release. Moreover, many encapsulated active molecules have been commercialized in the pharmaceutical market. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhancement of solubility and bioavailability of ambrisentan by solid dispersion using Daucus carota as a drug carrier: formulation, characterization, in vitro, and in vivo study.

Science.gov (United States)

Deshmane, Subhash; Deshmane, Snehal; Shelke, Santosh; Biyani, Kailash

2018-06-01

Ambrisentan is an US FDA approved drug, it is the second oral endothelin A receptor antagonist known for the treatment of pulmonary arterial hypertension, but its oral administration is limited due to its poor water solubility. Hence, the objective of the investigation was focused on enhancement of solubility and bioavailability of ambrisentan by solid dispersion technique using natural Daucus carota extract as drug carrier. Drug carrier was evaluated for solubility, swelling index, viscosity, angle of repose, hydration capacity, and acute toxicity test (LD 50 ). Ambrisentan was studied for the saturation solubility, phase solubility, and Gibbs free energy change. Compatibility of drug and the natural carrier was confirmed by DSC, FTIR, and XRD. Solid dispersions were evaluated for drug content, solubility, morphology, in vitro, and in vivo study. Screening of the natural carrier showed the desirable properties like water solubility, less swelling index, less viscosity, and acute toxicity study revealed no any clinical symptoms of toxicity. Drug and carrier interaction study confirmed the compatibility to consider its use in the formulation. Formed particles were found to be spherical with smooth surface. In vitro studies revealed higher drug release from the solid dispersion than that of the physical mixture. Bioavailability study confirms the increased absorption and bioavailability by oral administration of solid dispersion. Hence, it can be concluded that the natural Daucus carota extract can be the better alternative source for the preparation of solid dispersion and/or other dosage forms for improving solubility and bioavailability.

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

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.

Lyophilized silica lipid hybrid (SLH) carriers for poorly water-soluble drugs: physicochemical and in vitro pharmaceutical investigations.

Science.gov (United States)

Yasmin, Rokhsana; Tan, Angel; Bremmell, Kristen E; Prestidge, Clive A

2014-09-01

Lyophilization was investigated to produce a powdery silica-lipid hybrid (SLH) carrier for oral delivery of poorly water-soluble drugs. The silica to lipid ratio, incorporation of cryoprotectant, and lipid loading level were investigated as performance indicators for lyophilized SLH carriers. Celecoxib, a nonsteroidal anti-inflammatory drug, was used as the model poorly soluble moiety to attain desirable physicochemical and in vitro drug solubilization properties. Scanning electron microscopy and confocal fluorescence imaging verified a nanoporous, homogenous internal matrix structures of the lyophilized SLH particles, prepared from submicron triglyceride emulsions and stabilized by porous silica nanoparticles (Aerosil 380), similar to spray-dried SLH. 20-50 wt % of silica in the formulation have shown to produce nonoily SLH agglomerates with complete lipid encapsulation. The incorporation of a cryoprotectant prevented irreversible aggregation of the silica-stabilized droplets during lyophilization, thereby readily redispersing in water to form micrometre-sized particles (water-soluble therapeutics is confirmed. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Intimate Coupling of Photocatalysis and Biodegradation for Degrading Phenol Using Different Light Types: Visible Light vs UV Light.

Science.gov (United States)

Zhou, Dandan; Xu, Zhengxue; Dong, Shanshan; Huo, Mingxin; Dong, Shuangshi; Tian, Xiadi; Cui, Bin; Xiong, Houfeng; Li, Tingting; Ma, Dongmei

2015-07-07

Intimate coupling of photocatalysis and biodegradation (ICPB) technology is attractive for phenolic wastewater treatment, but has only been investigated using UV light (called UPCB). We examined the intimate coupling of visible-light-induced photocatalysis and biodegradation (VPCB) for the first time. Our catalyst was prepared doping both of Er(3+) and YAlO3 into TiO2 which were supported on macroporous carriers. The macroporous carriers was used to support for the biofilms as well. 99.8% removal efficiency of phenol was achieved in the VPCB, and this was 32.6% higher than that in the UPCB. Mineralization capability of UPCB was even worse, due to less adsorbable intermediates and cell lysis induced soluble microbial products release. The lower phenol degradation in the UPCB was due to the serious detachment of the biofilms, and then the microbes responsible for phenol degradation were insufficient due to disinfection by UV irradiation. In contrast, microbial communities in the carriers were well protected under visible light irradiation and extracellular polymeric substances secretion was enhanced. Thus, we found that the photocatalytic reaction and biodegradation were intimately coupled in the VPCB, resulting in 64.0% removal of dissolved organic carbon. Therefore, we found visible light has some advantages over UV light in the ICPB technology.

A novel bio-safe phase separation process for preparing open-pore biodegradable polycaprolactone microparticles.

Science.gov (United States)

Salerno, Aurelio; Domingo, Concepción

2014-09-01

Open-pore biodegradable microparticles are object of considerable interest for biomedical applications, particularly as cell and drug delivery carriers in tissue engineering and health care treatments. Furthermore, the engineering of microparticles with well definite size distribution and pore architecture by bio-safe fabrication routes is crucial to avoid the use of toxic compounds potentially harmful to cells and biological tissues. To achieve this important issue, in the present study a straightforward and bio-safe approach for fabricating porous biodegradable microparticles with controlled morphological and structural features down to the nanometer scale is developed. In particular, ethyl lactate is used as a non-toxic solvent for polycaprolactone particles fabrication via a thermal induced phase separation technique. The used approach allows achieving open-pore particles with mean particle size in the 150-250 μm range and a 3.5-7.9 m(2)/g specific surface area. Finally, the combination of thermal induced phase separation and porogen leaching techniques is employed for the first time to obtain multi-scaled porous microparticles with large external and internal pore sizes and potential improved characteristics for cell culture and tissue engineering. Samples were characterized to assess their thermal properties, morphology and crystalline structure features and textural properties. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Polyphosphoester nanoparticles as biodegradable platform for delivery of multiple drugs and siRNA

Directory of Open Access Journals (Sweden)

Elzeny H

2017-02-01

Full Text Available Hadeel Elzeny,1,* Fuwu Zhang,2,* Esraa N Ali,1 Heba A Fathi,1 Shiyi Zhang,3 Richen Li,2 Mohamed A El-Mokhtar,4 Mostafa A Hamad,5 Karen L Wooley,2,6 Mahmoud Elsabahy1,6–8 1Assiut International Center of Nanomedicine, Al-Rajhy Liver Hospital, Assiut University, Assiut, Egypt; 2Departments of Chemistry, Chemical Engineering and Materials Science and Engineering, Texas A&M University, College Station, TX, USA; 3School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Microbiology and Immunology, Faculty of Medicine, 5Department of Surgery, Faculty of Medicine, Assiut University, Assiut, Egypt; 6Laboratory for Synthetic-Biologic Interactions, Department of Chemistry, Texas A&M University, College Station, TX, USA; 7Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, 8Misr University for Science and Technology, 6th of October City, Egypt *These authors contributed equally to this work Abstract: Delivery of multiple therapeutics and/or diagnostic agents to diseased tissues is challenging and necessitates the development of multifunctional platforms. Among the various strategies for design of multifunctional nanocarriers, biodegradable polyphosphoester (PPE polymers have been recently synthesized via a rapid and simple synthetic strategy. In addition, the chemical structure of the polymer could be tuned to form nanoparticles with varying surface chemistries and charges, which have shown exceptional safety and biocompatibility as compared to several commercial agents. The purpose of this study was to exploit a mixture of PPE nanoparticles of cationic and neutral surface charges for multiple delivery of anticancer drugs (ie, sorafenib and paclitaxel and nucleic acids (ie, siRNA. Cationic PPE polymers could efficiently complex siRNA, and the stability of the nanoparticles could be maintained in physiological solutions and upon freeze-drying and were able to deliver si

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.

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.

Micro- and Nano-Carrier Mediated Intra-Articular Drug Delivery Systems for the Treatment of Osteoarthritis

Directory of Open Access Journals (Sweden)

Zhiyue Zhang

2012-01-01

Full Text Available The objective of this paper is to provide readers with current developments of intra-articular drug delivery systems. In recent years, although the search for a clinically successful ideal carrier is ongoing, sustained-release systems, such as polymeric micro- and nanoparticles, liposomes, and hydrogels, are being extensively studied for intra-articular drug delivery purposes. The advantages associated with long-acting preparations include a longer effect of the drug in the action site and a reduced risk of infection due to numerous injections consequently. This paper discusses the recent developments in the field of intra-articular sustained-release delivery systems for the treatment of osteoarthritis.

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

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.

{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.

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.

Preparation of Polysaccharide-Based Microspheres by a Water-in-Oil Emulsion Solvent Diffusion Method for Drug Carriers

Directory of Open Access Journals (Sweden)

Yodthong Baimark

2013-01-01

Full Text Available Polysaccharide-based microspheres of chitosan, starch, and alginate were prepared by the water-in-oil emulsion solvent diffusion method for use as drug carriers. Blue dextran was used as a water-soluble biomacromolecular drug model. Scanning electron microscopy showed sizes of the resultant microspheres that were approximately 100 μm or less. They were spherical in shape with a rough surface and good dispersibility. Microsphere matrices were shown as a sponge. Drug loading efficiencies of all the microspheres were higher than 80%, which suggested that this method has potential to prepare polysaccharide-based microspheres containing a biomacromolecular drug model for drug delivery applications.

Characterization of Polycaprolactone and Rice Husk Silica Composite (PCL-SiO2) by E-Spinning to Apply Supporter for Drug Release

Science.gov (United States)

Song, Sinae; Hilonga, Askwar; Taik Kim, Hee

2018-03-01

Polycaprolactone (PCL) is an interesting material to apply biomedical field owing to its biodegradability and biocompatibility which is suitable for a specific site with longer healing times. Blending the polymer with other materials has degradation property improved with the effective and economic method. This study was conducted to fabricate supporter based on Polycaprolactone and Rice husk silica (PCL-SiO2) by using electrospinning. Nano-porous silica in the composite was synthesized from rice husk having properties of economic, eco-friendly and high surface area. It drew to enhance the amount of drug loading in the carrier. Electrospinning technique is used to fabricate fibrous component by optimization condition obtained from previous mechanical properties experiments. Release experiment was carried out by the degree of dye absorbance at 544nm by ultraviolet–visible spectroscopy, the RhB in SiO2 alternative drug for modelling of drug release was released for 1 ~ 20 days at 37°C in phosphate buffer. Furthermore, the Mechanical property was confirmed by DSC, TGA. Morphology and degree of biodegradation were shown as SEM images and EDS.

Archaeosomes: an excellent carrier for drug and cell delivery.

Science.gov (United States)

Kaur, Gurmeet; Garg, Tarun; Rath, Goutam; Goyal, Amit K

2016-09-01

Archaeosomes as liposomes made with one or more ether lipids that are unique to the domain of Archaeobacteria, found in Archaea constitute a novel family of liposome. Achaean-type lipids consist of archaeol (diether) and/or caldarchaeol (tetraether) core structures. Archaeosomes can be produced using standard procedures (hydrated film submitted to sonication, extrusion and detergent dialysis) at any temperature in the physiological range or lower, therefore making it possible to encapsulate thermally stable compounds. Various physiological as well as environmental factors affect its stability. Archaeosomes are widely used as drug delivery systems for cancer vaccines, Chagas disease, proteins and peptides, gene delivery, antigen delivery and delivery of natural antioxidant compounds. In this review article, our major aim was to explore the applications of this new carrier system in pharmaceutical field.

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.

Role of self-assembly coated Er3+: YAlO3/TiO2 in intimate coupling of visible-light-responsive photocatalysis and biodegradation reactions

International Nuclear Information System (INIS)

Dong, Shanshan; Dong, Shuangshi; Tian, Xiadi; Xu, Zhengxue; Ma, Dongmei; Cui, Bin; Ren, Nanqi; Rittmann, Bruce E.

2016-01-01

Highlights: • First study on intimate coupling of photocatalysis & biodegradation by visible light. • Self-assembly was used to coat Er 3+ : YAlO 3 /TiO 2 on the sponge carriers. • Fewer accumulated intermediates & higher phenol removal for VPCB than VPC or B alone. • Self-regulation in VPCB contributes to the high degradation efficiency. - Abstract: Conventionally used ultraviolet light can result in dissolved organic carbon (DOC) increasing and biofilm damage in intimate coupling of photocatalysis and biodegradation (ICPB). Visible-light-responsive photocatalysis offers an alternative for achieving ICPB. In this study, composite-cubes were developed using self-assembly to coat a thin and even layer of visible-light-responsive photocatalyst (Er 3+ : YAlO 3 /TiO 2 ) on sponge-type carriers, followed by biofilm cultivation. The degradations of phenol (50 mg L −1 ) were compared for four protocols in circulating beds: adsorption (AD), visible-light-responsive photocatalysis (VPC), biodegradation (B), and intimately coupled visible-light-responsive photocatalysis and biodegradation (VPCB). The phenol and DOC removal efficiencies using VPCB in 16 h were 99.8% and 65.2%, respectively, i.e., higher than those achieved using VPC (71.6% and 50.0%) or B (99.4% and 58.2%). The phenol removal of 96.3% could be obtained even after 3 additional cycles. The 6.17-min intermediate detected by HPLC, continuously accumulated for VPC, appeared at 1–6 h and then was completely removed for VPCB in 10 h. ICPB was further illustrated in that most of the biofilm was protected in the carrier interiors, with less protection on the carrier exterior in VPCB. A self-regulation mechanism that helped photocatalyst exposure to visible-light irradiation was identified, promoting the combined photocatalysis and biodegradation.

pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms.

Science.gov (United States)

Liu, Lin; Yao, WenDong; Rao, YueFeng; Lu, XiaoYang; Gao, JianQing

2017-11-01

Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines. This review provides a wide perspective on current status of pH-responsive oral drug delivery systems prepared mainly with organic polymers or inorganic materials, including the strategies used to overcome GI barriers, the challenges in their development and future prospects, with focus on technology trends to improve the bioavailability of orally delivered drugs, the mechanisms of drug release from pH-responsive oral formulations, and their application for drug delivery, such as protein and peptide therapeutics, vaccination, inflammatory bowel disease (IBD) and bacterial infections.

Nanomembranes and Nanofibers from Biodegradable Conducting Polymers

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Jordi Puiggalí

2013-09-01

Full Text Available This review provides a current status report of the field concerning preparation of fibrous mats based on biodegradable (e.g., aliphatic polyesters such as polylactide or polycaprolactone and conducting polymers (e.g., polyaniline, polypirrole or polythiophenes. These materials have potential biomedical applications (e.g., tissue engineering or drug delivery systems and can be combined to get free-standing nanomembranes and nanofibers that retain the better properties of their corresponding individual components. Systems based on biodegradable and conducting polymers constitute nowadays one of the most promising solutions to develop advanced materials enable to cover aspects like local stimulation of desired tissue, time controlled drug release and stimulation of either the proliferation or differentiation of various cell types. The first sections of the review are focused on a general overview of conducting and biodegradable polymers most usually employed and the explanation of the most suitable techniques for preparing nanofibers and nanomembranes (i.e., electrospinning and spin coating. Following sections are organized according to the base conducting polymer (e.g., Sections 4–6 describe hybrid systems having aniline, pyrrole and thiophene units, respectively. Each one of these sections includes specific subsections dealing with applications in a nanofiber or nanomembrane form. Finally, miscellaneous systems and concluding remarks are given in the two last sections.

Biodegradable Polymers and Stem Cells for Bioprinting

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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.

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.

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.

Surface Modified Multifunctional and Stimuli Responsive Nanoparticles for Drug Targeting: Current Status and Uses

Directory of Open Access Journals (Sweden)

Panoraia I. Siafaka

2016-08-01

Full Text Available Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic–organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the “state of the art” of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined.

[Carrier-mediated Transport of Cationic Drugs across the Blood-Tissue Barrier].

Science.gov (United States)

Kubo, Yoshiyuki

2015-01-01

Studies of neurological dysfunction have revealed the neuroprotective effect of several cationic drugs, suggesting their usefulness in the treatment of neurological diseases. In the brain and retina, blood-tissue barriers such as blood-brain barrier (BBB) and blood-retinal barrier (BRB) are formed to restrict nonspecific solute transport between the circulating blood and neural tissues. Therefore study of cationic drug transport at these barriers is essential to achieve systemic delivery of neuroprotective agents into the neural tissues. In the retina, severe diseases such as diabetic retinopathy and macular degeneration can cause neurological dysfunction that dramatically affects patients' QOL. The BRB is formed by retinal capillary endothelial cells (inner BRB) and retinal pigment epithelial cells (outer BRB). Blood-to-retina transport of cationic drugs was investigated at the inner BRB, which is known to nourish two thirds of the retina. Blood-to-retinal transport of verapamil suggested that the barrier function of the BRB differs from that of the BBB. Moreover, carrier-mediated transport of verapamil and pyrilamine revealed the involvement of novel organic cation transporters at the inner BRB. The identified transport systems for cationic drugs are sensitive to several cationic neuroprotective and anti-angiogenic agents such as clonidine and propranolol, and the involvement of novel transporters was also suggested in their blood-to-retina transport across the inner BRB.

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.

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...

Effect of PEGylation on ligand-based targeting of drug carriers to the vascular wall in blood flow.

Science.gov (United States)

Onyskiw, Peter J; Eniola-Adefeso, Omolola

2013-09-03

The blood vessel wall plays a prominent role in the development of many life-threatening diseases and as such is an attractive target for treatment. To target diseased tissue, particulate drug carriers often have their surfaces modified with antibodies or epitopes specific to vascular wall-expressed molecules, along with poly(ethylene glycol) (PEG) to improve carrier blood circulation time. However, little is known about the effect of poly(ethylene glycol) on carrier adhesion dynamics-specifically in blood flow. Here we examine the influence of different molecular weight PEG spacers on particle adhesion in blood flow. Anti-ICAM-1 or Sialyl Lewis(a) were grafted onto polystyrene 2 μm and 500 nm spheres via PEG spacers and perfused in blood over activated endothelial cells at physiological shear conditions. PEG spacers were shown to improve, reduce, or have no effect on the binding density of targeted-carriers depending on the PEG surface conformation, shear rate, and targeting moiety.

Perspective highlights on biodegradable polymeric nanosystems for targeted therapy of solid tumors.

Science.gov (United States)

Fathi, Marziyeh; Barar, Jaleh

2017-01-01

Introduction: Polymeric nanoparticles (NPs) formulated using biodegradable polymers offer great potential for development of de novo drug delivery systems (DDSs) capable of delivering a wide range of bioactive agents. They can be engineered as advanced multifunctional nanosystems (NSs) for simultaneous imaging and therapy known as theranostics or diapeutics. Methods: A brief prospective is provided on biomedical importance and applications of biodegradable polymeric NSs through reviewing the recently published literature. Results: Biodegradable polymeric NPs present unique characteristics, including: nanoscaled structures, high encapsulation capacity, biocompatibility with non-thrombogenic and non-immunogenic properties, and controlled-/sustained-release profile for lipophilic and hydrophilic drugs. Once administered in vivo, all classes of biodegradable polymers (i.e., synthetic, semi-synthetic, and natural polymers) are subjected to enzymatic degradation; and hence, transformation into byproducts that can be simply eliminated from the human body. Natural and semi-synthetic polymers have been shown to be highly stable, much safer, and offer a non-/less-toxic means for specific delivery of cargo drugs in comparison with synthetic polymers. Despite being biocompatible and enzymatically-degradable, there are some drawbacks associated with these polymers such as batch to batch variation, high production cost, structural complexity, lower bioadhesive potential, uncontrolled rate of hydration, and possibility of microbial spoilage. These pitfalls have bolded the importance of synthetic counterparts despite their somewhat toxicity. Conclusion: Taken all, to minimize the inadvertent effects of these polymers and to engineer much safer NSs, it is necessary to devise biopolymers with desirable chemical and biochemical modification(s) and polyelectrolyte complex formation to improve their drug delivery capacity in vivo.

Unprecedented access to functional biodegradable polymers and coatings

NARCIS (Netherlands)

Lee, Jung Seok; Wang, Rong; Chen, Wei; Meng, Fenghua; Cheng, Ru; Deng, Chao; Feijen, Jan; Zhong, Zhiyuan

2011-01-01

The ever-growing biomedical technology such as tissue engineering, regenerative medicine, and controlled drug release intimately relies on the development of advanced functional biomaterials. Here, we report on versatile and robust synthesis of novel vinyl sulfone (VS)-functionalized biodegradable

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.

"Thunderstruck": Plasma-Polymer-Coated Porous Silicon Microparticles As a Controlled Drug Delivery System.

Science.gov (United States)

McInnes, Steven J P; Michl, Thomas D; Delalat, Bahman; Al-Bataineh, Sameer A; Coad, Bryan R; Vasilev, Krasimir; Griesser, Hans J; Voelcker, Nicolas H

2016-02-01

Controlling the release kinetics from a drug carrier is crucial to maintain a drug's therapeutic window. We report the use of biodegradable porous silicon microparticles (pSi MPs) loaded with the anticancer drug camphothecin, followed by a plasma polymer overcoating using a loudspeaker plasma reactor. Homogenous "Teflon-like" coatings were achieved by tumbling the particles by playing AC/DC's song "Thunderstruck". The overcoating resulted in a markedly slower release of the cytotoxic drug, and this effect correlated positively with the plasma polymer coating times, ranging from 2-fold up to more than 100-fold. Ultimately, upon characterizing and verifying pSi MP production, loading, and coating with analytical methods such as time-of-flight secondary ion mass spectrometry, scanning electron microscopy, thermal gravimetry, water contact angle measurements, and fluorescence microscopy, human neuroblastoma cells were challenged with pSi MPs in an in vitro assay, revealing a significant time delay in cell death onset.

Seaweed Polysaccharide-Based Nanoparticles: Preparation and Applications for Drug Delivery

Directory of Open Access Journals (Sweden)

Jayachandran Venkatesan

2016-01-01

Full Text Available In recent years, there have been major advances and increasing amounts of research on the utilization of natural polymeric materials as drug delivery vehicles due to their biocompatibility and biodegradability. Seaweed polysaccharides are abundant resources and have been extensively studied for several biological, biomedical, and functional food applications. The exploration of seaweed polysaccharides for drug delivery applications is still in its infancy. Alginate, carrageenan, fucoidan, ulvan, and laminarin are polysaccharides commonly isolated from seaweed. These natural polymers can be converted into nanoparticles (NPs by different types of methods, such as ionic gelation, emulsion, and polyelectrolyte complexing. Ionic gelation and polyelectrolyte complexing are commonly employed by adding cationic molecules to these anionic polymers to produce NPs of a desired shape, size, and charge. In the present review, we have discussed the preparation of seaweed polysaccharide-based NPs using different types of methods as well as their usage as carriers for the delivery of various therapeutic molecules (e.g., proteins, peptides, anti-cancer drugs, and antibiotics. Seaweed polysaccharide-based NPs exhibit suitable particle size, high drug encapsulation, and sustained drug release with high biocompatibility, thereby demonstrating their high potential for safe and efficient drug delivery.

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

Directory of Open Access Journals (Sweden)

Manjusha Rani

2010-11-01

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

Role of self-assembly coated Er{sup 3+}: YAlO{sub 3}/TiO{sub 2} in intimate coupling of visible-light-responsive photocatalysis and biodegradation reactions

Energy Technology Data Exchange (ETDEWEB)

Dong, Shanshan [Key Lab of Groundwater Resources and Environment, Ministry of Education, Jilin University, Changchun 130021 (China); Dong, Shuangshi, E-mail: dongshuangshi@gmail.com [Key Lab of Groundwater Resources and Environment, Ministry of Education, Jilin University, Changchun 130021 (China); Tian, Xiadi; Xu, Zhengxue; Ma, Dongmei; Cui, Bin [Key Lab of Groundwater Resources and Environment, Ministry of Education, Jilin University, Changchun 130021 (China); Ren, Nanqi, E-mail: rnq@hit.edu.cn [State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology (SKLUWRE, HIT), Harbin 150090 (China); Rittmann, Bruce E. [Swette Center for Environmetal Technology, Biodesign Institute at Arizona State University, Tempe, AZ, 85287-5701 (United States)

2016-01-25

Highlights: • First study on intimate coupling of photocatalysis & biodegradation by visible light. • Self-assembly was used to coat Er{sup 3+}: YAlO{sub 3}/TiO{sub 2} on the sponge carriers. • Fewer accumulated intermediates & higher phenol removal for VPCB than VPC or B alone. • Self-regulation in VPCB contributes to the high degradation efficiency. - Abstract: Conventionally used ultraviolet light can result in dissolved organic carbon (DOC) increasing and biofilm damage in intimate coupling of photocatalysis and biodegradation (ICPB). Visible-light-responsive photocatalysis offers an alternative for achieving ICPB. In this study, composite-cubes were developed using self-assembly to coat a thin and even layer of visible-light-responsive photocatalyst (Er{sup 3+}: YAlO{sub 3}/TiO{sub 2}) on sponge-type carriers, followed by biofilm cultivation. The degradations of phenol (50 mg L{sup −1}) were compared for four protocols in circulating beds: adsorption (AD), visible-light-responsive photocatalysis (VPC), biodegradation (B), and intimately coupled visible-light-responsive photocatalysis and biodegradation (VPCB). The phenol and DOC removal efficiencies using VPCB in 16 h were 99.8% and 65.2%, respectively, i.e., higher than those achieved using VPC (71.6% and 50.0%) or B (99.4% and 58.2%). The phenol removal of 96.3% could be obtained even after 3 additional cycles. The 6.17-min intermediate detected by HPLC, continuously accumulated for VPC, appeared at 1–6 h and then was completely removed for VPCB in 10 h. ICPB was further illustrated in that most of the biofilm was protected in the carrier interiors, with less protection on the carrier exterior in VPCB. A self-regulation mechanism that helped photocatalyst exposure to visible-light irradiation was identified, promoting the combined photocatalysis and biodegradation.

Plant lectins as carriers for oral drugs: Is wheat germ agglutinin a suitable candidate?

International Nuclear Information System (INIS)

Dalla Pellegrina, Chiara; Rizzi, Corrado; Mosconi, Silvia; Zoccatelli, Gianni; Peruffo, Angelo; Chignola, Roberto

2005-01-01

Wheat germ agglutinin (WGA) is a plant protein that binds specifically to sugars expressed also by gastrointestinal epithelial cells. WGA is currently investigated as an anti-tumor drug and as a carrier for oral drugs. Information on whether it can cross the gastrointestinal epithelium and on its possible effects on the integrity of the epithelial layer is however scanty or lacking, and herein we address these issues. Differentiated Caco2 cells have been used as a model of polarized intestinal epithelium. WGA concentration at both the apical and the basolateral side of the epithelium has been quantified using a sensitive ELISA assay (sensitivity threshold 0.84 nM). Trans epithelial electrical resistance (TEER) has been measured to evaluate the integrity of the epithelium upon treatments with WGA. 3 H-Mannitol (182.2 Da) and FITC-dextran (3000 Da) have been used to measure the permeability of the epithelium. Cell viability has been measured by the MTT, by 7-AAD uptake, and Annexin-V binding assays. Up to a concentration of 5.6 μM, ∼0.1% of intact WGA molecules only could cross the epithelial layer. WGA perturbed the integrity of the epithelium and increased the permeability of the tissue in a dose- and time-dependent manner. WGA did not induce cell death but increased the permeability of individual cells to 7-AAD which is normally not uptaken by viable cells. These data allowed us to define a toxicity threshold for WGA on epithelial cells. WGA suitability as a carrier for oral drugs can therefore be evaluated on a rational basis

Utilization of Waste Materials for Microbial Carrier in Wastewater Treatment

Directory of Open Access Journals (Sweden)

H. T. Le

2016-01-01

Full Text Available This research focused on the ammonium-nitrogen (NH4-N removal from the domestic wastewater using the attached growth reactors. Two types of waste material of corncob (biodegradable material and concrete (nonbiodegradable material were used as the carrier for microorganisms’ attachment. During operation, both reactors achieved absolutely high performance of ammonium removal (up to 99% and total nitrogen removal (up to 95%. The significant advantage of corncob carrier was that the corncob was able to be a source of carbon for biological denitrification, leading to no external carbon requirement for operating the system. However, the corncob caused an increasing turbidity of the effluent. On the other hand, the concrete carrier required the minimal external carbon of 3.5 C/N ratio to reach the good performance. Moreover, a longer period for microorganisms’ adaptation was found in the concrete carrier rather than the corncob carrier. Further, the same physiological and biochemical characteristics of active bacteria were found at the two carriers, which were negative gram, cocci shape, and smooth and white-turbid colony. Due to the effluent quality, the concrete was more appropriate carrier than the corncob for wastewater treatment.

Encapsulation of anticancer drug and magnetic particles in biodegradable polymer nanospheres

Energy Technology Data Exchange (ETDEWEB)

Koneracka, M; Zavisova, V; Tomasovicova, N; Kopcansky, P; Timko, M; JurIkova, A; Csach, K; Kavecansky, V; Lancz, G [Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, Kosice (Slovakia); Muckova, M [Hameln rds a.s., Horna 36, Modra (Slovakia)], E-mail: konerack@saske.sk

2008-05-21

In this study, we have prepared PLGA (poly-D,L-lactide-co-glycolide) nanospheres loaded with biocompatible magnetic fluid and anticancer drug taxol by a modified nanoprecipitation technique and investigated their magnetic properties. A magnetic fluid, MF-PEG, with a biocompatible layer of polyethylene glycol (PEG), was chosen as a magnetic carrier. The PLGA, whose copolymer ratio of D,L-lactide to glycolide is 85:15, was utilized as a capsulation material. Taxol, as an important anticancer drug, was chosen for its significant role against a wide range of tumours. The morphology and particle size distributions of the prepared nanospheres were investigated by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and showed a spherical shape of prepared nanospheres with size 250 nm. Infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetry (TGA) analysis confirmed incorporation of magnetic particles and taxol into the PLGA polymer. The results showed good encapsulation with magnetite content 21.5 wt% and taxol 0.5 wt%. Magnetic properties of magnetic fluids and taxol within the PLGA polymer matrix were investigated by SQUID magnetometry from 4.2 to 300 K. The SQUID measurements showed superparamagnetism of prepared nanospheres with a blocking temperature of 160 K and saturation magnetization 1.4 mT.

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.

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

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.

Aerobic biodegradation of a nonylphenol polyethoxylate and toxicity of the biodegradation metabolites.

Science.gov (United States)

Jurado, Encarnación; Fernández-Serrano, Mercedes; Núñez-Olea, Josefa; Lechuga, Manuela

2009-09-01

In this paper a study was made of the biodegradation of a non-ionic surfactant, a nonylphenol polyethoxylate, in biodegradability tests by monitoring the residual surfactant matter. The influence of the concentration on the extent of primary biodegradation, the toxicity of biodegradation metabolites, and the kinetics of degradation were also determined. The primary biodegradation was studied at different initial concentrations: 5, 25 and 50 mg/L, (at sub-and supra-critical micelle concentration). The NPEO used in this study can be considered biodegradable since the primary biodegradation had already taken place (a biodegradation greater than 80% was found for the different initial concentration tested). The initial concentration affected the shape of the resulting curve, the mean biodegradation rate and the percentage of biodegradation reached (99% in less than 8 days at 5 mg/L, 98% in less than 13 days at 25 mg/L and 95% in 14 days at 50 mg/L). The kinetic model of Quiroga and Sales (1991) was applied to predict the biodegradation of the NPEO. The toxicity value was measured as EC(20) and EC(50). In addition, during the biodegradation process of the surfactant a toxicity analysis was made of the evolution of metabolites generated, confirming that the subproducts of the biodegradation process were more toxic than the original.

Histidine-lysine peptides as carriers of nucleic acids.

Science.gov (United States)

Leng, Qixin; Goldgeier, Lisa; Zhu, Jingsong; Cambell, Patricia; Ambulos, Nicholas; Mixson, A James

2007-03-01

With their biodegradability and diversity of permutations, peptides have significant potential as carriers of nucleic acids. This review will focus on the sequence and branching patterns of peptide carriers composed primarily of histidines and lysines. While lysines within peptides are important for binding to the negatively charged phosphates, histidines are critical for endosomal lysis enabling nucleic acids to reach the cytosol. Histidine-lysine (HK) polymers by either covalent or ionic bonds with liposomes augment transfection compared to liposome carriers alone. More recently, we have examined peptides as sole carriers of nucleic acids because of their intrinsic advantages compared to the bipartite HK/liposome carriers. With a protocol change and addition of a histidine-rich tail, HK peptides as sole carriers were more effective than liposomes alone in several cell lines. While four-branched polymers with a primary repeating sequence pattern of -HHK- were more effective as carriers of plasmids, eight-branched polymers with a sequence pattern of -HHHK- were more effective as carriers of siRNA. Compared to polyethylenimine, HK carriers of siRNA and plasmids had reduced toxicity. When injected intravenously, HK polymers in complex with plasmids encoding antiangiogenic proteins significantly decreased tumor growth. Furthermore, modification of HK polymers with polyethylene glycol and vascular-specific ligands increased specificity of the polyplex to the tumor by more than 40-fold. Together with further development and insight on the structure of HK polyplexes, HK peptides may prove to be useful as carriers of different forms of nucleic acids both in vitro and in vivo.

N-succinyl-chitosan as a drug carrier: water-insoluble and water-soluble conjugates.

Science.gov (United States)

Kato, Yoshinori; Onishi, Hiraku; Machida, Yoshiharu

2004-02-01

N-succinyl-chitosan (Suc-Chi) has favourable properties as a drug carrier such as biocompatibility, low toxicity and long-term retention in the body. It was long retained in the systemic circulation after intravenous administration, and the plasma half-lives of Suc-Chi (MW: 3.4 x 10(5); succinylation degree: 0.81 mol/sugar unit; deacetylation degree: 1.0 mol/sugar unit) were ca. 100.3h in normal mice and 43 h in Sarcoma 180-bearing mice. The biodistribution of Suc-Chi into other tissues was trace apart from the prostate and lymph nodes. The maximum tolerable dose for the intraperitoneal injection of Suc-Chi to mice was greater than 2 g/kg. The water-insoluble and water-soluble conjugates could be prepared using a water-soluble carbodiimide and mitomycin C (MMC) or using an activated ester of glutaric MMC. In vitro release characteristics of these conjugates showed similar patterns, i.e. a pH-dependent manner, except that water-insoluble conjugates showed a slightly slower release of MMC than water-soluble ones. The conjugates of MMC with Suc-Chi showed good antitumour activities against various tumours such as murine leukaemias (L1210 and P388), B16 melanoma, Sarcoma 180 solid tumour, a murine liver metastatic tumour (M5076) and a murine hepatic cell carcinoma (MH134). This review summarizes the utilization of Suc-Chi as a drug carrier for macromolecular conjugates of MMC and the therapeutic efficacy of the conjugates against various tumours.

Impact of Pore–Walls Ligand Assembly on the Biodegradation of Mesoporous Organosilica Nanoparticles for Controlled Drug Delivery

KAUST Repository

Omar, Haneen

2018-05-14

Porous materials with molecular-scale ordering have attracted major attention mainly because of the possibility to engineer their pores for selective applications. Periodic mesoporous organosilica is a class of hybrid materials where self-assembly of the organic linkers provides a crystal-like pore wall. However, unlike metal coordination, specific geometries cannot be predicted because of the competitive and dynamic nature of noncovalent interactions. Herein, we study the influence of competing noncovalent interactions in the pore walls on the biodegradation of organosilica frameworks for drug delivery application. These results support the importance of studying self-assembly patterns in hybrid frameworks to better engineer the next generation of dynamic or “soft” porous materials.

Biodegradability and biodegradation rate of poly(caprolactone)-starch blend and poly(butylene succinate) biodegradable polymer under aerobic and anaerobic environment.

Science.gov (United States)

Cho, H S; Moon, H S; Kim, M; Nam, K; Kim, J Y

2011-03-01

The biodegradability and the biodegradation rate of two kinds biodegradable polymers; poly(caprolactone) (PCL)-starch blend and poly(butylene succinate) (PBS), were investigated under both aerobic and anaerobic conditions. PCL-starch blend was easily degraded, with 88% biodegradability in 44 days under aerobic conditions, and showed a biodegradation rate of 0.07 day(-1), whereas the biodegradability of PBS was only 31% in 80 days under the same conditions, with a biodegradation rate of 0.01 day(-1). Anaerobic bacteria degraded well PCL-starch blend (i.e., 83% biodegradability for 139 days); however, its biodegradation rate was relatively slow (6.1 mL CH(4)/g-VS day) compared to that of cellulose (13.5 mL CH(4)/g-VS day), which was used as a reference material. The PBS was barely degraded under anaerobic conditions, with only 2% biodegradability in 100 days. These results were consistent with the visual changes and FE-SEM images of the two biodegradable polymers after the landfill burial test, showing that only PCL-starch blend had various sized pinholes on the surface due to attack by microorganisms. This result may be use in deciding suitable final disposal approaches of different types of biodegradable polymers in the future. Copyright © 2010 Elsevier Ltd. All rights reserved.

Proceedings of biodegradation

International Nuclear Information System (INIS)

Anon.

1990-01-01

This book contains the proceedings of Biodegradation. Topics include:biodegradation using the tools of biotechnology, basic science aspects of biodegradation, the physiological characteristics of microorganisms, the use of selective techniques that enhance the process of microbial evolution of biodegradative genes in nature, the genetic characteristics of microorganisms allowing them to biodegrade both natural and synthetic toxic chemicals, the molecular techniques that allow selective assembly of genetic segments form a variety of bacterial strains to a single strain, and methods needed to advance biodegradation research as well as the high-priority chemical problems important to the Department of Defense or to the chemical industry

Investigation of interaction of vanillin with Alpha, Beta and Gamma-cyclodextrin as drug delivery carriers: brief report

Directory of Open Access Journals (Sweden)

Batoolalsadat Mousavi Fard

2015-05-01

Methods: All theoretical calculations were performed on a Intel® Core™ i5 Processors computer at Kerman University using Gaussian 09 program package (Gaussian, Inc., Wallingford, USA in a three month period (February 2014 to May 2014. Starting geometries were generated employing GaussView software, version 5 (Gaussian, Inc., Wallingford, USA and then the resulting coordinates were optimized using density functional theory (DFT calculations. The natural bond orbital method (NBO program, under Gaussian 09 program package was carried out to study charge transfer energy associated with the intermolecular interactions. The quantum theory of atoms in molecules was applied for DFT results to get insight in the nature of interaction existing in the investigated systems. The calculations were carried out with AIM2000 program and AIMAll 14.10.27 package (Todd A. Keith, TK Gristmill software, Overland Park KS, USA to find and characterize bond critical points. Results: The vanillin molecule is adsorbed on the surface of carriers by hydrogen bonding between its oxygen atom and hydrogen atoms of cyclodextrin. The hydrogen of -OH group on the cyclodextrin can form hydrogen bond to the oxygen atom of carbonyl group of vanillin molecule. This study indicates a decrease of total energy with increasing surface of cyclodextrin. So gamma-cyclodextrin and its complex with the maximum surface in between carriers have the highest stabilities. The gamma-cyclodextrin shows the strongest interaction with vanillin. In all complexes of vanillin-cyclodextrin, the direction of charge transfer is from drug to carrier. Conclusion: Due to the high solubility of gamma-cyclodxtrin and its stronger interaction with the molecule vanillin, it can be the best option as drug carrier.

Peptide and protein delivery using new drug delivery systems.

Science.gov (United States)

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

2013-01-01

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

Enhancement of aerobic biodegradation in an oxygen-limiting environment using a saponin-based microbubble suspension

International Nuclear Information System (INIS)

Choi, Yong Ju; Kim, Young-Jin; Nam, Kyoungphile

2009-01-01

This study investigated the ability of a saponin-based microbubble suspension to enhance aerobic biodegradation of phenanthrene by subsurface delivery. As the microbubble suspension flowed through a sand column pressure buildup and release was repeatedly observed, which delivered oxygen to the less permeable regions. Burkholderia cepacia RPH1, a phenanthrene-degrading bacterium, was mainly transported in a suspended form in the microbubble suspension. When three pore volumes of the microbubble suspension containing B. cepacia RPH1 was introduced into a column contaminated with phenanthrene (100 mg/kg), the oxygen content declined to 5% from an initial value of 20% within 5 days and correspondingly, 34.4% of initial phenanthrene was removed in 8 days. The addition of two further three pore volumes enhanced the biodegradation efficiency by a factor of 2.2. Our data suggest that a saponin-based microbubble suspension could be a potential carrier for enhancing the aerobic biodegradation under an oxygen-limiting environment. - Microbubble suspension can enhance the phenanthrene biodegradation under an oxygen-limiting condition.

Enhancement of aerobic biodegradation in an oxygen-limiting environment using a saponin-based microbubble suspension

Energy Technology Data Exchange (ETDEWEB)

Choi, Yong Ju; Kim, Young-Jin [Department of Civil and Environmental Engineering, Seoul National University, Shillim-dong, Gwanak-gu, Seoul (Korea, Republic of); Nam, Kyoungphile, E-mail: kpnam@snu.ac.k [Department of Civil and Environmental Engineering, Seoul National University, Shillim-dong, Gwanak-gu, Seoul (Korea, Republic of)

2009-08-15

This study investigated the ability of a saponin-based microbubble suspension to enhance aerobic biodegradation of phenanthrene by subsurface delivery. As the microbubble suspension flowed through a sand column pressure buildup and release was repeatedly observed, which delivered oxygen to the less permeable regions. Burkholderia cepacia RPH1, a phenanthrene-degrading bacterium, was mainly transported in a suspended form in the microbubble suspension. When three pore volumes of the microbubble suspension containing B. cepacia RPH1 was introduced into a column contaminated with phenanthrene (100 mg/kg), the oxygen content declined to 5% from an initial value of 20% within 5 days and correspondingly, 34.4% of initial phenanthrene was removed in 8 days. The addition of two further three pore volumes enhanced the biodegradation efficiency by a factor of 2.2. Our data suggest that a saponin-based microbubble suspension could be a potential carrier for enhancing the aerobic biodegradation under an oxygen-limiting environment. - Microbubble suspension can enhance the phenanthrene biodegradation under an oxygen-limiting condition.

Biodegradable polyurethane nanocomposites containing dexamethasone for ocular route

Energy Technology Data Exchange (ETDEWEB)

Rodrigues da Silva, Gisele [Federal University of Sao Joao Del Rei, School of Pharmacy, Divinopolis, Minas Gerais (Brazil); Silva-Cunha, Armando da [Federal University of Minas Gerais, School of Pharmacy, Belo Horizonte, Minas Gerais (Brazil); Behar-Cohen, Francine [INSERM, Physiopathology of ocular diseases: Therapeutic innovations, Institut des Cordeliers, Paris (France); Laboratoire d' Innovations Therapeutiques, Fondation Rothschild, Paris (France); Universite Rene Descartes, Hotel Dieu University Hospital, Paris (France); Ayres, Eliane [Federal University of Minas Gerais, Department of Metallurgical and Materials Engineering, Belo Horizonte, Minas Gerais (Brazil); Orefice, Rodrigo L., E-mail: rorefice@demet.ufmg.br [Federal University of Minas Gerais, Department of Metallurgical and Materials Engineering, Belo Horizonte, Minas Gerais (Brazil)

2011-03-12

The treatment of posterior segment ocular diseases, such as uveitis, by using eye drops and oral drugs is usually not effective due to the body's natural barriers to drug penetration. In this study, ocular implants to treat uveitis were synthesized by incorporating dexamethasone acetate, an important type of corticoid used in the treatment of some uveitis, into a biodegradable polyurethane containi clay nanoparticles. Biodegradable polyurethane nanocomposites having poly(caprolactone) oligomers as soft segments were obtained by delaminating clay particles within a polyurethane aqueous dispersion. The drug was incorporated into the polymer by dispersing it in the waterborne polyurethane followed by a drying step. Nanoparticles derived from clay were demonstrated to be able to tailor the mechanical properties of polyurethanes to achieve values that can match the properties of ocular soft tissues. Infrared spectra (FTIR) showed that the presence of clay particles was able to change the microphase separation process typical of polyurethanes. X-ray diffraction and small angle x-ray scattering (SAXS) results were explored to show that the incorporation of both dexamethasone acetate and nanocomponents derived from clay led to a less defined two-phase polyurethane. The presence of clay nanoparticles increased the rate of drug release measured in vitro. Human retinal pigment epithelial cells (ARPE-19) were cultured in contact with polyurethanes and polyurethane nanocomposites, and the viability of them (evaluated by using MTT assay after 7 days) showed that no toxic components were released from polyurethanes containing no drugs during the test.

Biodegradable polyurethane nanocomposites containing dexamethasone for ocular route

International Nuclear Information System (INIS)

Rodrigues da Silva, Gisele; Silva-Cunha, Armando da; Behar-Cohen, Francine; Ayres, Eliane; Orefice, Rodrigo L.

2011-01-01

The treatment of posterior segment ocular diseases, such as uveitis, by using eye drops and oral drugs is usually not effective due to the body's natural barriers to drug penetration. In this study, ocular implants to treat uveitis were synthesized by incorporating dexamethasone acetate, an important type of corticoid used in the treatment of some uveitis, into a biodegradable polyurethane containi clay nanoparticles. Biodegradable polyurethane nanocomposites having poly(caprolactone) oligomers as soft segments were obtained by delaminating clay particles within a polyurethane aqueous dispersion. The drug was incorporated into the polymer by dispersing it in the waterborne polyurethane followed by a drying step. Nanoparticles derived from clay were demonstrated to be able to tailor the mechanical properties of polyurethanes to achieve values that can match the properties of ocular soft tissues. Infrared spectra (FTIR) showed that the presence of clay particles was able to change the microphase separation process typical of polyurethanes. X-ray diffraction and small angle x-ray scattering (SAXS) results were explored to show that the incorporation of both dexamethasone acetate and nanocomponents derived from clay led to a less defined two-phase polyurethane. The presence of clay nanoparticles increased the rate of drug release measured in vitro. Human retinal pigment epithelial cells (ARPE-19) were cultured in contact with polyurethanes and polyurethane nanocomposites, and the viability of them (evaluated by using MTT assay after 7 days) showed that no toxic components were released from polyurethanes containing no drugs during the test.

Biodegradable, elastomeric coatings with controlled anti-proliferative agent release for magnesium-based cardiovascular stents.

Science.gov (United States)

Gu, Xinzhu; Mao, Zhongwei; Ye, Sang-Ho; Koo, Youngmi; Yun, Yeoheung; Tiasha, Tarannum R; Shanov, Vesselin; Wagner, William R

2016-08-01

Vascular stent design continues to evolve to further improve the efficacy and minimize the risks associated with these devices. Drug-eluting coatings have been widely adopted and, more recently, biodegradable stents have been the focus of extensive evaluation. In this report, biodegradable elastomeric polyurethanes were synthesized and applied as drug-eluting coatings for a relatively new class of degradable vascular stents based on Mg. The dynamic degradation behavior, hemocompatibility and drug release were investigated for poly(carbonate urethane) urea (PCUU) and poly(ester urethane) urea (PEUU) coated magnesium alloy (AZ31) stents. Poly(lactic-co-glycolic acid) (PLGA) coated and bare stents were employed as control groups. The PCUU coating effectively slowed the Mg alloy corrosion in dynamic degradation testing compared to PEUU-coated, PLGA-coated and bare Mg alloy stents. This was confirmed by electron microscopy, energy-dispersive x-ray spectroscopy and magnesium ion release experiments. PCUU-coating of AZ31 was also associated with significantly reduced platelet adhesion in acute blood contact testing. Rat vascular smooth muscle cell (rSMC) proliferation was successfully inhibited when paclitaxel was released from pre-loaded PCUU coatings. The corrosion retardation, low thrombogenicity, drug loading capacity, and high elasticity make PCUU an attractive option for drug eluting coating on biodegradable metallic cardiovascular stents. Copyright © 2016 Elsevier B.V. All rights reserved.

Liposomal Tumor Targeting in Drug Delivery Utilizing MMP-2- and MMP-9-Binding Ligands

Directory of Open Access Journals (Sweden)

Oula Penate Medina

2011-01-01

Full Text Available Nanotechnology offers an alternative to conventional treatment options by enabling different drug delivery and controlled-release delivery strategies. Liposomes being especially biodegradable and in most cases essentially nontoxic offer a versatile platform for several different delivery approaches that can potentially enhance the delivery and targeting of therapies to tumors. Liposomes penetrate tumors spontaneously as a result of fenestrated blood vessels within tumors, leading to known enhanced permeability and subsequent drug retention effects. In addition, liposomes can be used to carry radioactive moieties, such as radiotracers, which can be bound at multiple locations within liposomes, making them attractive carriers for molecular imaging applications. Phage display is a technique that can deliver various high-affinity and selectivity peptides to different targets. In this study, gelatinase-binding peptides, found by phage display, were attached to liposomes by covalent peptide-PEG-PE anchor creating a targeted drug delivery vehicle. Gelatinases as extracellular targets for tumor targeting offer a viable alternative for tumor targeting. Our findings show that targeted drug delivery is more efficient than non-targeted drug delivery.

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.

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)

Poly(glycerol adipate)-fatty acid esters as versatile nanocarriers

DEFF Research Database (Denmark)

Weiss, Verena M; Naolou, Toufik; Hause, Gerd

2012-01-01

Poly(glycerol adipate) (PGA) is a biodegradable polymer with promising features for nanoparticulate drug carrier systems. By acylation of PGA with fatty acids, composite systems with amphiphilic properties can be obtained. Variation of the fatty acid (laurate, stearate and behenate) and their sub...... and the nanoparticles. With their diverse particle shapes and internal structures as well as their different thermal behavior, aggregate states and polarities, the systems offer promising possibilities as delivery systems for lipophilic, amphiphilic and water soluble drugs.......Poly(glycerol adipate) (PGA) is a biodegradable polymer with promising features for nanoparticulate drug carrier systems. By acylation of PGA with fatty acids, composite systems with amphiphilic properties can be obtained. Variation of the fatty acid (laurate, stearate and behenate...

Predicting ready biodegradability of premanufacture notice chemicals.

Science.gov (United States)

Boethling, Robert S; Lynch, David G; Thom, Gary C

2003-04-01

Chemical substances other than pesticides, drugs, and food additives are regulated by the U.S. Environmental Protection Agency (U.S. EPA) under the Toxic Substances Control Act (TSCA), but the United States does not require that new substances be tested automatically for such critical properties as biodegradability. The resulting lack of submitted data has fostered the development of estimation methods, and the BioWIN models for predicting biodegradability from chemical structure have played a prominent role in premanufacture notice (PMN) review. Until now, validation efforts have used only the Japanese Ministry of International Trade and Industry (MITI) test data and have not included all models. To assess BioWIN performance with PMN substances, we assembled a database of PMNs for which ready biodegradation data had been submitted over the period 1995 through 2001. The 305 PMN structures are highly varied and pose major challenges to chemical property estimation. Despite the variability of ready biodegradation tests, the use of at least six different test methods, and widely varying quality of submitted data, accuracy of four of six BioWIN models (MITI linear, MITI nonlinear, survey ultimate, survey primary) was in the 80+% range for predicting ready biodegradability. Greater accuracy (>90%) can be achieved by using model estimates only when the four models agree (true for 3/4 of the PMNs). The BioWIN linear and nonlinear probability models did not perform as well even when classification criteria were optimized. The results suggest that the MITI and survey BioWIN models are suitable for use in screening-level applications.

Sustained delivery of biomolecules from gelatin carriers for applications in bone regeneration.

Science.gov (United States)

Song, Jiankang; Leeuwenburgh, Sander Cg

2014-08-01

Local delivery of therapeutic biomolecules to stimulate bone regeneration has matured considerably during the past decades, but control over the release of these biomolecules still remains a major challenge. To this end, suitable carriers that allow for tunable spatial and temporal delivery of biomolecules need to be developed. Gelatin is one of the most widely used natural polymers for the controlled and sustained delivery of biomolecules because of its biodegradability, biocompatibility, biosafety and cost-effectiveness. The current study reviews the applications of gelatin as carriers in form of bulk hydrogels, microspheres, nanospheres, colloidal gels and composites for the programmed delivery of commonly used biomolecules for applications in bone regeneration with a specific focus on the relationship between carrier properties and delivery characteristics.

Enhanced bioremediation of PAH-contaminated soil by immobilized bacteria with plant residue and biochar as carriers

Energy Technology Data Exchange (ETDEWEB)

Chen, Baoliang; Yuan, Miaoxin; Qian, Linbo [Zhejiang Univ., Hangzhou (China). Dept. of Environmental Science; Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou (China)

2012-10-15

Polycyclic aromatic hydrocarbons (PAHs) are largely accumulated in soils in China. The immobilized-microorganism technique (IMT) is a potential approach for abating soil contamination with PAHs. However, few studies about the application of IMT to contaminated soil remediation were reported. Due to recalcitrance to decomposition, biochar application to soil may enhance soil carbon sequestration, but few studies on the application of biochars to remediation of contaminated soil were reported. In this study, we illustrated enhanced bioremediation of soil having a long history of PAH contamination by IMT using plant residues and biochars as carriers. Two PAH-degrading bacteria, Pseudomonas putida and an unidentified indigenous bacterium, were selected for IMT. The extractability and biodegradation of 15 PAHs in solution and an actual PAH-contaminated soil amended with immobilized-bacteria materials were investigated under different incubation periods. The effects of carriers and the molecular weight of PAHs on bioremediation efficiency were determined to illustrate their different bio-dissipation mechanisms of PAHs in soil. The IMT can considerably enhance the removal of PAHs. Carriers impose different effects on PAH bio-dissipation by amended soil with immobilized-bacteria, which can directly degrade the carrier-associated PAHs. The removal of PAHs from soil depended on PAH molecular weight and carrier types. Enhanced bio-dissipation by IMT was much stronger for 4- and 5-ring PAHs than for 3- and 6-ring ones in soil. Only P400 biochar-immobilized bacteria enhanced bio-dissipation of all PAHs in contaminated soil after a 90-day incubation. Biochar can promote bioremediation of contaminated soil as microbial carriers of IMT. It is vital to select an appropriate biochar as an immobilized carrier to stimulate biodegradation. It is feasible to use adsorption carriers with high sorptive capabilities to concentrate PAHs as well as microorganisms and thereby enhance

Poly(trimethylene carbonate) as an elastic biodegradable film for human embryonic stem cell-derived retinal pigment epithelial cells

NARCIS (Netherlands)

Sorkio, Anni; Haimi, Suvi; Verdoold, Vincent; Juuti-Uusitalo, Kati; Grijpma, Dirk; Skottman, Heli

2017-01-01

Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cell therapies show tremendous potential for the treatment of retinal degenerative diseases. A tissue engineering approach, where cells are delivered to the subretinal space on a biodegradable carrier as a sheet, shows great

Poly(trimethylene carbonate) as an elastic biodegradable film for human embryonic stem cell-derived retinal pigment epithelial cells

NARCIS (Netherlands)

Sorkio, Anni; Haimi, Suvi; Verdoold, Vincent; Juuti-Uusitalo, Kati; Grijpma, Dirk; Skottman, Heli

Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cell therapies show tremendous potential for the treatment of retinal degenerative diseases. A tissue engineering approach, where cells are delivered to the subretinal space on a biodegradable carrier as a sheet, shows great

Nanovesicles released by Dictyostelium cells: a potential carrier for drug delivery.

Science.gov (United States)

Lavialle, Françoise; Deshayes, Sophie; Gonnet, Florence; Larquet, Eric; Kruglik, Sergei G; Boisset, Nicolas; Daniel, Régis; Alfsen, Annette; Tatischeff, Irène

2009-10-01

Nanovesicles released by Dictyostelium discoideum cells grown in the presence of the DNA-specific dye Hoechst 33342 have been previously shown to mediate the transfer of the dye into the nuclei of Hoechst-resistant cells. The present investigation extends this work by conducting experiments in the presence of hypericin, a fluorescent therapeutic photosensitizer assayed for antitumoral photodynamic therapy. Nanovesicles released by Dictyostelium cells exhibit an averaged diameter between 50 and 150 nm, as measured by transmission cryoelectron microscopy. A proteomic analysis reveals a predominance of actin and actin-related proteins. The detection of a lysosomal membrane protein (LIMP II) indicates that these vesicles are likely generated in the late endosomal compartment. The use of the hypericin-containing nanovesicles as nanodevices for in vitro drug delivery was investigated by fluorescence microscopy. The observed signal was almost exclusively located in the perinuclear area of two human cell lines, skin fibroblasts (HS68) and cervix carcinoma (HeLa) cells. Studies by confocal microscopy with specific markers of cell organelles, provided evidence that hypericin was accumulated in the Golgi apparatus. All these data shed a new light on in vitro drug delivery by using cell-released vesicles as carriers.

Biodegradable plastic bags on the seafloor: A future threat for seagrass meadows?

Science.gov (United States)

Balestri, Elena; Menicagli, Virginia; Vallerini, Flavia; Lardicci, Claudio

2017-12-15

Marine plastic litter is a global concern. Carrier bags manufactured from non-biodegradable polymers constitute a large component of this litter. Because of their adverse impact on marine life, non-biodegradable bags have recently been replaced by biodegradable ones. However, growing evidence shows that these latter are not readily degradable in marine sediments and can alter benthic assemblages. The potential impact of biodegradable bags on seagrasses inhabiting sandy bottoms, which are the most widespread and productive ecosystems of the coastal zones, has been ignored. Mesocosm experiments were conducted to assess the effect of a commercialized biodegradable bag on a common seagrass species of the Mediterranean, Cymodocea nodosa, both at the level of individual plant (clonal growth) and of plant community (plant-plant relationships), under three culture regimes (plant alone, in combination with a neighbour of the same species or of the co-existing seagrass Zostera noltei) simulating different natural conditions (bare substrate, monospecific meadows or mixed meadows). The bag behaviour in marine sediment and sediment physical/chemical variables were also examined. After six months of sediment exposure, the bag retained considerable mass (85% initial weight) and reduced sediment pore-water oxygen concentration and pH. In the presence of bag, C. nodosa root spread and vegetative recruitment increased compared to controls, both intra- and interspecific interactions shifted from neutral to competitive, and the growth form changed from guerrilla (loosely arranged group of widely spaced ramets) to phalanx form (compact structure of closed spaced ramets) but only with Z. noltei. These findings suggest that biodegradable bags altering sediment geochemistry could promote the spatial segregation of seagrass clones and influence species coexistence. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2017-11-01

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

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.

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

Science.gov (United States)

Ahmad, Muhammad; Liu, Sitong; Mahmood, Nasir; Mahmood, Asif; Ali, Muhammad; Zheng, Maosheng; Ni, Jinren

2017-04-19

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 -1 (98%) NH 4 , 311 mg L -1 (99%) NO 2 , and 633 mg L -1 (97%) total nitrogen (8 mg L -1 averaged NO 3 concentration was recorded in the effluent), accompanied by an efficient removal of chemical oxygen demand by 3286 mg L -1 (98%) and 350 mg L -1 (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.

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. ...

Organic solute carrier 22 (SLC22 family: Potential for interactions with food, herbal/dietary supplements, endogenous compounds, and drugs

Directory of Open Access Journals (Sweden)

Raymond E. Lai

2018-04-01

Full Text Available Many drugs, hormones, components of herbal medicines, environmental pesticides and toxins are Solute Carrier family 22 (SLC22 substrates. The last twenty years has seen great progress in determining SLC22 tissue expression profiles, membrane localization, energetics, substrate profiles and biopharmaceutical significance. However, much still remains to be answered in terms of SLC22 family member's roles in ‘normal’ physiology as compared to pathophysiological states, as well as in drug interactions that impact pharmacokinetics, efficacy and toxicity. This review begins with a brief synopsis of SLC22 family discovery, function and tissue expression. Subsequent sections provide examples establishing a role for SLC22 transporters in food-drug, herbal supplement-drug, endogenous substrate-drug and drug–drug interactions. Keywords: Hepatic transport, Nephrotoxicity, Organic anion transporter, Organic cation transporter, Renal transport

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

Intimately coupling of photolysis accelerates nitrobenzene biodegradation, but sequential coupling slows biodegradation

Energy Technology Data Exchange (ETDEWEB)

Yang, Lihui [Department of Environmental Science and Engineering, College of Life and Environmental Science, Shanghai Normal University, Shanghai 200234 (China); Zhang, Yongming, E-mail: zhym@shnu.edu.cn [Department of Environmental Science and Engineering, College of Life and Environmental Science, Shanghai Normal University, Shanghai 200234 (China); Bai, Qi; Yan, Ning; Xu, Hua [Department of Environmental Science and Engineering, College of Life and Environmental Science, Shanghai Normal University, Shanghai 200234 (China); Rittmann, Bruce E. [Swette Center for Environmental Biotechnology, Biodesign Institute, Arizona State University, Tempe, AZ 85287-5701 (United States)

2015-04-28

Highlights: • Intimately coupled UV photolysis accelerated nitrobenzene biodegradation. • NB biodegradation was slowed by accumulation of nitrophenol. • Oxalic acid was a key product of UV photolysis. • Oxalic acid accelerated biodegradation of nitrobenzene and nitrophenol by a co-substrate effect. • Intimate coupling of UV and biodegradation accentuated the benefits of oxalic acid. - Abstract: Photo(cata)lysis coupled with biodegradation is superior to photo(cata)lysis or biodegradation alone for removal of recalcitrant organic compounds. The two steps can be carried out sequentially or simultaneously via intimate coupling. We studied nitrobenzene (NB) removal and mineralization to evaluate why intimate coupling of photolysis with biodegradation was superior to sequential coupling. Employing an internal circulation baffled biofilm reactor, we compared direct biodegradation (B), biodegradation after photolysis (P + B), simultaneous photolysis and biodegradation (P&B), and biodegradation with nitrophenol (NP) and oxalic acid (OA) added individually and simultaneously (B + NP, B + OA, and B + NP + OA); NP and OA were NB’s main UV-photolysis products. Compared with B, the biodegradation rate P + B was lower by 13–29%, but intimately coupling (P&B) had a removal rate that was 10–13% higher; mineralization showed similar trends. B + OA gave results similar to P&B, B + NP gave results similar to P + B, and B + OA + NP gave results between P + B and P&B, depending on the amount of OA and NP added. The photolysis product OA accelerated NB biodegradation through a co-substrate effect, but NP was inhibitory. Although decreasing the UV photolysis time could minimize the inhibition impact of NP in P + B, P&B gave the fastest removal of NB by accentuating the co-substrate effect of OA.

Intimately coupling of photolysis accelerates nitrobenzene biodegradation, but sequential coupling slows biodegradation

International Nuclear Information System (INIS)

Yang, Lihui; Zhang, Yongming; Bai, Qi; Yan, Ning; Xu, Hua; Rittmann, Bruce E.

2015-01-01

Highlights: • Intimately coupled UV photolysis accelerated nitrobenzene biodegradation. • NB biodegradation was slowed by accumulation of nitrophenol. • Oxalic acid was a key product of UV photolysis. • Oxalic acid accelerated biodegradation of nitrobenzene and nitrophenol by a co-substrate effect. • Intimate coupling of UV and biodegradation accentuated the benefits of oxalic acid. - Abstract: Photo(cata)lysis coupled with biodegradation is superior to photo(cata)lysis or biodegradation alone for removal of recalcitrant organic compounds. The two steps can be carried out sequentially or simultaneously via intimate coupling. We studied nitrobenzene (NB) removal and mineralization to evaluate why intimate coupling of photolysis with biodegradation was superior to sequential coupling. Employing an internal circulation baffled biofilm reactor, we compared direct biodegradation (B), biodegradation after photolysis (P + B), simultaneous photolysis and biodegradation (P&B), and biodegradation with nitrophenol (NP) and oxalic acid (OA) added individually and simultaneously (B + NP, B + OA, and B + NP + OA); NP and OA were NB’s main UV-photolysis products. Compared with B, the biodegradation rate P + B was lower by 13–29%, but intimately coupling (P&B) had a removal rate that was 10–13% higher; mineralization showed similar trends. B + OA gave results similar to P&B, B + NP gave results similar to P + B, and B + OA + NP gave results between P + B and P&B, depending on the amount of OA and NP added. The photolysis product OA accelerated NB biodegradation through a co-substrate effect, but NP was inhibitory. Although decreasing the UV photolysis time could minimize the inhibition impact of NP in P + B, P&B gave the fastest removal of NB by accentuating the co-substrate effect of OA

Microbial colonization and degradation of polyethylene and biodegradable plastic bags in temperate fine-grained organic-rich marine sediments.

Science.gov (United States)

Nauendorf, Alice; Krause, Stefan; Bigalke, Nikolaus K; Gorb, Elena V; Gorb, Stanislav N; Haeckel, Matthias; Wahl, Martin; Treude, Tina

2016-02-15

To date, the longevity of plastic litter at the sea floor is poorly constrained. The present study compares colonization and biodegradation of plastic bags by aerobic and anaerobic benthic microbes in temperate fine-grained organic-rich marine sediments. Samples of polyethylene and biodegradable plastic carrier bags were incubated in natural oxic and anoxic sediments from Eckernförde Bay (Western Baltic Sea) for 98 days. Analyses included (1) microbial colonization rates on the bags, (2) examination of the surface structure, wettability, and chemistry, and (3) mass loss of the samples during incubation. On average, biodegradable plastic bags were colonized five times higher by aerobic and eight times higher by anaerobic microbes than polyethylene bags. Both types of bags showed no sign of biodegradation during this study. Therefore, marine sediment in temperate coastal zones may represent a long-term sink for plastic litter and also supposedly compostable material. Copyright © 2016 Elsevier Ltd. All rights reserved.

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......-coated sirolimus-eluting stent in a population-based setting....

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.

Calcium carbonate microspheres as carriers for the anticancer drug camptothecin

Energy Technology Data Exchange (ETDEWEB)

Qiu, Neng [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu ,610065 (China); Yin, Huabing, E-mail: huabing.yin@glasgow.ac.uk [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); Ji, Bozhi; Klauke, Norbert; Glidle, Andrew [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); Zhang, Yongkui; Song, Hang [Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu ,610065 (China); Cai, Lulu; Ma, Liang; Wang, Guangcheng [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Chen, Lijuan, E-mail: lijuan17@hotmail.com [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Wang, Wenwen [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China)

2012-12-01

Biogenic calcium carbonate has come to the attention of many researchers as a promising drug delivery system due to its safety, pH sensitivity and the large volume of information already in existence on its medical use. In this study, we employed bovine serum albumin (BSA) as an additive to synthesize a series of porous calcium carbonate microspheres (CCMS). These spheres, identified as vaterite, are stable both in aqueous solutions and organic solvents. Camptothecin, an effective anticancer agent, was loaded into the CCMS by simple diffusion and adsorption. The camptothecin loaded CCMS showed sustained cell growth inhibitory activity and a pH dependent release of camptothecin. With a few hours, the release is negligible under physiological conditions (pH = 7.4) but almost complete at pH 4 to 6 (i.e. pHs found in lysosomes and solid tumor tissue respectively). These findings suggest that porous, biogenic calcium carbonate microspheres could be promising carriers for the safe and efficient delivery of anticancer drugs of low aqueous solubility. - Highlights: Black-Right-Pointing-Pointer BSA-doped calcium carbonate microspheres with porous structure were prepared. Black-Right-Pointing-Pointer Camptothecin was encapsulated in the spherical microparticles with encapsulation efficiency up to 11%. Black-Right-Pointing-Pointer The release of encapsulated camptothecin is pH dependent Black-Right-Pointing-Pointer In vitro studies showed an effective anticancer activity of the camptothecin- microspheres.

Functionalized silica nanoparticles as a carrier for Betamethasone Sodium Phosphate: Drug release study and statistical optimization of drug loading by response surface method.

Science.gov (United States)

Ghasemnejad, M; Ahmadi, E; Mohamadnia, Z; Doustgani, A; Hashemikia, S

2015-11-01

Mesoporous silica nanoparticles with a hexagonal structure (SBA-15) were synthesized and modified with (3-aminopropyl) triethoxysilane (APTES), and their performance as a carrier for drug delivery system was studied. Chemical structure and morphology of the synthesized and modified SBA-15 were characterized by SEM, BET, TEM, FT-IR and CHN technique. Betamethasone Sodium Phosphate (BSP) as a water soluble drug was loaded on the mesoporous silica particle for the first time. The response surface method was employed to obtain the optimum conditions for the drug/silica nanoparticle preparation, by using Design-Expert software. The effect of time, pH of preparative media, and drug/silica ratio on the drug loading efficiency was investigated by the software. The maximum loading (33.69%) was achieved under optimized condition (pH: 1.8, time: 3.54 (h) and drug/silica ratio: 1.7). The in vitro release behavior of drug loaded particles under various pH values was evaluated. Finally, the release kinetic of the drug was investigated using the Higuchi and Korsmeyer-Peppas models. Cell culture and cytotoxicity assays revealed the synthesized product doesn't have any cytotoxicity against human bladder cell line 5637. Accordingly, the produced drug-loaded nanostructures can be applied via different routes, such as implantation and topical or oral administration. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Theoretical study on the cage-like nanostructures formed by amino acids and their potential applications as drug carriers

Science.gov (United States)

Weng, Pei Pei; Fan, Jian Fen; Lin, Hui Fang; Zhao, Xin; Si, Xia Lan

2017-12-01

The cage-like octamer, decamer and dodecamer constructed from aspartic acid monomers have been studied to explore their potential applications as drug carriers using the density functional theory. The calculation results indicate that these stable cage-like oligomers are mainly connected by the -C=O…HOOC- and -HN…HOOC- H-bonds and still keep stability and good drum-shaped topologies after the incorporation of 5-fluorouracil, paraldehyde and C24, respectively. The self-assembled cage-like oligomers may be applied to the preparation of new biological materials and the design of drug delivery systems.

Role of different biodegradable polymers on the permeability of ciprofloxacin

OpenAIRE

Chakraborti, Chandra Kanti; Sahoo, Subhashree; Behera, Pradipta Kumar

2014-01-01

Since permeability across biological membranes is a key factor in the absorption and distribution of drugs, drug permeation characteristics of three oral suspensions of ciprofloxacin were designed and compared. The three suspensions of ciprofloxacin were prepared by taking biodegradable polymers such as carbopol 934, carbopol 940, and hydroxypropyl methylcellulose (HPMC). The permeability study was performed by using a Franz diffusion cell through both synthetic cellulose acetate membrane and...

Clinical evaluation of domestic biodegradable drug-eluting stents in the treatment of coronary heart disease

International Nuclear Information System (INIS)

Yu Hongying; Suo Chuantao; Shang Ruiping

2009-01-01

Objective: To evaluate the safety and efficacy of domestic biodegradable drug-eluting stent, EXCEL, in clinical treatment of coronary heart disease. Methods: During the period of Jan. 2008-Oct. 2008, 100 patients with coronary heart disease who consented to PCI and postoperative coronary angiography were selected and enrolled in the study. The patients were divided into EXCEL group (n = 58) and Cypher group (n = 42). The immediate successful rate of interventional therapy and the complications occurred during hospitalization were observed. Postoperative follow-up and checkup coronary angiography were conducted. Results: No significant difference in the relevant clinical data, in the number and type of diseased coronary branch and in the mean length of implanted stents existed between two groups. Also, no statistically significant difference in the occurrence of major adverse cardiac event (MACE), in-stent restenosis and thrombosis was present between two groups. Conclusion: Compared with Cypher stenting, EXCEL stenting carries similar, i.e. rather low, occurrence of MACE and in-stent restenosis. (authors)

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.

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

Directory of Open Access Journals (Sweden)

Chai HJ

2017-01-01

Full Text Available Hann-Juang Chai,1 Lik-Voon Kiew,1 Yunni Chin,1 Anwar Norazit,2 Suzita Mohd Noor,2 Yoke-Lin Lo,3,4 Chung-Yeng Looi,1 Yeh-Siang Lau,1 Tuck-Meng Lim,5 Won-Fen Wong,6 Nor Azizan Abdullah,1 Munavvar Zubaid Abdul Sattar,7 Edward J Johns,8 Zamri Chik,1 Lip-Yong Chung3 1Department of Pharmacology, 2Department of Biomedical Science, 3Department of Pharmacy, Faculty of Medicine, University of Malaya, 4School of Pharmacy, International Medical University, Kuala Lumpur, 5Department of Chemical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, 6Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, 7School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Malaysia; 8Department of Physiology, University College Cork, Cork, Republic of Ireland Background and purpose: 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.Experimental approach: 3H-deoxycytidine-labeled PGs (17 or 41 kDa and 3H-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-aminoethylbenzenesulfonyl 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.Results: 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 �

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

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.

Norfloxacin release from surfactant-free nanoparticles of poly (DL-lactide-co-glycolide) and biodegradation

Energy Technology Data Exchange (ETDEWEB)

Kweon, J.K. [Chosun College of Science and Technology, Gwangju (Korea); Jeong, Y.I. [Chonnam National University, Gwangju (Korea); Jang, M.K. [Suncheon National University, Suncheon (Korea); Lee, C.H. [Korea Food and Drug Administration, Seoul (Korea); Nah, J.W. [Suncheon National University, Suncheon (Korea)

2002-07-01

We have prepared the surfactant-free nanoparticles of poly(DL- lactide-co-glycolide)(PLGA) by dialysis method and their physicochemical properties such as particle size and drug contents were investigated against various solvent. The size of PLGA nanoparticles prepared by using dimethylacetamide (DMAc), dimethylformamide (DMF), and dimethylsulfoxide (DMSO) was smaller than that from acetone. Also, the order of drug contents was DMAc>DMF>DMSO=acetone. These phenomena could be expected from the fact that solvent affects the size of nanoparticles and drug contents. The PLGA nanoparticles have a good spherical shapes as observed from scanning electron microscopy (SEM) and transmission electron microscopy (TEM), Also, surfactant-free nanoparticles entrapping norfloxacin (NFx) have a good drug loading capacity without free-drug on the surface of nanoparticles confirmed by the analysis of X-ray powder diffraction. Release kinetics of NFx used as a model drug was governed not only by drug contents but also by particle size. Also, the biodegradation rate of PLGA nanoparticles prepared from DMF was faster than that prepared from acetone, indicating that the biodegradation of PLGA nanoparticles is size-dependent. (author). 25 refs., 3 tabs., 5 figs.

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

Dissolution enhancement of a model poorly water-soluble drug, atorvastatin, with ordered mesoporous silica: comparison of MSF with SBA-15 as drug carriers.

Science.gov (United States)

Maleki, Aziz; Hamidi, Mehrdad

2016-01-01

The purpose of this study was to develop mesoporous silica materials incorporated with poorly water-soluble drug atorvastatin calcium (AC) in order to improve drug dissolution, and intended to be orally administrated. A comparison between 2D-hexagonal silica nanostructured SBA-15 and mesocellular siliceous foam (MSF) with continuous 3D pore system on drug release rate was investigated. AC-loaded mesoporous silicas were characterized thorough N2 adsorption-desorption analysis, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and dynamic light scattering (DLS). Results demonstrated a successful incorporation of AC into the silica-based hosts. The results taken from the drug release tests were also analyzed using different parameters, namely similarity factor (f2), difference factor (f1), dissolution efficiency (DE%), mean dissolution rate (MDR) and dissolution time (tm%). It confirmed a significant enhancement in the release profile of atorvastatin calcium with SBA-15, and MSF as drug carrier. Moreover, in comparison with SBA-15, MSF showed faster release rate of AC in enzyme-free simulated gastric fluid (pH 1.2). We believed that our findings can help the use of mesoporous silica materials in improving bioavailability of poorly water-soluble drugs.

Dual tumor-targeted poly(lactic-co-glycolic acid–polyethylene glycol–folic acid nanoparticles: a novel biodegradable nanocarrier for secure and efficient antitumor drug delivery

Directory of Open Access Journals (Sweden)

Chen J

2017-08-01

Full Text Available Jia Chen,1,2,* Qi Wu,1,* Li Luo,1 Yi Wang,1 Yuan Zhong,1 Han-Bin Dai,1 Da Sun,1,3 Mao-Ling Luo,4 Wei Wu,1 Gui-Xue Wang1 1Key Laboratory for Biorheological Science and Technology, Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College, Chongqing University, Chongqing, 2Institute of Laboratory Animals, Sichuan Academy of Medical Science, Sichuan Provincial People’s Hospital, Chengdu, 3Institute of Life Sciences, Wenzhou University, Wenzhou, 4School of Medicine, Wuhan University, Wuhan, China *These authors contributed equally to this work Abstract: Further specific target-ability development of biodegradable nanocarriers is extremely important to promote their security and efficiency in antitumor drug-delivery applications. In this study, a facilely prepared poly(lactic-co-glycolic acid (PLGA–polyethylene glycol (PEG–folic acid (FA copolymer was able to self-assemble into nanoparticles with favorable hydrodynamic diameters of around 100 nm and negative surface charge in aqueous solution, which was expected to enhance intracellular antitumor drug delivery by advanced dual tumor-target effects, ie, enhanced permeability and retention induced the passive target, and FA mediated the positive target. Fluorescence-activated cell-sorting and confocal laser-scanning microscopy results confirmed that doxorubicin (model drug loaded into PLGA-PEG-FA nanoparticles was able to be delivered efficiently into tumor cells and accumulated at nuclei. In addition, all hemolysis, 3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium, and zebrafish-development experiments demonstrated that PLGA-PEG-FA nanoparticles were biocompatible and secure for biomedical applications, even at high polymer concentration (0.1 mg/mL, both in vitro and in vivo. Therefore, PLGA-PEG-FA nanoparticles provide a feasible controlled-release platform for secure and efficient antitumor drug

Beyond liposomes: Recent advances on lipid based nanostructures for poorly soluble/poorly permeable drug delivery.

Science.gov (United States)

Teixeira, M C; Carbone, C; Souto, E B

2017-10-01

Solid lipid nanoparticle (SLN), nanostructured lipid carriers (NLC) and hybrid nanoparticles, have gained increasing interest as drug delivery systems because of their potential to load and release drugs from the Biopharmaceutical classification system (BCS) of class II (low solubility and high permeability) and of class IV (low solubility and low permeability). Lipid properties (e.g. high solubilizing potential, biocompatibility, biotolerability, biodegradability and distinct route of absorption) contribute for the improvement of the bioavailability of these drugs for a set of administration routes. Their interest continues to grow, as translated by the number of patents being field worldwide. This paper discusses the recent advances on the use of SLN, NLC and lipid-polymer hybrid nanoparticles for the loading of lipophilic, poorly water-soluble and poorly permeable drugs, being developed for oral, topical, parenteral and ocular administration, also discussing the industrial applications of these systems. A review of the patents filled between 2014 and 2017, concerning the original inventions of lipid nanocarriers, is also provided. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ceramic/polymer nanocomposites with tunable drug delivery capability at specific disease sites.

Science.gov (United States)

Liu, Huinan; Webster, Thomas J

2010-06-01

Pharmaceutical agents are often used to stimulate new bone formation for the treatment of bone injuries or diseases (such as osteoporosis). However, there are several problems associated with current orthopedic drug delivery methods. First, conventional systemic administration of pharmaceutical agents may not effectively reach targeted sites and, thus, they can cause nonspecific bone formation in areas not affected by injury or disease. Second, even if intentionally delivered or implanted locally to the damaged bone tissue, these agents tend to rapidly diffuse into adjacent tissues due to weak physical bonding to their drug carriers, which limits their potential to promote prolonged bone formation in targeted areas of bone disease. Therefore, in this study, biodegradable ceramic/polymer nanocomposites were explored as novel drug carriers for orthopedic applications to prolong local drug release and, thus, improve drug effectiveness at bone disease sites. Specifically, a bone morphogenetic protein (BMP-7) derived peptide (DIF-7c) was used as a model drug in this study and was first loaded onto nanocrystalline hydroxyapatite (nano-HA) by either covalent chemical attachment or physical adsorption. These drug-carrying nano-HA particles were then dispersed into a degradable polymer (poly-lactide-co-glycolide or PLGA) matrix to create an implantable system capable of long-term drug release. The aminophase silane covalent chemical immobilization process was utilized in this study. These nanocomposite-based drug delivery systems were then characterized for drug loading efficiency and in vitro drug release. Results demonstrated that DIF-7c was successfully immobilized onto nano-HA placed in PLGA. Moreover, a greater prolonged two-phase release profile (of more than 3 months) was achieved when using aminophase silane chemical immobilization to nano-HA particles. Since previous studies have demonstrated greater in vivo bone growth on nano- compared with micron-HA particles

Hydrophobic Drug-Loaded PEGylated Magnetic Liposomes for Drug-Controlled Release

Science.gov (United States)

Hardiansyah, Andri; Yang, Ming-Chien; Liu, Ting-Yu; Kuo, Chih-Yu; Huang, Li-Ying; Chan, Tzu-Yi

2017-05-01

Less targeted and limited solubility of hydrophobic-based drug are one of the serious obstacles in drug delivery system. Thus, new strategies to enhance the solubility of hydrophobic drug and controlled release behaviors would be developed. Herein, curcumin, a model of hydrophobic drug, has been loaded into PEGylated magnetic liposomes as a drug carrier platform for drug controlled release system. Inductive magnetic heating (hyperthermia)-stimulated drug release, in vitro cellular cytotoxicity assay of curcumin-loaded PEGylated magnetic liposomes and cellular internalization-induced by magnetic guidance would be investigated. The resultant of drug carriers could disperse homogeneously in aqueous solution, showing a superparamagnetic characteristic and could inductive magnetic heating with external high-frequency magnetic field (HFMF). In vitro curcumin release studies confirmed that the drug carriers exhibited no significant release at 37 °C, whereas exhibited rapid releasing at 45 °C. However, it would display enormous (three times higher) curcumin releasing under the HFMF exposure, compared with that without HFMF exposure at 45 °C. In vitro cytotoxicity test shows that curcumin-loaded PEGylated magnetic liposomes could efficiently kill MCF-7 cells in parallel with increasing curcumin concentration. Fluorescence microscopy observed that these drug carriers could internalize efficiently into the cellular compartment of MCF-7 cells. Thus, it would be anticipated that the novel hydrophobic drug-loaded PEGylated magnetic liposomes in combination with inductive magnetic heating are promising to apply in the combination of chemotherapy and thermotherapy for cancer therapy.

Benzothiophen-pyrazine scaffold as a potential membrane targeting drug carrier

International Nuclear Information System (INIS)

Mazuryk, Olga; Niemiec, Elżbieta; Stochel, Grażyna; Gillaizeau, Isabelle; Brindell, Małgorzata

2013-01-01

The fluorescent properties of 2,5-di(benzo[b]thiophen-2-yl)pyrazine as a potential membrane targeting drug carrier were characterized and it was shown that its fluorescence intensity was much higher in organic solvent than in water. The embedding of studied compound by liposomes leads to ca. 2 orders of magnitude increase in its fluorescence intensity, suggesting its preferential accumulation in membranes. Preliminary biological studies showed its ability to accumulate in cells, and the concentration of 10 μM was sufficient for homogeneous staining of cells. The treatment of mouse carcinoma CT26 cells with studied compound up to 200 μM resulted in decreasing of viable cells by ca. 30%. Its reactivity towards albumin was found to be moderate with an association constant of 6×10 4 M −1 , while no interaction with DNA was observed. Our findings encourage for further studies on functionalization of this molecule to obtain a new class of anticancer drugs targeting membrane. Highlights: ► The fluorescence of 2,5-di(benzo[b]thiophen-2-yl)pyrazine is solvent dependent. ► Weak fluorescence is found in water while high in organic solvents (DMSO, chloroform). ► Embedding of compound in liposomes remarkably increased its fluorescence. ► No interaction with DNA is observed but moderate reactivity towards albumin is found. ► Homogeneous staining of cells is feasible using nontoxic dose of compound

On the intracellular release mechanism of hydrophobic cargo and its relation to the biodegradation behavior of mesoporous silica nanocarriers.

Science.gov (United States)

von Haartman, Eva; Lindberg, Desiré; Prabhakar, Neeraj; Rosenholm, Jessica M

2016-12-01

The intracellular release mechanism of hydrophobic molecules from surface-functionalized mesoporous silica nanoparticles was studied in relation to the biodegradation behavior of the nanocarrier, with the purpose of determining the dominant release mechanism for the studied drug delivery system. To be able to follow the real-time intracellular release, a hydrophobic fluorescent dye was used as model drug molecule. The in vitro release of the dye was investigated under varying conditions in terms of pH, polarity, protein and lipid content, presence of hydrophobic structures and ultimately, in live cancer cells. Results of investigating the drug delivery system show that the degradation and drug release mechanisms display a clear interdependency in simple aqueous solvents. In pure aqueous media, the cargo release was primarily dependent on the degradation of the nanocarrier, while in complex media, mimicking intracellular conditions, the physicochemical properties of the cargo molecule itself and its interaction with the carrier and/or surrounding media were found to be the main release-governing factors. Since the material degradation was retarded upon loading with hydrophobic guest molecules, the cargo could be efficiently delivered into live cancer cells and released intracellularly without pronounced premature release under extracellular conditions. From a rational design point of view, pinpointing the interdependency between these two processes can be of paramount importance considering future applications and fundamental understanding of the drug delivery system. Copyright © 2016 Elsevier B.V. All rights reserved.

Biomimetics in drug delivery systems: A critical review.

Science.gov (United States)

Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh

2017-05-10

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

Biodegradability of plastics.

Science.gov (United States)

Tokiwa, Yutaka; Calabia, Buenaventurada P; Ugwu, Charles U; Aiba, Seiichi

2009-08-26

Plastic is a broad name given to different polymers with high molecular weight, which can be degraded by various processes. However, considering their abundance in the environment and their specificity in attacking plastics, biodegradation of plastics by microorganisms and enzymes seems to be the most effective process. When plastics are used as substrates for microorganisms, evaluation of their biodegradability should not only be based on their chemical structure, but also on their physical properties (melting point, glass transition temperature, crystallinity, storage modulus etc.). In this review, microbial and enzymatic biodegradation of plastics and some factors that affect their biodegradability are discussed.

Synthesis of piroxicam loaded novel electrospun biodegradable nanocomposite scaffolds for periodontal regeneration

Energy Technology Data Exchange (ETDEWEB)

Farooq, Ariba [Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Yar, Muhammad, E-mail: drmyar@ciitlahore.edu.pk [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Khan, Abdul Samad; Shahzadi, Lubna; Siddiqi, Saadat Anwar [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Mahmood, Nasir [Department of Allied Health Sciences and Chemical Pathology, University of Health Sciences, Lahore (Pakistan); Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore (Pakistan); Rauf, Abdul [Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Qureshi, Zafar-ul-Ahsan [Veterinary Research Institute, Lahore (Pakistan); Manzoor, Faisal; Chaudhry, Aqif Anwar [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Rehman, Ihtesham ur [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Department of Materials Science and Engineering, The Kroto Research Institute, The University of Sheffield, North Campus, Broad Lane, Sheffield S3 7HQ (United Kingdom)

2015-11-01

Development of biodegradable composites having the ability to suppress or eliminate the pathogenic micro-biota or modulate the inflammatory response has attracted great interest in order to limit/repair periodontal tissue destruction. The present report includes the development of non-steroidal anti-inflammatory drug encapsulated novel biodegradable chitosan (CS)/poly(vinyl alcohol) (PVA)/hydroxyapatite (HA) electro-spun (e-spun) composite nanofibrous mats and films and study of the effect of heat treatment on fibers and films morphology. It also describes comparative in-vitro drug release profiles from heat treated and control (non-heat treated) nanofibrous mats and films containing varying concentrations of piroxicam (PX). Electrospinning was used to obtain drug loaded ultrafine fibrous mats. The physical/chemical interactions were evaluated by Fourier Transform Infrared (FT-IR) spectroscopy. The morphology, structure and pore size of the materials were investigated by scanning electron microscopy (SEM). The thermal behavior of the materials was investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Control (not heat treated) and heat treated e-spun fibers mats and films were tested for in vitro drug release studies at physiological pH 7.4 and initially, as per requirement burst release patterns were observed from both fibers and films and later sustained release profiles were noted. In vitro cytocompatibility was performed using VERO cell line of epithelial cells and all the synthesized materials were found to be non-cytotoxic. The current observations suggested that these materials are potential candidates for periodontal regeneration. - Highlights: • Novel non-steroidal anti-inflammatory drug encapsulated biodegradable electrospun nanocomposite scaffolds were synthesized. • Heat treatment displayed great influence on the morphology of scaffolds. • Fiber diameter was decreased and pore size was increased after heat

Synthesis of piroxicam loaded novel electrospun biodegradable nanocomposite scaffolds for periodontal regeneration

International Nuclear Information System (INIS)

Farooq, Ariba; Yar, Muhammad; Khan, Abdul Samad; Shahzadi, Lubna; Siddiqi, Saadat Anwar; Mahmood, Nasir; Rauf, Abdul; Qureshi, Zafar-ul-Ahsan; Manzoor, Faisal; Chaudhry, Aqif Anwar; Rehman, Ihtesham ur

2015-01-01

Development of biodegradable composites having the ability to suppress or eliminate the pathogenic micro-biota or modulate the inflammatory response has attracted great interest in order to limit/repair periodontal tissue destruction. The present report includes the development of non-steroidal anti-inflammatory drug encapsulated novel biodegradable chitosan (CS)/poly(vinyl alcohol) (PVA)/hydroxyapatite (HA) electro-spun (e-spun) composite nanofibrous mats and films and study of the effect of heat treatment on fibers and films morphology. It also describes comparative in-vitro drug release profiles from heat treated and control (non-heat treated) nanofibrous mats and films containing varying concentrations of piroxicam (PX). Electrospinning was used to obtain drug loaded ultrafine fibrous mats. The physical/chemical interactions were evaluated by Fourier Transform Infrared (FT-IR) spectroscopy. The morphology, structure and pore size of the materials were investigated by scanning electron microscopy (SEM). The thermal behavior of the materials was investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Control (not heat treated) and heat treated e-spun fibers mats and films were tested for in vitro drug release studies at physiological pH 7.4 and initially, as per requirement burst release patterns were observed from both fibers and films and later sustained release profiles were noted. In vitro cytocompatibility was performed using VERO cell line of epithelial cells and all the synthesized materials were found to be non-cytotoxic. The current observations suggested that these materials are potential candidates for periodontal regeneration. - Highlights: • Novel non-steroidal anti-inflammatory drug encapsulated biodegradable electrospun nanocomposite scaffolds were synthesized. • Heat treatment displayed great influence on the morphology of scaffolds. • Fiber diameter was decreased and pore size was increased after heat

Elastin-Like Recombinamers As Smart Drug Delivery Systems.

Science.gov (United States)

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

2018-02-19

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

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

Science.gov (United States)

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

2005-10-20

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

Biodegradability of Plastics

Directory of Open Access Journals (Sweden)

Yutaka Tokiwa

2009-08-01

Full Text Available Plastic is a broad name given to different polymers with high molecular weight, which can be degraded by various processes. However, considering their abundance in the environment and their specificity in attacking plastics, biodegradation of plastics by microorganisms and enzymes seems to be the most effective process. When plastics are used as substrates for microorganisms, evaluation of their biodegradability should not only be based on their chemical structure, but also on their physical properties (melting point, glass transition temperature, crystallinity, storage modulus etc.. In this review, microbial and enzymatic biodegradation of plastics and some factors that affect their biodegradability are discussed.

Biodegradation of Carbon Nanotubes, Graphene, and Their Derivatives.

Science.gov (United States)

Chen, Ming; Qin, Xiaosheng; Zeng, Guangming

2017-09-01

Carbon nanotubes (CNTs), graphene (GRA), and their derivatives are promising materials for a wide range of applications such as pollutant removal, enzyme immobilization, bioimaging, biosensors, and drug delivery and are rapidly increasing in use and increasingly mass produced. The biodegradation of carbon nanomaterials by microbes and enzymes is now of great importance for both reducing their toxicity to living organisms and removing them from the environment. Here we review recent progress in the biodegradation field from the point of view of the primary microbes and enzymes that can degrade these nanomaterials, along with experimental and molecular simulation methods for the exploration of nanomaterial degradation. Further efforts should primarily aim toward expanding the repertoire of microbes and enzymes and exploring optimal conditions for the degradation of nanomaterials. Copyright © 2016 Elsevier Ltd. All rights reserved.

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...

Molecular Dynamics Studies of Liposomes as Carriers for Photosensitizing Drugs: Development, Validation, and Simulations with a Coarse-Grained Model.

Science.gov (United States)

Jämbeck, Joakim P M; Eriksson, Emma S E; Laaksonen, Aatto; Lyubartsev, Alexander P; Eriksson, Leif A

2014-01-14

Liposomes are proposed as drug delivery systems and can in principle be designed so as to cohere with specific tissue types or local environments. However, little detail is known about the exact mechanisms for drug delivery and the distributions of drug molecules inside the lipid carrier. In the current work, a coarse-grained (CG) liposome model is developed, consisting of over 2500 lipids, with varying degrees of drug loading. For the drug molecule, we chose hypericin, a natural compound proposed for use in photodynamic therapy, for which a CG model was derived and benchmarked against corresponding atomistic membrane bilayer model simulations. Liposomes with 21-84 hypericin molecules were generated and subjected to 10 microsecond simulations. Distribution of the hypericins, their orientations within the lipid bilayer, and the potential of mean force for transferring a hypericin molecule from the interior aqueous "droplet" through the liposome bilayer are reported herein.

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...

Nanoemulsions as self-emulsified drug delivery carriers for enhanced permeability of the poorly water-soluble selective β₁-adrenoreceptor blocker Talinolol.

Science.gov (United States)

Ghai, Damanjeet; Sinha, Vivek Ranjan

2012-07-01

To enhance the bioavailability of the poorly water-soluble drug talinolol, a self-nanoemulsifying drug delivery system (SNEDDS) comprising 5% (w/v) Brij-721 ethanolic solution (Smix), triacetin, and water, in the ratio of 40:20:40 (% w/w) was developed by constructing pseudo-ternary phase diagrams and evaluated for droplet size, polydispersity index, and surface morphology of nanoemulsions. The effect of nanodrug carriers on drug release and permeability was assessed using stripped porcine jejunum and everted rat gut sac method and compared with hydroalcoholic drug solution, oily solution, and conventional emulsion and suspension. The SNEDDS showed a significant (P water-soluble beta-blocker talinolol. Significant increase in drug release, permeability, and in vivo bioavailability were demonstrated as compared to standard drug suspension. Copyright © 2012 Elsevier Inc. All rights reserved.

Biodegradable Magnetic Silica@Iron Oxide Nanovectors with Ultra-Large Mesopores for High Protein Loading, Magnetothermal Release, and Delivery

KAUST Repository

Omar, Haneen

2016-11-29

The delivery of large cargos of diameter above 15 nm for biomedical applications has proved challenging since it requires biocompatible, stably-loaded, and biodegradable nanomaterials. In this study, we describe the design of biodegradable silica-iron oxide hybrid nanovectors with large mesopores for large protein delivery in cancer cells. The mesopores of the nanomaterials spanned from 20 to 60 nm in diameter and post-functionalization allowed the electrostatic immobilization of large proteins (e.g. mTFP-Ferritin, ~ 534 kDa). Half of the content of the nanovectors was based with iron oxide nanophases which allowed the rapid biodegradation of the carrier in fetal bovine serum and a magnetic responsiveness. The nanovectors released large protein cargos in aqueous solution under acidic pH or magnetic stimuli. The delivery of large proteins was then autonomously achieved in cancer cells via the silica-iron oxide nanovectors, which is thus a promising for biomedical applications.

Effects of Spray-Drying and Choice of Solid Carriers on Concentrations of Labrasol® and Transcutol® in Solid Self-Microemulsifying Drug Delivery Systems (SMEDDS

Directory of Open Access Journals (Sweden)

Christopher Wai-Kei Lam

2013-01-01

Full Text Available Solid self-microemulsifying drug delivery systems (SMEDDS have been used increasingly for improving the bioavailability of hydrophobic drugs. Labrasol® and Transcutol® are used widely as surfactant and solubilizer in the formulation of solid SMEDDS. We investigated the effects of spray-drying and the use of different solid carriers on concentrations of Labrasol® and Transcutol® in solid SMEDDS with scutellarin as the formulated drug. Liquid and gas chromatography tandem mass spectrometry (LC-MS and GC-MS methods were developed for measuring low concentrations of Labrasol® and Transcutol®. In the preparation of solid SMEDDS, lactose, hydroxypropylmethyl cellulose (HPMC and microcrystalline cellulose (MCC were used as solid carriers. Judging from the retention ratios of Labrasol® and Transcutol®, the droplet size of solid SMEDDS increased after spray-drying of liquid SMEDDS, and concentrations of these excipients decreased after the solidifying procedure. In such reduction, Lactose and HPMC were found to preserve Labrasol® and Transcutol® better than MCC during spray-drying, and the resultant droplet sizes were smaller than that of MCC. Labrasol® and Transcutol® showed good thermal stability at 60 °C degree for 10 days. It can be concluded that spray-drying could increase the droplet size of solid SMEDDS and decreased the concentration of Labrasol® and Transcutol® therein, while water-soluble solid carriers could preserve Labrasol® and Transcutol® better than insoluble carriers in the solid SMEDDS.

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

Science.gov (United States)

Abd El-Rehim, H. A.; Hegazy, E. A.; Khalil, F. H.; Hamed, N. A.

2007-01-01

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 p Ka of PAAc. The prepared inter-polymer complex could be used for application as drug carriers.

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.

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

Multifunctional Amine Mesoporous Silica Spheres Modified with Multiple Amine as Carriers for Drug Release

Directory of Open Access Journals (Sweden)

Yan Li

2018-01-01

Full Text Available Mesoporous silica spheres were synthesized by using Stöber theory (MSN-40. Calcination of the mesostructured phase resulted in the starting solid. Organic modification with aminopropyl groups resulted in two MSN-40 materials: named MSN-NH2 and MSN-DQ-40, respectively. These two kinds of samples with different pore sizes (obtained from 3-[2-(2-aminoethylaminoethylamino]propyl-trimethox-ysilane (NQ-62 and modified NQ-62 showed control of the delivery rate of ibuprofen (IBU from the siliceous matrix. The obtained sample from modified NQ-62 has an increased loading rate and shows better control of the delivery rate of IBU than the obtained sample from NQ-62. These three solids were characterized using standard solid state procedures. During tests of in vitro drug release, an interesting phenomenon was observed: at high pH (pH 7.45, IBU in all carriers was released slowly; at low pH (pH 4.5, only a part of the IBU was slowly released from this carrier within 25 hours; most IBU was effectively confined in mesoporous material, but the remaining IBU was released rapidly and completely after 25 hours.

Physical stability, biocompatibility and potential use of hybrid iron oxide-gold nanoparticles as drug carriers

Energy Technology Data Exchange (ETDEWEB)

Barnett, Christopher M. [School of Pharmacy, Keele University (United Kingdom); Gueorguieva, Mariana [Institute of Medical Science and Technology, University of Dundee (United Kingdom); Lees, Martin R. [University of Warwick, Physics Department (United Kingdom); McGarvey, David J. [School of Physical and Geographical Sciences, Keele University, Lennard-Jones Laboratories (United Kingdom); Hoskins, Clare, E-mail: c.hoskins@keele.ac.uk [Institute for Science and Technology in Medicine, Keele University (United Kingdom)

2013-06-15

Hybrid nanoparticles (HNPs) such as iron oxide-gold nanoparticles are currently being exploited for their potential application in image-guided therapies. However, little investigation has been carried out into their physical or chemical stability and potential cytotoxicity in biological systems. Here, we determine the HNPs physical stability over 6 months and chemical stability in physiological conditions, and estimate the biological activity of uncoated and poly(ethylene glycol) coated nanoparticles on human pancreatic adenocarcinoma (BxPC-3) and differentiated human monocyte cells (U937). The potential of these HNPs to act as drug carrier vehicles was determined using the model drug 6-Thioguanine (6-TG). The data showed that the HNPs maintained their structural integrity both physically and chemically throughout the duration of the studies. In addition, negligible cytotoxicity or free radical production was observed in the cell lines tested. The 6-TG was successfully conjugated; with a ratio of 3:1:10 Fe:Au:6-TG (wt:wt:wt). After incubation with BxPC-3 cells, enhanced cellular uptake was reported with the 6-TG-conjugated HNPs compared with free drug along with a 10-fold decrease in IC{sub 50}. This exciting data highlights the potential of HNPs for use in image-guided drug delivery.

Formulation and evaluation of biodegradable nanoparticles for the oral delivery of fenretinide.

Science.gov (United States)

Graves, Richard A; Ledet, Grace A; Glotser, Elena Y; Mitchner, Demaurian M; Bostanian, Levon A; Mandal, Tarun K

2015-08-30

Fenretinide is an anticancer drug with low water solubility and poor bioavailability. The goal of this study was to develop biodegradable polymeric nanoparticles of fenretinide with the intent of increasing its apparent aqueous solubility and intestinal permeability. Three biodegradable polymers were investigated for this purpose: two different poly lactide-co-glycolide (PLGA) polymers, one acid terminated and one ester terminated, and one poly lactide-co-glycolide/polyethylene glycol (PLGA/PEG) diblock copolymer. Nanoparticles were obtained by using an emulsification solvent evaporation technique. The formulations were characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and particle size analysis. Dissolution studies and Caco-2 cell permeation studies were also carried out for all formulations. Ultra high performance liquid chromatography coupled with mass spectrometry (UPLC/MS) and ultraviolet detection was used for the quantitative determination of fenretinide. Drug loading and the type of polymer affected the nanoparticles' physical properties, drug release rate, and cell permeability. While the acid terminated PLGA nanoparticles performed the best in drug release, the ester terminated PLGA nanoparticles performed the best in the Caco-2 cell permeability assays. The PLGA/PEG copolymer nanoparticles performed better than the formulations with ester terminated PLGA in terms of drug release but had the poorest performance in terms of cell permeation. All three categories of formulations performed better than the drug alone in both drug release and cell permeation studies. Copyright © 2015 Elsevier B.V. All rights reserved.

The use of biodegradable microneedle patches to increase penetration of topical steroid for prurigo nodularis.

Science.gov (United States)

Shin, Jung U; Kim, Jung Dong; Kim, Hong Kee; Kang, Hong Kyu; Joo, Chulmin; Lee, Ju Hee; Jeong, Do Hyeon; Song, Seungri; Chu, Howard; Lee, Jung Soo; Lee, Hemin; Lee, Kwang Hoon

2018-02-01

The stratum corneum is an almost impermeable barrier. Recently, microneedles have been used to increase drug delivery passing the stratum corneum by incorporating the drug within the microneedle or by coating the surface of the microneedle with the drug. This study was performed to investigate whether applying a biodegradable microneedle patch after topical steroid application increases penetration of the steroid in vitro, as well as treatment efficacy in patients with prurigo nodularis. In vitro penetration of topical steroids after biodegradable microneedle patch application was measured using a 3D skin model. To evaluate the treatment efficacy of the combination of biodegradable microneedle and topical steroids, a split-body clinical study was performed. Penetration of topical steroid in the in vitro skin model was significantly greater in the microneedle-applied skin. In a split-body clinical study with prurigo nodularis patients, the area and height of skin lesions decreased after four weeks of treatment on both sides, however, the microneedle patch side exhibited a significantly greater decrease in both area and height, compared to the control side. The pruritus visual analogue scale was also significantly lower on the microneedle side. We suggest that simply applying a microneedle patch after topical steroid application could be a useful strategy for treating refractory skin diseases such as prurigo nodularis.

Sugarcane bagasse lignin, and silica gel and magneto-silica as drug vehicles for development of innocuous methotrexate drug against rheumatoid arthritis disease in albino rats.

Science.gov (United States)

Wahba, Sanaa M R; Darwish, Atef S; Shehata, Iman H; Abd Elhalem, Sahar S

2015-03-01

The present study clarifies co-therapy action of deliveries from their textural changes point of view. Methotrexate (MTX) was immobilized onto biodegradable lignin, silica gel and iron/silica nanocomposite. Loaded-MTX was i.p. injected into albino rats at doses of 0.25 and 0.5mg/kg/week for 2.5months, after which spleen, liver, testes and knee joint tissues were collected for tests. IFN-γ and IL-17A mRNA gene expressions in spleen in all biological samples were determined by RT-PCR. Physicochemical features of drug carriers were monitored by XRD, BET-PSD, SEM and TEM. Drug inflammatory-site targeting was found to be closely related to the physico-features of deliverers. The interlayered lignin of micro- and meso-pore channels directed MTX toward concealed infected cells in liver and testes tissues, while meso-structured silica flacks satisfied by gathering MTX around knee joints. The magneto-silica nanocomposite targeted MTX toward spleen tissue, which is considered as a lively factory for the production of electron rich compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

Simultaneous biodegradation of carbon tetrachloride and trichloroethylene in a coupled anaerobic/aerobic biobarrier

Energy Technology Data Exchange (ETDEWEB)

Kwon, Kiwook [Department of Civil and Environmental Engineering, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588 (Korea, Republic of); Shim, Hojae [Department of Civil and Environmental Engineering, Faculty of Science and Technology, University of Macau, Macau SAR, 999078 (China); Bae, Wookeun, E-mail: wkbae@hanyang.ac.kr [Department of Civil and Environmental Engineering, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588 (Korea, Republic of); Oh, Juhyun; Bae, Jisu [Department of Civil and Environmental Engineering, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588 (Korea, Republic of)

2016-08-05

Highlights: • Coupled biodegradation of carbon tetrachloride (CT) and trichloroethylene (TCE) in biobarrier with polyethylene glycol carriers. • TCE aerobically cometabolized and CT anaerobically dechlorinated. • Removal efficiencies of over 98%, leaving residuals below or near the regulatory standards. • Coupled aerobic/anaerobic environments established by H{sub 2}O{sub 2} injected at 50% of electron donor. • Longer retention time (from 3.6 to 7.2 days) achieved satisfactory removal at lower temperature (18 °C). - Abstract: Simultaneous biodegradation of carbon tetrachloride (CT) and trichloroethylene (TCE) in a biobarrier with polyethylene glycol (PEG) carriers was studied. Toluene/methanol and hydrogen peroxide (H{sub 2}O{sub 2}) were used as electron donors and an electron acceptor source, respectively, in order to develop a biologically active zone. The average removal efficiencies for TCE and toluene were over 99.3%, leaving the respective residual concentrations of ∼12 and ∼57 μg/L, which are below or close to the groundwater quality standards. The removal efficiency for CT was ∼98.1%, with its residual concentration (65.8 μg/L) slightly over the standards. TCE was aerobically cometabolized with toluene as substrate while CT was anaerobically dechlorinated in the presence of electron donors, with the respective stoichiometric amount of chloride released. The oxygen supply at equivalent to 50% chemical oxygen demand of the injected electron donors supported successful toluene oxidation and also allowed local anaerobic environments for CT reduction. The originally augmented (immobilized in PEG carriers) aerobic microbes were gradually outcompeted in obtaining substrate and oxygen. Instead, newly developed biofilms originated from indigenous microbes in soil adapted to the coupled anaerobic/aerobic environment in the carrier for the simultaneous and almost complete removal of CT, TCE, and toluene. The declined removal rates when temperature

Imaging the intracellular degradation of biodegradable polymer nanoparticles

Directory of Open Access Journals (Sweden)

Anne-Kathrin Barthel

2014-10-01

Full Text Available In recent years, the development of smart drug delivery systems based on biodegradable polymeric nanoparticles has become of great interest. Drug-loaded nanoparticles can be introduced into the cell interior via endocytotic processes followed by the slow release of the drug due to degradation of the nanoparticle. In this work, poly(L-lactic acid (PLLA was chosen as the biodegradable polymer. Although common degradation of PLLA has been studied in various biological environments, intracellular degradation processes have been examined only to a very limited extent. PLLA nanoparticles with an average diameter of approximately 120 nm were decorated with magnetite nanocrystals and introduced into mesenchymal stem cells (MSCs. The release of the magnetite particles from the surface of the PLLA nanoparticles during the intracellular residence was monitored by transmission electron microscopy (TEM over a period of 14 days. It was demonstrated by the release of the magnetite nanocrystals from the PLLA surface that the PLLA nanoparticles do in fact undergo degradation within the cell. Furthermore, even after 14 days of residence, the PLLA nanoparticles were found in the MSCs. Additionally, the ultrastructural TEM examinations yield insight into the long term intercellular fate of these nanoparticles. From the statistical analysis of ultrastructural details (e.g., number of detached magnetite crystals, and the number of nanoparticles in one endosome, we demonstrate the importance of TEM studies for such applications in addition to fluorescence studies (flow cytometry and confocal laser scanning microscopy.

Stimuli-Responsive Liposomes for Controlled Drug Delivery

KAUST Repository

Li, Wengang

2014-01-01

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

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.

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.

Alveolar bone tissue engineering using composite scaffolds for drug delivery

Directory of Open Access Journals (Sweden)

Tomonori Matsuno

2010-08-01

Full Text Available For many years, bone graft substitutes have been used to reconstruct bone defects in orthopedic and dental fields. However, synthetic bone substitutes such as hydroxyapatite or β-tricalcium phosphate have no osteoinductive or osteogenic abilities. Bone tissue engineering has also been promoted as an alternative approach to regenerating bone tissue. To succeed in bone tissue engineering, osteoconductive scaffolding biomaterials should provide a suitable environment for osteogenic cells and provide local controlled release of osteogenic growth factors. In addition, the scaffold for the bone graft substitute should biodegrade to replace the newly formed bone. Recent advances in bone tissue engineering have allowed the creation of composite scaffolds with tailored functional properties. This review focuses on composite scaffolds that consist of synthetic ceramics and natural polymers as drug delivery carriers for alveolar bone tissue engineering.

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

Directory of Open Access Journals (Sweden)

Munawar A. Mohammed

2017-11-01

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

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.

Characterization of gelation process and drug release profile of thermosensitive liquid lecithin/poloxamer 407 based gels as carriers for percutaneous delivery of ibuprofen.

Science.gov (United States)

Djekic, Ljiljana; Krajisnik, Danina; Martinovic, Martina; Djordjevic, Dragana; Primorac, Marija

2015-07-25

Suitability of liquid lecithin (i.e., solution of lecithin in soy bean oil with ∼ 60% w/w of phospholipids) for formation of gels, upon addition of water solution of poloxamer 407, was investigated, and formulated systems were evaluated as carriers for percutaneous delivery of ibuprofen. Formulation study of pseudo-ternary system liquid lecithin/poloxamer 407/water at constant liquid lecithin/poloxamer 407 mass ratio (2.0) revealed that minimum concentrations of liquid lecithin and poloxamer 407 required for formation of gel like systems were 15.75% w/w and 13.13% w/w, respectively, while the maximum content of water was 60.62% w/w. The systems comprising water concentrations in a range from 55 to 60.62% w/w were soft semisolids suitable for topical application, and they were selected for physicochemical and biopharmaceutical evaluation. Analysis of conductivity results and light microscopy examination revealed that investigated systems were water dilutable dispersions of spherical oligolamellar associates of phospholipids and triglyceride molecules in the copolymer water solution. Rheological behavior evaluation results indicated that the investigated gels were thermosensitive shear thinning systems. Ibuprofen (5% w/w) was incorporated by dispersing into the previously prepared carriers. Drug-loaded systems were physically stable at storage temperature from 5 ± 3°C to 40 ± 2°C, for 30 days. In vitro ibuprofen release was in accordance with the Higuchi model (rH>0.95) and sustained for 12h. The obtained results implicated that formulated LLPBGs, optimized regarding drug release and organoleptic properties, represent promising carriers for sustained percutaneous drug delivery of poorly soluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Nanoparticle carriers based on copolymers of poly(l-aspartic acid co-l-lactide)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine for drug delivery

Energy Technology Data Exchange (ETDEWEB)

Han Siyuan; Wang Huan; Liang Xingjie [National Center for Nanoscience and Technology, Laboratory of Nanobiomedicine and Nanosafety, Division of Nanomedicine and Nanobiology (China); Hu Liming, E-mail: huliming@bjut.edu.cn [Beijing University of Technology, College of Life Science and Bioengineering (China); Li Min; Wu Yan, E-mail: wuy@nanoctr.cn [National Center for Nanoscience and Technology, Laboratory of Nanobiomedicine and Nanosafety, Division of Nanomedicine and Nanobiology (China)

2011-09-15

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 ({sup 1}H NMR, {sup 13}C NMR, {sup 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.

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.

Development of biodegradable polymer based tamoxifen citrate loaded nanoparticles and effect of some manufacturing process parameters on them: a physicochemical and in-vitro evaluation

Directory of Open Access Journals (Sweden)

Basudev Sahana

2010-08-01

Full Text Available Basudev Sahana, Kousik Santra, Sumit Basu, Biswajit MukherjeeDepartment of Pharmaceutical Technology, Jadavpur University, Kolkata, IndiaAbstract: The aim of the present study was to develop nanoparticles of tamoxifen citrate, a non-steroidal antiestrogenic drug used for the treatment of breast cancer. Biodegradable poly (D, L- lactide-co-glycolide-85:15 (PLGA was used to develop nanoparticles of tamoxifen citrate by multiple emulsification (w/o/w and solvent evaporation technique. Drug-polymer ratio, polyvinyl alcohol concentrations, and homogenizing speeds were varied at different stages of preparation to optimize the desired size and release profile of drug. The characterization of particle morphology and shape was performed by field emission scanning electron microscope (FE-SEM and particle size distribution patterns were studied by direct light scattering method using zeta sizer. In vitro drug release study showed that release profile of tamoxifen from biodegradable nanoparticles varied due to the change in speed of centrifugation for separation. Drug loading efficiency varied from 18.60% to 71.98%. The FE-SEM study showed that biodegradable nanoparticles were smooth and spherical in shape. The stability studies of tamoxifen citrate in the experimental nanoparticles showed the structural integrity of tamoxifen citrate in PLGA nanoparticles up to 60°C in the tested temperatures. Nanoparticles containing tamoxifen citrate could be useful for the controlled delivery of the drug for a prolonged period.Keywords: biodegradable, nanoparticles, PLGA, stability, tamoxifen citrate

Biodegradable congress 2012; Bioschmierstoff-Kongress 2012

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-11-01

Within the Guelzower expert discussions at 5th and 6th June, 2012 in Oberhausen (Federal Republic of Germany) the following lectures were held: (1) Promotion of biodegradable lubricants by means of research and development as well as public relations (Steffen Daebeler); (2) Biodegradable lubricants - An overview of the advantages and disadvantages of the engaged product groups (Hubertus Murrenhoff); (3) Standardization of biodegradable lubricants - CEN/DIN standard committees - state of the art (Rolf Luther); (4) Market research for the utilization of biodegradable lubricants and means of proof of sustainability (Norbert Schmitz); (5) Fields of application for high performance lubricants and requirements upon the products (Gunther Kraft); (6) Investigations of biodegradable lubricants in rolling bearings and gears (Christoph Hentschke); (7) Biodegradable lubricants in central lubrication systems Development of gears and bearings of offshore wind power installations (Reiner Wagner); (8) Investigations towards environmental compatibility of biodegradable lubricants used in offshore wind power installations (Tolf Schneider); (9) Development of glycerine based lubricants for the industrial metalworking (Harald Draeger); (10) Investigations and utilization of biodegradable oils as electroinsulation oils in transformers (Stefan Tenbohlen); (11) Operational behaviour of lubricant oils in vegetable oil operation and Biodiesel operation (Horst Hamdorf); (12) Lubrication effect of lubricating oil of the third generation (Stefan Heitzig); (13) Actual market development from the view of a producer of biodegradable lubricants (Frank Lewen); (14) Utilization of biodegradable lubricants in forestry harvesters (Guenther Weise); (15) New biodegradable lubricants based on high oleic sunflower oil (Otto Botz); (16) Integrated fluid concept - optimized technology and service package for users of biodegradable lubricants (Juergen Baer); (17) Utilization of a bio oil sensor to control

Herbal carrier-based floating microparticles of diltiazem ...

African Journals Online (AJOL)

Purpose: To formulate and characterize a gastroretentive floating drug delivery system for diltiazem hydrochloride using psyllium husk and sodium alginate as natural herbal carriers to improve the therapeutic effect of the drug in cardiac patients. Methods: Floating microparticles containing diltiazem hydrochloride were ...

Nano-cellulose based nano-coating biomaterial dataset using corn leaf biomass: An innovative biodegradable plant biomaterial

Directory of Open Access Journals (Sweden)

A.B.M. Sharif Hossain

2018-04-01

Full Text Available The nanocellulose derived biodegradable plant biomaterial as nano-coating can be used in the medical, biomedical cosmetics, and bioengineering products. Bio-plastic and some synthetic derived materials are edible and naturally biodegradable. The study was conducted to investigate edible nano-biopolymer based nano-coating of capsules and drugs or other definite biomedical materials from corn leaf biomass. Corn leaf biomass was used as an innovative sample to produce edible nano-coating bioplastic for drug and capsule coating and other industrial uses. The data show the negligible water 0.01% absorbed by bio-plastic nanocoating. Odor represented by burning test was under the completely standard based on ASTM. Moreover, data on color coating, tensile strength, pH, cellulose content have been shown under standard value of ASTM (American standard for testing and materials standard. In addition to that data on the chemical element test like K+, CO3−−, Cl-, Na+ exhibited positive data compared to the synthetic plastic in the laboratory using the EN (166 standardization. Therefore, it can be concluded that both organic (cellulose and starch based edible nano-coating bioplastic may be used for drug and capsule coating as biomedical and medical components in the pharmaceutical industries. Keywords: Nanocellulose, Nanobioplastic, Nanocoating, Biodegradable, Corn leaf

Transforming lipid-based oral drug delivery systems into solid dosage forms: an overview of solid carriers, physicochemical properties, and biopharmaceutical performance.

Science.gov (United States)

Tan, Angel; Rao, Shasha; Prestidge, Clive A

2013-12-01

The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.

ANAEROBIC BIODEGRADATION OF A BIODEGRADABLE MATERIAL UNDER ANAEROBIC - THERMOPHILIC DIGESTION

Directory of Open Access Journals (Sweden)

RICARDO CAMACHO-MUÑOZ

2014-12-01

Full Text Available This paper dertermined the anaerobic biodegradation of a polymer obtained by extrusion process of native cassava starch, polylactic acid and polycaprolactone. Initially a thermophilic - methanogenic inoculum was prepared from urban solid waste. The gas final methane concentration and medium’s pH reached values of 59,6% and 7,89 respectively. The assay assembly was carried out according ASTM D5511 standard. The biodegradation percent of used materials after 15 day of digestion were: 77,49%, 61,27%, 0,31% for cellulose, sample and polyethylene respectively. Due cellulose showed biodegradation levels higher than 70% it’s deduced that the inoculum conditions were appropriate. A biodegradation level of 61,27%, 59,35% of methane concentration in sample’s evolved gas and a medium’s finale pH of 7,71 in sample’s vessels, reveal the extruded polymer´s capacity to be anaerobically degraded under thermophilic- high solid concentration conditions.

External validation of structure-biodegradation relationship (SBR) models for predicting the biodegradability of xenobiotics.

Science.gov (United States)

Devillers, J; Pandard, P; Richard, B

2013-01-01

Biodegradation is an important mechanism for eliminating xenobiotics by biotransforming them into simple organic and inorganic products. Faced with the ever growing number of chemicals available on the market, structure-biodegradation relationship (SBR) and quantitative structure-biodegradation relationship (QSBR) models are increasingly used as surrogates of the biodegradation tests. Such models have great potential for a quick and cheap estimation of the biodegradation potential of chemicals. The Estimation Programs Interface (EPI) Suite™ includes different models for predicting the potential aerobic biodegradability of organic substances. They are based on different endpoints, methodologies and/or statistical approaches. Among them, Biowin 5 and 6 appeared the most robust, being derived from the largest biodegradation database with results obtained only from the Ministry of International Trade and Industry (MITI) test. The aim of this study was to assess the predictive performances of these two models from a set of 356 chemicals extracted from notification dossiers including compatible biodegradation data. Another set of molecules with no more than four carbon atoms and substituted by various heteroatoms and/or functional groups was also embodied in the validation exercise. Comparisons were made with the predictions obtained with START (Structural Alerts for Reactivity in Toxtree). Biowin 5 and Biowin 6 gave satisfactorily prediction results except for the prediction of readily degradable chemicals. A consensus model built with Biowin 1 allowed the diminution of this tendency.

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.

Sustained release of antibiotics from injectable and thermally responsive polypeptide depots.

Science.gov (United States)

Adams, Samuel B; Shamji, Mohammed F; Nettles, Dana L; Hwang, Priscilla; Setton, Lori A

2009-07-01

Biodegradable polymeric scaffolds are of interest for delivering antibiotics to local sites of infection in orthopaedic applications, such as bone and diarthrodial joints. The objective of this study was to develop a biodegradable scaffold with ease of drug loading in aqueous solution, while providing for drug depot delivery via syringe injection. Elastin-like polypeptides (ELPs) were used for this application, biopolymers of repeating pentapeptide sequences that were thermally triggered to undergo in situ depot formation at body temperature. ELPs were modified to enable loading with the antibiotics, cefazolin, and vancomycin, followed by induction of the phase transition in vitro. Cefazolin and vancomycin concentrations were monitored, as well as bioactivity of the released antibiotics, to test an ability of the ELP depot to provide for prolonged release of bioactive drugs. Further tests of formulation viscosity were conducted to test suitability as an injectable drug carrier. Results demonstrate sustained release of therapeutic concentrations of bioactive antibiotics by the ELP, with first-order time constants for drug release of approximately 25 h for cefazolin and approximately 500 h for vancomycin. These findings illustrate that an injectable, in situ forming ELP depot can provide for sustained release of antibiotics with an effect that varies across antibiotic formulation. ELPs have important advantages for drug delivery, as they are known to be biocompatible, biodegradable, and elicit no known immune response. These benefits suggest distinct advantages over currently used carriers for antibiotic drug delivery in orthopedic applications. (c) 2008 Wiley Periodicals, Inc.

Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review

Directory of Open Access Journals (Sweden)

Islam MA

2012-12-01

Full Text Available Mohammad Ariful Islam,1–3,* Jannatul Firdous,1–3,* Yun-Jaie Choi,1 Cheol-Heui Yun,1–4 Chong-Su Cho1,21Department of Agricultural Biotechnology, 2Research Institute for Agriculture and Life Sciences, 3Center for Food and Bioconvergence, 4World Class University Biomodulation Program, Seoul National University, Seoul, South Korea*These authors contributed equally to this workAbstract: Chitosan, a natural biodegradable polymer, is of great interest in biomedical research due to its excellent properties including bioavailability, nontoxicity, high charge density, and mucoadhesivity, which creates immense potential for various pharmaceutical applications. It has gelling properties when it interacts with counterions such as sulfates or polyphosphates and when it crosslinks with glutaraldehyde. This characteristic facilitates its usefulness in the coating or entrapment of biochemicals, drugs, antigenic molecules as a vaccine candidate, and microorganisms. Therefore, chitosan together with the advance of nanotechnology can be effectively applied as a carrier system for vaccine delivery. In fact, chitosan microspheres have been studied as a promising carrier system for mucosal vaccination, especially via the oral and nasal route to induce enhanced immune responses. Moreover, the thiolated form of chitosan is of considerable interest due to its improved mucoadhesivity, permeability, stability, and controlled/extended release profile. This review describes the various methods used to design and synthesize chitosan microspheres and recent updates on their potential applications for oral and nasal delivery of vaccines. The potential use of thiolated chitosan microspheres as next-generation mucosal vaccine carriers is also discussed.Keywords: chitosan microspheres, oral, nasal, vaccine delivery, mucosal and systemic immune responses

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

Biodegradation of selected offshore chemicals

OpenAIRE

Wennberg, Aina C.; Petersen, Karina

2017-01-01

A review of biodegradation data for specific oil field chemicals and chemical groups were performed in order to evaluate if the current categorisation of these were appropriate based on the biodegradation properties. Data were compiled from databases like ECHA and MITI and from the literature. For compounds with limited or inconclusive test data, biodegradation was also estimated by the BIOWIN models, and the EAWAG-BBD pathway prediction system was used to predict plausible biodegradation pat...

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

Science.gov (United States)

Wang, Xue-Qing; Zhang, Qiang

2012-10-01

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

Investigation into Alternative Sugars as Potential Carriers for Dry Powder Formulation of Budesonide

Directory of Open Access Journals (Sweden)

Ali Nokhodchi

2011-08-01

Full Text Available Introduction: Dry powder inhaler (DPI formulations are so far being used for pulmonary drug delivery, mainly for the treatment of asthma and chronic obstructive pulmonary disease (COPD. Currently most of DPI formulations rely on lactose as a carrier in the drug powder blend. However, due to reducing sugar function of lactose which makes it incompatible with some drugs such as budesonide, it is realistic to investigate for alternative sugars that would overcome the concerned drawback but still have the positive aspects of lactose. Methods: The study was conducted by characterizing carriers for their physico-chemical properties and preparing drug/carrier blends with concentration of 5% and 10% drug with the carrier. The mixing uniformity (homogeneity of Budesonide in the blends was analyzed using spectrophotometer. The blend was then filled into NB7/2 Airmax inhaler device and the deposition profiles of the drug were determined using multi stage liquid impinger (MSLI after aerosolization at 4 kPa via the inhaler. The morphology of the carriers conducted using the scanning electron microscope. Results: The results determined that the mean fine particle fraction (FPF of 5% and 10% blends of mannitol was 61%, possibly due to fine elongated particles. Dextrose exhibited excellent flowability. Scanning electron microscope illustrated mannitol with fine elongated particles and dextrose presenting larger and coarse particles. It was found out that type of carriers, particle size distribution, and morphology would influence the FPF of budesonide. Conclusion: It may be concluded that mannitol could be suitable as a carrier on the basis of its pharmaceutical performance and successful achievement of FPF whereas the more hygroscopic sugars such as sorbitol or xylitol showed poor dispersibility leading to lower FPF.

Comparative study on the biodegradation and biocompatibility of silicate bioceramic coatings on biodegradable magnesium alloy as biodegradable biomaterial

Science.gov (United States)

Razavi, M.; Fathi, M. H.; Savabi, O.; Razavi, S. M.; Hashemibeni, B.; Yazdimamaghani, M.; Vashaee, D.; Tayebi, L.

2014-03-01

Many clinical cases as well as in vivo and in vitro assessments have demonstrated that magnesium alloys possess good biocompatibility. Unfortunately, magnesium and its alloys degrade too quickly in physiological media. In order to improve the biodegradation resistance and biocompatibility of a biodegradable magnesium alloy, we have prepared three types of coating include diopside (CaMgSi2O6), akermanite (Ca2MgSi2O6) and bredigite (Ca7MgSi4O16) coating on AZ91 magnesium alloy through a micro-arc oxidation (MAO) and electrophoretic deposition (EPD) method. In this research, the biodegradation and biocompatibility behavior of samples were evaluated in vitro and in vivo. The in vitro analysis was performed by cytocompatibility and MTT-assay and the in vivo test was conducted on the implantation of samples in the greater trochanter of adult rabbits. The results showed that diopside coating has the best bone regeneration and bredigite has the best biodegradation resistance compared to others.

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

P-glycoprotein targeted nanoscale drug carriers

KAUST Repository

Li, Wengang; Abu Samra, Dina Bashir Kamil; Merzaban, Jasmeen; Khashab, Niveen M.

2013-01-01

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

Use Of Biodegradation Ratios In Monitoring Trend Of Biostimulated Biodegradation In Crude Oil Polluted Soils

Directory of Open Access Journals (Sweden)

Okorondu

2017-03-01

Full Text Available This study deals with biodegradation experiment on soil contaminated with crude oil. The soil sample sets A BC D E F G were amended with inorganic fertilizer to enhance microbial growth and hydrocarbon degradation moisture content of some of the sets were as well varied. Biodegradation ratios nC17Pr nC18Ph and nC17nC18PrPh were used to monitor biodegradation of soil sets A BC D E F G for a period of 180. The soil samples were each contaminated with the same amount of crude oil and exposed to specific substrate treatment regarding the amount of nutrients and water content over the same period of time. The trend in biodegradation of the different soil sample sets shows that biodegradation ratio nC17nC18PrPh was more reflective of and explains the biodegradation trend in all the sample sets throughout the period of the experiment hence a better parameter ratio for monitoring trend of biostimulated biodegradation. The order of preference of the biodegradation ratios is expressed as nC18Ph nC17Pr nC17nC18 PrPh. This can be a relevant support tool when designing bioremediation plan on field.

Sugarcane bagasse lignin, and silica gel and magneto-silica as drug vehicles for development of innocuous methotrexate drug against rheumatoid arthritis disease in albino rats

International Nuclear Information System (INIS)

Wahba, Sanaa M.R.; Darwish, Atef S.; Shehata, Iman H.; Abd Elhalem, Sahar S.

2015-01-01

The present study clarifies co-therapy action of deliveries from their textural changes point of view. Methotrexate (MTX) was immobilized onto biodegradable lignin, silica gel and iron/silica nanocomposite. Loaded-MTX was i.p. injected into albino rats at doses of 0.25 and 0.5 mg/kg/week for 2.5 months, after which spleen, liver, testes and knee joint tissues were collected for tests. IFN-γ and IL-17A mRNA gene expressions in spleen in all biological samples were determined by RT-PCR. Physicochemical features of drug carriers were monitored by XRD, BET-PSD, SEM and TEM. Drug inflammatory-site targeting was found to be closely related to the physico-features of deliverers. The interlayered lignin of micro- and meso-pore channels directed MTX toward concealed infected cells in liver and testes tissues, while meso-structured silica flacks satisfied by gathering MTX around knee joints. The magneto-silica nanocomposite targeted MTX toward spleen tissue, which is considered as a lively factory for the production of electron rich compounds. - Highlights: • Opening the door to synthesize smart targeted drug deliveries against RA disease • Therapy action of MTX-laden lignin and Fe 3 O 4 /SiO 2 composite toward RA disease • Procure selective targeted drug deliveries of near 100% curing against RA disease • Revolutionary clinical therapies for RA disease by inventive MTX-delivery models

Improving Dry Powder Inhaler Performance by Surface Roughening of Lactose Carrier Particles.

Science.gov (United States)

Tan, Bernice Mei Jin; Chan, Lai Wah; Heng, Paul Wan Sia

2016-08-01

This study investigated the impact of macro-scale carrier surface roughness on the performance of dry powder inhaler (DPI) formulations. Fluid-bed processing and roller compaction were explored as processing methods to increase the surface roughness (Ra) of lactose carrier particles. DPI formulations containing either (a) different concentrations of fine lactose at a fixed concentration of micronized drug (isoniazid) or (b) various concentrations of drug in the absence of fine lactose were prepared. The fine particle fraction (FPF) and aerodynamic particle size of micronized drug of all formulations were determined using the Next Generation Impactor. Fluid-bed processing resulted in a modest increase in the Ra from 562 to 907 nm while roller compaction led to significant increases in Ra > 1300 nm. The roller compacted carriers exhibited FPF > 35%, which were twice that of the smoothest carriers. The addition of up to 5%, w/w of fine lactose improved the FPF of smoother carriers by 60-200% whereas only lactose carrier particles by roller compaction was immensely beneficial to improving DPI performance, primarily due to increased surface roughness at the macro-scale.

Preparation and drug controlled release of porous octyl-dextran microspheres.

Science.gov (United States)

Hou, Xin; Liu, Yanfei

2015-01-01

In this work, porous octyl-dextran microspheres with excellent properties were prepared by two steps. Firstly, dextran microspheres were synthesized by reversed-phase suspension polymerization. Secondly, octyl-dextran microspheres were prepared by the reaction between dextran microspheres and ethylhexyl glycidyl ether and freezing-drying method. Porous structure of microspheres was formed through the interaction between octyl groups and organic solvents. The structure, morphology, dry density, porosity and equilibrium water content of porous octyl-dextran microspheres were systematically investigated. The octyl content affected the properties of microspheres. The results showed that the dry density of microspheres decreased from 2.35 to 1.21 g/ml, porosity increased from 80.68 to 95.05% with the octyl content increasing from 0.49 to 2.28 mmol/g. Meanwhile, the equilibrium water content presented a peak value (90.18%) when the octyl content was 2.25 mmol/g. Octyl-dextran microspheres showed high capacity. Naturally drug carriers play an important role in drug-delivery systems for their biodegradability, wide raw materials sources and nontoxicity. Doxorubicin (DOX) was used as a drug model to examine the drug-loading capacity of porous octyl-dextran microspheres. The drug-loading efficiency increased with the increase in microspheres/drug ratio, while the encapsulation efficiency decreased. When microspheres/drug mass ratio was 4/1, the drug-loading efficiency and encapsulation efficiency were 10.20 and 51.00%, respectively. The release rate of DOX increased as drug content and porosity increased. In conclusion, porous octyl-dextran microspheres were synthesized successfully and have the potential to serve as an effective delivery system in drug controlled release.

Solute carrier transporters: Pharmacogenomics research ...

African Journals Online (AJOL)

Aghogho

2010-12-27

Dec 27, 2010 ... This paper reviews the solute carrier transporters and highlights the fact that there is much to be learnt from .... transporters, drug targets, effect or proteins and meta- ... basolateral or apical plasma membrane of polarized cells,.

Phthalates biodegradation in the environment.

Science.gov (United States)

Liang, Da-Wei; Zhang, Tong; Fang, Herbert H P; He, Jianzhong

2008-08-01

Phthalates are synthesized in massive amounts to produce various plastics and have become widespread in environments following their release as a result of extensive usage and production. This has been of an environmental concern because phthalates are hepatotoxic, teratogenic, and carcinogenic by nature. Numerous studies indicated that phthalates can be degraded by bacteria and fungi under aerobic, anoxic, and anaerobic conditions. This paper gives a review on the biodegradation of phthalates and includes the following aspects: (1) the relationship between the chemical structure of phthalates and their biodegradability, (2) the biodegradation of phthalates by pure/mixed cultures, (3) the biodegradation of phthalates under various environments, and (4) the biodegradation pathways of phthalates.

Controllable fabrication and characterization of biocompatible core-shell particles and hollow capsules as drug carrier

Science.gov (United States)

Hao, Lingyun; Gong, Xinglong; Xuan, Shouhu; Zhang, Hong; Gong, Xiuqing; Jiang, Wanquan; Chen, Zuyao

2006-10-01

SiO 2@CdSe core-shell particles were fabricated by controllable deposition CdSe nanoparticles on silica colloidal spheres. Step-wise coating process was tracked by the TEM and XRD measurements. In addition, SiO 2@CdSe/polypyrrole(PPy) multi-composite particles were synthesized based on the as-prepared SiO 2@CdSe particles by cationic polymerization. The direct electrochemistry of myoglobin (Mb) could be performed by immobilizing Mb on the surface of SiO 2@CdSe particles. Immobilized with Mb, SiO 2@CdSe/PPy-Mb also displayed good bioelectrochemical activity. It confirmed the good biocompatible property of the materials with protein. CdSe hollow capsules were further obtained as the removal of the cores of SiO 2@CdSe spheres. Hollow and porous character of CdSe sub-meter size capsules made them becoming hopeful candidates as drug carriers. Doxorubicin, a typical an antineoplastic drug, was introduced into the capsules. A good sustained drug release behavior of the loading capsules was discovered via performing a release test in the PBS buffer (pH 7.4) solution at 310 k. Furthermore, SiO 2@CdSe/PPy could be converted to various smart hollow capsules via selectively removal of their relevant components.

A review of plastic waste biodegradation.

Science.gov (United States)

Zheng, Ying; Yanful, Ernest K; Bassi, Amarjeet S

2005-01-01

With more and more plastics being employed in human lives and increasing pressure being placed on capacities available for plastic waste disposal, the need for biodegradable plastics and biodegradation of plastic wastes has assumed increasing importance in the last few years. This review looks at the technological advancement made in the development of more easily biodegradable plastics and the biodegradation of conventional plastics by microorganisms. Additives, such as pro-oxidants and starch, are applied in synthetic materials to modify and make plastics biodegradable. Recent research has shown that thermoplastics derived from polyolefins, traditionally considered resistant to biodegradation in ambient environment, are biodegraded following photo-degradation and chemical degradation. Thermoset plastics, such as aliphatic polyester and polyester polyurethane, are easily attacked by microorganisms directly because of the potential hydrolytic cleavage of ester or urethane bonds in their structures. Some microorganisms have been isolated to utilize polyurethane as a sole source of carbon and nitrogen source. Aliphatic-aromatic copolyesters have active commercial applications because of their good mechanical properties and biodegradability. Reviewing published and ongoing studies on plastic biodegradation, this paper attempts to make conclusions on potentially viable methods to reduce impacts of plastic waste on the environment.

Genipin-cross-linked poly(L-lysine)-based hydrogels: synthesis, characterization, and drug encapsulation.

Science.gov (United States)

Wang, Steven S S; Hsieh, Ping-Lun; Chen, Pei-Shan; Chen, Yu-Tien; Jan, Jeng-Shiung

2013-11-01

Genipin-cross-linked hydrogels composed of biodegradable and pH-sensitive cationic poly(L-lysine) (PLL), poly(L-lysine)-block-poly(L-alanine) (PLL-b-PLAla), and poly(L-lysine)-block-polyglycine (PLL-b-PGly) polypeptides were synthesized, characterized, and used as carriers for drug delivery. These polypeptide hydrogels can respond to pH-stimulus and their gelling and mechanical properties, degradation rate, and drug release behavior can be tuned by varying polypeptide composition and cross-linking degree. Comparing with natural polymers, the synthetic polypeptides with well-defined chain length and composition can warrant the preparation of the hydrogels with tunable properties to meet the criteria for specific biomedical applications. These hydrogels composed of natural building blocks exhibited good cell compatibility and enzyme degradability and can support cell attachment/proliferation. The evaluation of these hydrogels for in vitro drug release revealed that the controlled release profile was a biphasic pattern with a mild burst release and a moderate release rate thereafter, suggesting the drug molecules were encapsulated inside the gel matrix. With the versatility of polymer chemistry and conjugation of functional moieties, it is expected these hydrogels can be useful for biomedical applications such as polymer therapeutics and tissue engineering. Copyright © 2013 Elsevier B.V. All rights reserved.

Copper-gold nanoparticles: Fabrication, characteristic and application as drug carriers

Energy Technology Data Exchange (ETDEWEB)

Woźniak-Budych, Marta J., E-mail: marta.budych@amu.edu.pl; Langer, Krzysztof; Peplińska, Barbara; Przysiecka, Łucja; Jarek, Marcin; Jarzębski, Maciej; Jurga, Stefan

2016-08-15

In this investigation, the fabrication of porous core/shell nanostructures consisting of copper (core) and copper-gold nanoalloy (shell) for medical applications is presented. As a core triangular-shaped copper nanoparticles were used. The porous bimetallic nanoshell was prepared via galvanic reaction in the presence of oil-in water emulsion. It was proved that porous nanoalloy layer can be prepared at pH 7 and in the presence 0.1% and 0.5% oil-in water emulsion. The porous structure fabrication was mainly determined by volume fraction of hexadecane to acetone in the oil-in water emulsion and Zeta-potential of emulsion droplets (pH of emulsion). The influence of emulsion droplets size before galvanic reaction on porous structure preparation was negligible. It was found that doxorubicin could be easily introduced and released from porous core/shell nanostructures, due to spontaneous adsorption on the copper-gold nanoporous surface. The in vitro test showed that cytotoxic effect was more prominent once the doxorubicin was adsorbed on the porous copper-gold nanocarriers. It was demonstrated, that doxorubicin-loaded copper-gold nanostructures caused inhibition cell proliferation and viability of cancer cells, in a concentration-dependent manner. The results indicates that presented coper-gold nanocarrier have potential to be used in targeted cancer therapy, due to its porous structure and cytotoxic effect in cancer cells. - Highlights: • Porous copper-gold nanostructure as a cytostatic drug carrier was prepared. • Kinetics and thermodynamics of drug adsorption were studied. • DOX-loaded copper-gold nanoparticles showed a pH-controlled release rate. • DOX-loaded copper-gold NPs caused inhibition cell proliferation of cancer cells. • The Cu-Au NPs could serve as a theranostic platform for biomedical applications.

Influence of PCL on the material properties of collagen based biocomposites and in vitro evaluation of drug release

International Nuclear Information System (INIS)

Kanungo, Ivy; Fathima, Nishter Nishad; Rao, Jonnalagadda Raghava; Nair, Balachandran Unni

2013-01-01

Formulation of biodegradable collagen–poly-ε-caprolactone (PCL) based biomaterials for the sustained release of insulin is the main objective of the present work. PCL has been employed to modulate the physico-chemical behavior of collagen to control the drug release. Designed formulations were employed to statistically optimize insulin release parameter profile at different collagen to PCL molar ratios. Circular dichroism, thermoporometry, FTIR, impedance and scanning electron microscopy techniques have been employed to investigate the effect of PCL on hydration dynamics of the collagen molecule, which in turn changes the dissolution parameters of the drug from the systems. Drug entrapment efficiency has been found to be maximum for collagen to PCL molar ratio of 1:2 (> 90%). In vitro dissolution test reveals that 99% of the drug was released from composite at collagen to PCL molar ratio of 1:3 and 1:4 within 2 h, which indicates that hydrophobicity of the matrix results in weak interaction between lipophilic drug and carrier materials. The least burst release was observed for collagen to PCL molar ratio at 1:2 as synergistic interactions between collagen and PCL was maximum at that particular polymer–polymer ratios. The drug release data indicates super case-II transport of drug (n > 1.0). - Graphical abstract: Collagen–poly-ε-caprolactone based biomaterials for the sustained release of insulin were formulated. Circular dichroism, thermoporometry, FTIR, impedance and scanning electron microscopy techniques have been employed to elucidate the effect of PCL on the structure of the collagen and in vitro drug release. The drug release data fitted to the kinetic model indicates super case-II transport due to the combination of diffusion and polymer relaxation/dissolution (n > 1.0). - Highlights: • Poly-ε-caprolactone influences physico-chemical behavior of collagen. • Poly-ε-caprolactone influences in vitro drug release mechanism from biocomposites. �

Comparison of Durable-Polymer Zotarolimus-Eluting and Biodegradable-Polymer Biolimus-Eluting Coronary Stents in Patients With Coronary Artery Disease

DEFF Research Database (Denmark)

Raungaard, Bent; Christiansen, Evald H; Bøtker, Hans Erik

2017-01-01

artery disease or acute coronary syndromes and at least 1 coronary artery lesion requiring treatment with a drug-eluting stent. Endpoints included major adverse cardiac events (MACE), a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion......OBJECTIVES: The authors sought to compare the safety and efficacy of the biocompatible durable-polymer zotarolimus-eluting stent with the biodegradable-polymer biolimus-eluting stent in unselected coronary patients. BACKGROUND: Biodegradable-polymer biolimus-eluting stents are superior to first......-generation durable-polymer drug-eluting stents in long-term randomized all-comer trials. Long-term data comparing them to second-generation durable-polymer drug-eluting stents are lacking. METHODS: The study was a randomized, multicenter, all-comer, noninferiority trial in patients with chronic stable coronary...

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

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

Recent Advances in Ocular Drug Delivery Systems

Directory of Open Access Journals (Sweden)

Shinobu Fujii

2011-01-01

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

External validation of EPIWIN biodegradation models.

Science.gov (United States)

Posthumus, R; Traas, T P; Peijnenburg, W J G M; Hulzebos, E M

2005-01-01

The BIOWIN biodegradation models were evaluated for their suitability for regulatory purposes. BIOWIN includes the linear and non-linear BIODEG and MITI models for estimating the probability of rapid aerobic biodegradation and an expert survey model for primary and ultimate biodegradation estimation. Experimental biodegradation data for 110 newly notified substances were compared with the estimations of the different models. The models were applied separately and in combinations to determine which model(s) showed the best performance. The results of this study were compared with the results of other validation studies and other biodegradation models. The BIOWIN models predict not-readily biodegradable substances with high accuracy in contrast to ready biodegradability. In view of the high environmental concern of persistent chemicals and in view of the large number of not-readily biodegradable chemicals compared to the readily ones, a model is preferred that gives a minimum of false positives without a corresponding high percentage false negatives. A combination of the BIOWIN models (BIOWIN2 or BIOWIN6) showed the highest predictive value for not-readily biodegradability. However, the highest score for overall predictivity with lowest percentage false predictions was achieved by applying BIOWIN3 (pass level 2.75) and BIOWIN6.

Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer

Directory of Open Access Journals (Sweden)

Liang Y

2017-03-01

Full Text Available Yan Liang,1 Baocheng Tian,1 Jing Zhang,1 Keke Li,1 Lele Wang,1 Jingtian Han,1,* Zimei Wu2,* 1School of Pharmacy, Binzhou Medical University, 2School of Pharmacy, Yantai University, Yantai, China *These authors contributed equally to this work Abstract: Gemcitabine (GEM and paclitaxel (PTX are effective combination anticancer agents against non-small-cell lung cancer (NSCLC. At the present time, a main challenge of combination treatment is the precision of control that will maximize the combined effects. Here, we report a novel method to load GEM (hydrophilic and PTX (hydrophobic into simplex tumor-targeted nanostructured lipid carriers (NLCs for accurate control of the ratio of the two drugs. We covalently preconjugated the dual drugs through a hydrolyzable ester linker to form drug conjugates. N-acetyl-D-glucosamine (NAG is a glucose receptor-targeting ligand. We added NAG to the formation of NAG-NLCs. In general, synthesis of poly(6-O-methacryloyl-d-galactopyranose–GEM/PTX (PMAGP-GEM/PTX conjugates was demonstrated, and NAG-NLCs were prepared using emulsification and solvent evaporation. NAG-NLCs displayed sphericity with an average diameter of 120.3±1.3 nm, a low polydispersity index of 0.233±0.04, and accurate ratiometric control over the two drugs. A cytotoxicity assay showed that the NAG-NLCs had better antitumor activity on NSCLC cells than normal cells. There was an optimal ratio of the two drugs, exhibiting the best cytotoxicity and combinatorial effects among all the formulations we tested. In comparison with both the free-drug combinations and separately nanopackaged drug conjugates, PMAGP-GEM/PTX NAG-NLCs (3:1 exhibited superior synergism. Flow cytometry and confocal laser scanning microscopy showed that NAG-NLCs exhibited higher uptake efficiency in A549 cells via glucose receptor-mediated endocytosis. This combinatorial delivery system settles problems with ratiometric coloading of hydrophilic and hydrophobic drugs for tumor

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.

Solubility and dissolution enhancement of flurbiprofen by solid dispersion using hydrophilic carriers

Directory of Open Access Journals (Sweden)

Bhaskar Daravath

2018-05-01

Full Text Available ABSTRACT The intent of the current work is to study the effect of polyethylene glycol 8000 and polyethylene glycol 10000 as hydrophilic carriers on dissolution behaviour of flurbiprofen. In the present study, solvent evaporation method was used to prepare flurbiprofen solid dispersions and evaluated for physico-chemical properties, drug-carrier compatibility studies and dissolution behaviour of drug. Solubility studies showed more solubility in higher pH values and formulations SD4 and SD8 were selected to prepare the fast dissolving tablets. FTIR and DSC study showed no interaction and drug was dispersed molecularly in hydrophilic carrier. XRD studies revealed that there was change in the crystallinity of the drug. The results of In vitro studies showed SD8 formulation confer significant improvement (p<0.05 in drug release, Q20 was 99.08±1.35% compared to conventional and marketed tablets (47.31±0.74% and 56.86±1.91%. The mean dissolution time (MDT was reduced to 8.79 min compared to conventional and marketed tablets (25.76 and 22.22 min. indicating faster drug release. The DE (% dissolution efficiency was increased by 2.5 folds (61.63% compared to conventional tablets (23.71%. From the results, it is evident that polyethylene glycol solid dispersions in less carrier ratio may enhance the solubility and there by improve the dissolution rate of flurbiprofen.

Biodegradation of lubricant oil

African Journals Online (AJOL)

M

2012-09-25

Sep 25, 2012 ... lubricating oil, showed high biodegradation efficiency for different used lubricating oils. Capability of ..... amount after biodegradation showed no difference in the .... products polluted sites in Elele, Rivers State, Ngeria.

Crossing the Blood-Brain Barrier: Recent Advances in Drug Delivery to the Brain.

Science.gov (United States)

Patel, Mayur M; Patel, Bhoomika M

2017-02-01

CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting. Several approaches have been investigated to allow therapeutics to cross the BBB. As the molecular structure of the BBB is better elucidated, several key approaches for brain targeting include physiological transport mechanisms such as adsorptive-mediated transcytosis, inhibition of active efflux pumps, receptor-mediated transport, cell-mediated endocytosis, and the use of peptide vectors. Drug-delivery approaches comprise delivery from microspheres, biodegradable wafers, and colloidal drug-carrier systems (e.g., liposomes, nanoparticles, nanogels, dendrimers, micelles, nanoemulsions, polymersomes, exosomes, and quantum dots). The current review discusses the latest advancements in these approaches, with a major focus on articles published in 2015 and 2016. In addition, we also cover the alternative delivery routes, such as intranasal and convection-enhanced diffusion methods, and disruption of the BBB for brain targeting.

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.

HPMA copolymer-drug conjugates with controlled tumor-specific drug release

Czech Academy of Sciences Publication Activity Database

Chytil, Petr; Koziolová, Eva; Etrych, Tomáš; Ulbrich, Karel

2018-01-01

Roč. 18, č. 1 (2018), s. 1-15, č. článku 1700209. ISSN 1616-5187 R&D Projects: GA ČR(CZ) GA15-02986S; GA ČR(CZ) GA17-13283S; GA ČR(CZ) GA17-08084S; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : biodegradable spacer * controlled drug release * drug delivery systems Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 3.238, year: 2016

Enhanced Cellular Uptake of Albumin-Based Lyophilisomes when Functionalized with Cell-Penetrating Peptide TAT in HeLa Cells

NARCIS (Netherlands)

van Bracht, Etienne; Versteegden, Luuk R. M.; Stolle, Sarah; Verdurmen, Wouter P. R.; Woestenenk, Rob; Raave, Rene; Hafmans, Theo; Oosterwijk, Egbert; Brock, Roland; van Kuppevelt, Toin H.; Daamen, Willeke F.

2014-01-01

Lyophilisomes are a novel class of biodegradable proteinaceous nano/micrometer capsules with potential use as drug delivery carrier. Cell-penetrating peptides (CPPs) including the TAT peptide have been successfully implemented for intracellular delivery of a broad variety of cargos including various

Polypeptide nanogels with hydrophobic moieties in the cross-linked ionic cores: Synthesis, characterization and implications for anticancer drug delivery

Science.gov (United States)

Kim, Jong Oh; Oberoi, Hardeep S.; Desale, Swapnil; Kabanov, Alexander V.; Bronich, Tatiana K.

2014-01-01

Polymer nanogels have gained considerable attention as a potential platform for drug delivery applications. Here we describe the design and synthesis of novel polypeptide-based nanogels with hydrophobic moieties in the cross-linked ionic cores. Diblock copolymer, poly(ethylene glycol)-b-poly(L-glutamic acid), hydrophobically modified with L-phenylalanine methyl ester moieties was used for controlled template synthesis of nanogels with small size (ca. 70 nm in diameter) and narrow particle size distribution. Steady-state and time-resolved fluorescence studies using coumarin C153 indicated the existence of hydrophobic domains in the ionic cores of the nanogels. Stable doxorubicin-loaded nanogels were prepared at high drug capacity (30 w/w%). We show that nanogels are enzymatically-degradable leading to accelerated drug release under simulated lysosomal acidic pH. Furthermore, we demonstrate that the nanogel-based formulation of doxorubicin is well tolerated and exhibit an improved antitumor activity compared to a free doxorubicin in an ovarian tumor xenograft mouse model. Our results signify the point to a potential of these biodegradable nanogels as attractive carriers for delivery of chemotherapeutics. PMID:23998716

A novel oral delivery system consisting in "drug-in cyclodextrin-in nanostructured lipid carriers" for poorly water-soluble drug: vinpocetine.

Science.gov (United States)

Lin, Congcong; Chen, Fen; Ye, Tiantian; Zhang, Lina; Zhang, Wenji; Liu, Dandan; Xiong, Wei; Yang, Xinggang; Pan, Weisan

2014-04-25

The purpose of this study was to develop a new delivery system based on drug cyclodextrin (CD) complexation and loading into nanostructured lipid carriers (NLC) to improve the oral bioavailability of vinpocetine (VP). Three different CDs and three different methods to obtain solid vinpocetine-cyclodextrin-tartaric acid complexes (VP-CD-TA) were contrasted. The co-evaporation vinpocetine-β-cyclodextrin-tartaric acid loaded NLC (VP-β-CD-TA COE-loaded NLC) was obtained by emulsification ultrasonic dispersion method. VP-β-CD-TA COE-loaded NLC was suitably characterized for particle size, polydispersity index, zeta potential, entrapment efficiency and the morphology. The crystallization of drug in VP-CD-TA and NLC was investigated by differential scanning calorimetry (DSC). The in vitro release study was carried out at pH 1.2, pH 6.8 and pH 7.4 medium. New Zealand rabbits were applied to investigate the pharmacokinetic behavior in vivo. The VP-β-CD-TA COE-loaded NLC presented a superior physicochemical property and selected to further study. In the in vitro release study, VP-β-CD-TA COE-loaded NLC exhibited a higher dissolution rate in the pH 6.8 and pH 7.4 medium than VP suspension and VP-NLC. The relative bioavailability of VP-β-CD-TA COE-loaded NLC was 592% compared with VP suspension and 92% higher than VP-NLC. In conclusion, the new formulation significantly improved bioavailability of VP for oral delivery, demonstrated a perspective way for oral delivery of poorly water-soluble drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Assessment of the biodegradability of selected sulfa drugs in two polluted rivers in Poland: Effects of seasonal variations, accidental contamination, turbidity and salinity.

Science.gov (United States)

Adamek, Ewa; Baran, Wojciech; Sobczak, Andrzej

2016-08-05

The aim of our study was to assess the aerobic biodegradation of four selected sulfonamides (sulfanilamide, sulfamethoxazole, sulfadiazine and sulfathiazole) using water samples drawn from highly polluted rivers. Additionally, we aimed to identify the factors that have a significant effect on the process efficiency. The 19 water samples were collected from Brynica and Czarna Przemsza rivers (in Poland) at the same location at approximately monthly intervals. A characteristic feature of the results is the presence of significant differences between the rates of sulfonamides biodegradation in particular samples. The sulfonamide most resistant to biodegradation was sulfamethoxazole, whereas sulfathiazole was most biodegradable. Seasonal variations and related microbial population changes had the most significant effects on sulfonamides biodegradation, e.g., the studied process was highly inhibited during wintertime. A decrease in the biodegradation rate in the river water could be caused by an accidental water pollution by industrial wastewater with heavy metals, an increase in salinity and a decrease in pH, and turbidity. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel meloxicam releasing electrospun polymer/ceramic reinforced biodegradable membranes for periodontal regeneration applications

Energy Technology Data Exchange (ETDEWEB)

Yar, Muhammad, E-mail: drmyar@ciitlahore.edu.pk [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Farooq, Ariba [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Shahzadi, Lubna; Khan, Abdul Samad [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Mahmood, Nasir [Department of Allied Health Sciences and Chemical Pathology, Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore (Pakistan); Rauf, Abdul [Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Chaudhry, Aqif Anwar [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Rehman, Ihtesham ur [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Department of Materials Science and Engineering, The Kroto Research Institute, The University of Sheffield, North Campus, Broad Lane, Sheffield S3 7HQ (United Kingdom)

2016-07-01

Periodontal disease is associated with the destruction of periodontal tissues, along with other disorders/problems including inflammation of tissues and severe pain. This paper reports the synthesis of meloxicam (MX) immobilized biodegradable chitosan (CS)/poly(vinyl alcohol) (PVA)/hydroxyapatite (HA) based electrospun (e-spun) fibers and films. Electrospinning was employed to produce drug loaded fibrous mats, whereas films were generated by solvent casting method. In-vitro drug release from materials containing varying concentrations of MX revealed that the scaffolds containing higher amount of drug showed comparatively faster release. During initial first few hours fast release was noted from membranes and films; however after around 5 h sustained release was achieved. The hydrogels showed good swelling property, which is highly desired for soft tissue engineered implants. To investigate the biocompatibility of our synthesized materials, VERO cells (epithelial cells) were selected and cell culture results showed that these all materials were non-cytotoxic and also these cells were very well proliferated on these synthesized scaffolds. These properties along with the anti-inflammatory potential of our fabricated materials suggest their effective utilization in periodontital treatments. - Highlights: • NSAIDs releasing scaffolds for periodontal regeneration applications • Meloxicam immobilized biodegradable nanocomposite electrospun membranes and films • Good swelling properties • Controlled drug release • VERO cells were very well proliferated and synthesized materials were found to be non-cytotoxic.

Novel meloxicam releasing electrospun polymer/ceramic reinforced biodegradable membranes for periodontal regeneration applications

International Nuclear Information System (INIS)

Yar, Muhammad; Farooq, Ariba; Shahzadi, Lubna; Khan, Abdul Samad; Mahmood, Nasir; Rauf, Abdul; Chaudhry, Aqif Anwar; Rehman, Ihtesham ur

2016-01-01

Periodontal disease is associated with the destruction of periodontal tissues, along with other disorders/problems including inflammation of tissues and severe pain. This paper reports the synthesis of meloxicam (MX) immobilized biodegradable chitosan (CS)/poly(vinyl alcohol) (PVA)/hydroxyapatite (HA) based electrospun (e-spun) fibers and films. Electrospinning was employed to produce drug loaded fibrous mats, whereas films were generated by solvent casting method. In-vitro drug release from materials containing varying concentrations of MX revealed that the scaffolds containing higher amount of drug showed comparatively faster release. During initial first few hours fast release was noted from membranes and films; however after around 5 h sustained release was achieved. The hydrogels showed good swelling property, which is highly desired for soft tissue engineered implants. To investigate the biocompatibility of our synthesized materials, VERO cells (epithelial cells) were selected and cell culture results showed that these all materials were non-cytotoxic and also these cells were very well proliferated on these synthesized scaffolds. These properties along with the anti-inflammatory potential of our fabricated materials suggest their effective utilization in periodontital treatments. - Highlights: • NSAIDs releasing scaffolds for periodontal regeneration applications • Meloxicam immobilized biodegradable nanocomposite electrospun membranes and films • Good swelling properties • Controlled drug release • VERO cells were very well proliferated and synthesized materials were found to be non-cytotoxic.

Species dependent studies of no-carrier-added 93mMo: A green method

International Nuclear Information System (INIS)

Mandal, Swadesh; Nayak, Dalia

2010-01-01

The present paper reports a combination of radioanalytical and green methodology for the ultra-trace scale speciation of molybdenum. The differential attitude of iron-doped calcium alginate (Fe-CA) and chitosan biopolymers towards no-carrier-added 93m Mo radionuclide was studied to develop environmentally sustainable speciation methodology in ultra-trace scale. The affinity of 93m Mo towards the Fe-CA beads is greater than that of chitosan. Species information was obtained by comparing the adsorption profile of 93m Mo on Fe-CA and chitosan biopolymer with the software code CHEAQS PRO program. From the experimental results it is concluded that no-carrier-added 93m Mo radionuclide form mononuclear species instead of polynuclear species in aqueous solution. Use of biodegradable, non-toxic biopolymer makes this method a step forward towards green chemistry.

Soluble polymer conjugates for drug delivery.

Science.gov (United States)

Minko, Tamara

2005-01-01

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

Biodegradable Sonobuoy Decelerators

Science.gov (United States)

2015-06-01

of Water Temperature and the Presence of Salt on the Disintegration Time of MonoSol A200 PVOH...polyhydroxyalkanoate (PHA). The proposed film would disintegrate , dissolve, and eventually biodegrade to prevent long-term effects on marine life. Ensuring no...Standard Specification for Non-Floating Biodegradable Plastics in the Marine Environment. Results showed that no PHA grades were toxic to the marine

Development, optimization and evaluation of curcumin loaded biodegradable crosslinked gelatin film for the effective treatment of periodontitis.

Science.gov (United States)

Chauhan, Sheetal; Bansal, Monika; Khan, Gayasuddin; Yadav, Sarita K; Singh, Ashish K; Prakash, Pradyot; Mishra, Brahmeshwar

2018-07-01

Aim of the present study was to prepare curcumin (CUR) loaded biodegradable crosslinked gelatin (GE) film to alleviate the existing shortcomings in the treatment of periodontitis. Gelatin film was optimized to provide anticipated mucoadhesive strength, mechanical properties, folding endurance, and prolonged drug release over treatment duration, for successful application in the periodontitis. The film was developed by using solvent casting technique and "Design of Experiments" approach was employed for evaluating the influence of independent variables on dependent response variables. Solid-state characterization of the film was performed by FTIR, XRD, and SEM. Further, prepared formulations were evaluated for drug content uniformity, surface pH, folding endurance, swelling index, mechanical strength, mucoadhesive strength, in vitro biodegradation, and in vitro drug release behavior. Solid state characterization of the formulation showed that CUR is physico-chemically compatible with other excipients and CUR was entrapped in an amorphous form inside the smooth and uniform film. The optimized film showed degree of crosslinking 51.04 ± 2.4, swelling index 138.10 ± 1.25, and folding endurance 270 ± 3 with surface pH around 7.0. Crosslinker concentrations positively affected swelling index and biodegradation of film due to altered matrix density of the polymer. Results of in vitro drug release demonstrated the capability of the developed film for efficiently delivering CUR in a sustained manner up to 7 days. The developed optimized film could be considered as a promising delivery strategy to administer medicament locally into the periodontal pockets for the safe and efficient management of periodontitis.

Biodegradation of different petroleum hydrocarbons by free and immobilized microbial consortia.

Science.gov (United States)

Shen, Tiantian; Pi, Yongrui; Bao, Mutai; Xu, Nana; Li, Yiming; Lu, Jinren

2015-12-01

The efficiencies of free and immobilized microbial consortia in the degradation of different types of petroleum hydrocarbons were investigated. In this study, the biodegradation rates of naphthalene, phenanthrene, pyrene and crude oil reached about 80%, 30%, 56% and 48% under the optimum environmental conditions of free microbial consortia after 7 d. We evaluated five unique co-metabolic substances with petroleum hydrocarbons, α-lactose was the best co-metabolic substance among glucose, α-lactose, soluble starch, yeast powder and urea. The orthogonal biodegradation analysis results showed that semi-coke was the best immobilized carrier followed by walnut shell and activated carbon. Meanwhile, the significance of various factors that contribute to the biodegradation of semi-coke immobilized microbial consortia followed the order of: α-lactose > semi-coke > sodium alginate > CaCl2. Moreover, the degradation rate of the immobilized microbial consortium (47%) was higher than that of a free microbial consortium (26%) under environmental conditions such as the crude oil concentration of 3 g L(-1), NaCl concentration of 20 g L(-1), pH at 7.2-7.4 and temperature of 25 °C after 5 d. SEM and FTIR analyses revealed that the structure of semi-coke became more porous and easily adhered to the microbial consortium; the functional groups (e.g., hydroxy and phosphate) were identified in the microbial consortium and were changed by immobilization. This study demonstrated that the ability of microbial adaptation to the environment can be improved by immobilization which expands the application fields of microbial remediation.

Fabrication of biodegradable PEG-PLA nanospheres for solubility, stabilization, and delivery of curcumin.

Science.gov (United States)

Liang, Hongying; Friedman, Joel M; Nacharaju, Parimala

2017-03-01

Curcumin is an effective and safe anticancer agent, and also known to induce vasodilation, but its hydrophobicity limits its clinical application. In this study, a simple emulsion method was developed to prepare biodegradable poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) nanospheres to encapsulate curcumin to improve its solubility and stability. The nanoparticle size was around 150 nm with a narrow size distribution. Fluorescence microscopy showed that curcumin encapsulated PEG-PLA nanospheres were taken up rapidly by Hela and MDA-MB-231 cancer cells. This novel nanoparticulate carrier may improve the bioavailability of curcumin without affecting its anticancer properties.

Histological evaluation of different biodegradable and non-biodegradable membranes implanted subcutaneously in rats

DEFF Research Database (Denmark)

Zhao, S; Pinholt, E M; Madsen, J E

2000-01-01

Different types of biodegradable membranes have become available for guided tissue regeneration. The purpose of this study was to evaluate histologically three different biodegradable membranes (Bio-Gide, Resolut and Vicryl) and one non-biodegradable membrane (expanded polytetrafluoroethylene/e-PTFE...... that e-PTFE was well tolerated and encapsulated by a fibrous connective tissue capsule. There was capsule formation around Resolut and Vicryl and around Bio-Gide in the early phase there was a wide inflammatory zone already. e-PTFE and Vicryl were stable materials while Resolut and Bio-Gide fragmented...