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Showing papers on "Drug carrier published in 2003"


Journal ArticleDOI
TL;DR: Based on the above mechanism, various potential applications of nanoparticles for delivery of therapeutic agents to the cells and tissue are discussed.

3,269 citations


Journal ArticleDOI
TL;DR: An MCM-41 type mesoporous silica nanosphere-based controlled-release delivery system has been synthesized and characterized using surface-derivatized cadmium sulfide nanocrystals as chemically removable caps to encapsulate several pharmaceutical drug molecules and neurotransmitters inside the organically functionalized MSN Mesoporous framework.
Abstract: An MCM-41 type mesoporous silica nanosphere-based (MSN) controlled-release delivery system has been synthesized and characterized using surface-derivatized cadmium sulfide (CdS) nanocrystals as chemically removable caps to encapsulate several pharmaceutical drug molecules and neurotransmitters inside the organically functionalized MSN mesoporous framework. We studied the stimuli-responsive release profiles of vancomycin- and adenosine triphosphate (ATP)-loaded MSN delivery systems by using disulfide bond-reducing molecules, such as dithiothreitol (DTT) and mercaptoethanol (ME), as release triggers. The biocompatibility and delivery efficiency of the MSN system with neuroglial cells (astrocytes) in vitro were demonstrated. In contrast to many current delivery systems, the molecules of interest were encapsulated inside the porous framework of the MSN not by adsorption or sol−gel types of entrapment but by capping the openings of the mesoporous channels with size-defined CdS nanoparticles to physically block...

1,597 citations


Journal ArticleDOI
TL;DR: The potential utility of multimolecular assembly derived from heterobifunctional PEGs and block copolymers were explored to systematically modify the properties of metal and semiconductor nanostructures by controlling their structure and their surface properties, making them extremely attractive for use in biological and biomedical applications.

1,469 citations


Journal ArticleDOI
TL;DR: NanoCrystal Technology is an attrition process wherein large micron size drug crystals are media milled in a water-based stabilizer solution and the process generates physically stable dispersions consisting of nanometer-sized drug crystals.

1,245 citations


Journal ArticleDOI
TL;DR: The purpose of this minireview is to provide a concise, yet detailed, introduction to the use of ABCs and polymeric micelles as delivery agents as well as to highlight current and past work in this area.

1,014 citations


Journal ArticleDOI
TL;DR: An update of drug delivery using poly(ethylene glycol) (PEG), that focuses on recent developments in both protein and organic drugs, is presented, that includes applications of high molecular weight PEG prodrug strategies to amino containing drugs.

939 citations


Journal ArticleDOI
TL;DR: The potential of using ceramic-based nanoparticles as drug carriers for photodynamic therapy has been demonstrated and the active uptake of drug-doped nanoparticles into the cytosol of tumor cells is demonstrated.
Abstract: A novel nanoparticle-based drug carrier for photodynamic therapy is reported which can provide stable aqueous dispersion of hydrophobic photosensitizers, yet preserve the key step of photogeneration of singlet oxygen, necessary for photodynamic action. A multidisciplinary approach is utilized which involves (i) nanochemistry in micellar cavity to produce these carriers, (ii) spectroscopy to confirm singlet oxygen production, and (iii) in vitro studies using tumor cells to investigate drug-carrier uptake and destruction of cancer cells by photodynamic action. Ultrafine organically modified silica-based nanoparticles (diameter approximately 30 nm), entrapping water-insoluble photosensitizing anticancer drug 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide, have been synthesized in the nonpolar core of micelles by hydrolysis of triethoxyvinylsilane. The resulting drug-doped nanoparticles are spherical, highly monodispersed, and stable in aqueous system. The entrapped drug is more fluorescent in aqueous medium than the free drug, permitting use of fluorescence bioimaging studies. Irradiation of the photosensitizing drug entrapped in nanoparticles with light of suitable wavelength results in efficient generation of singlet oxygen, which is made possible by the inherent porosity of the nanoparticles. In vitro studies have demonstrated the active uptake of drug-doped nanoparticles into the cytosol of tumor cells. Significant damage to such impregnated tumor cells was observed upon irradiation with light of wavelength 650 nm. Thus, the potential of using ceramic-based nanoparticles as drug carriers for photodynamic therapy has been demonstrated.

902 citations


Journal ArticleDOI
TL;DR: This review presents the outstanding contributions in field of biodegradable microspheres as protein delivery systems, their methods of preparation, drug release, stability, interaction with immune system and regulatory considerations.

826 citations


Journal ArticleDOI
TL;DR: It was shown that the drugs were capsulated inside of the fibers and the drug release in the presence of proteinase K followed nearly zero-order kinetics due to the degradation of the PLLA fibers.

824 citations


Journal ArticleDOI
TL;DR: Chitosan appears to be a promising material for GI drug and gene delivery applications as many derivatives and formulations are being examined.

821 citations


Journal ArticleDOI
TL;DR: This work represents the first successful demonstration of plasmid DNA incorporation into a polymer scaffold using electrospinning, and when tested under tensile loads, the electrospun polymer/DNA composite scaffolds exhibited tensile moduli values that approximate those of skin and cartilage.

Journal ArticleDOI
TL;DR: Vitamin E TPGS has great advantages for the manufacture of polymeric nanoparticles for controlled release of paclitaxel and other anti-cancer drugs and could be a novel surfactant as a matrix material when blended with other biodegradable polymers.

Journal ArticleDOI
Yongmei Xu1, Yumin Du1
TL;DR: The encapsulation efficiency was highly decreased by increase of initial BSA and chitosan concentration; higher loading capacity of BSA speeded the BSA release from the nanoparticles.

Journal Article
TL;DR: Improved drug delivery systems are required for drugs currently in use to treat localized diseases of the colon and the concept of using pH as a rigger to release a drug in the colon is based on the pH conditions that vary continuously down the gastrointestinal tract.
Abstract: Purpose. Although oral delivery has become a widely accepted route of administration of therapeutic drugs, the gastrointestinal tract presents several formidable barriers to drug delivery. Colonic drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon but also for its potential for the delivery of proteins and therapeutic peptides. To achieve successful colonic delivery, a drug needs to be protected from absorption and /or the environment of the upper gastrointestinal tract (GIT) and then be abruptly released into the proximal colon, which is considered the optimum site for colon-tar- geted delivery of drugs. Colon targeting is naturally of value for the topical treatment of diseases of colon such as Chron's diseases, ulcerative colitis, colorectal cancer and amebiasis. Peptides, proteins, oligonucleotides and vac- cines pose potential candidature for colon targeted drug delivery. Methods. The various strategies for targeting orally administered drugs to the colon include covalent linkage of a drug with a carrier, coating with pH-sensitive polymers, formulation of timed released systems, exploita- tion of carriers that are degraded specifically by colonic bacteria, bioadhesive systems and osmotic controlled drug delivery systems. Various prodrugs (sulfasalazine, ipsala- zine, balsalazine and olsalazine) have been developed that are aimed to deliver 5-amino salicylic acid (5-ASA) for localized chemotherapy of inflammatory bowl disease (IBD). Microbially degradable polymers especially azo crosslinked polymers have been investigated for use in tar- geting of drugs to colon. Certain plant polysaccharides such as amylose, inulin, pectin and guar gum remains unaf- fected in the presence of gastrointestinal enzymes and pave the way for the formulation of colon targeted drug delivery systems. The concept of using pH as a rigger to release a drug in the colon is based on the pH conditions that vary continuously down the gastrointestinal tract. Times dependent drug delivery systems have been devel- oped that are based on the principle to prevent release of drug until 3-4 h after leaving the stomach. Redox sensitive polymers and bioadhesive systems have also been exploited to deliver the drugs into the colon. Results. The approach that is based on the formation of prodrug involves covalent linkage between drug and carrier. The type of linkage that is formed between drug and carrier would decide the triggering mechanism for the release of drug in colon. The presence of azo reductase enzymes play pivotal role in the release of drug from azo bond prodrugs while glycosidase activity of the colonic microflora is responsible for liberation of drugs from glycosidic pro- drugs. Release of drugs from azo polymer coated dosage forms is supposed to take place after reduction and thus cleavage of the azo bonds by the azoreductase enzymes present in the colonic microflora. Natural polysaccharides have been used as tools to deliver the drugs specifically to the colon. These polysaccharides remain intact in the phys- iological environment of stomach and small intestine but once the dosage form enters into colon, it is acted upon by polysaccharidases, which degrades the polysaccharide and releases the drug into the vicinity of bioenvironment of colon. However, they should be protected while gaining entry into stomach and small intestine due to enormous swelling and hydrophilic properties of polysaccharides. This has been achieved either by chemical crosslinking or by addition of a protective coat. Formulation coated with enteric polymers releases drug when pH move towards alkaline range while as the multicoated formulation passes the stomach, the drug is released after a lag time of 3-5 h that is equivalent to small intestinal transit time. Drug coated with a bioadhesive polymer that selectively provides adhesion to the colonic mucosa may release drug in the colon. Conclusions. Improved drug delivery systems are required for drugs currently in use to treat localized dis- eases of the colon. The advantages of targeting drugs spe- cifically to the diseased colon are reduced incidence of systemic side effects, lower dose of drug, supply of the drug to the biophase only when it is required and mainte- nance of the drug in its intact form as close as possible to the target site.

Journal ArticleDOI
TL;DR: In vitro results demonstrated that the mixed micelles were more effective in tumor cell kill due to accelerated drug release and folate receptor-mediated tumor uptake and after internalization polyHis was found to be effective for cytosolic ADR delivery by virtue of fusogenic activity.

Journal ArticleDOI
TL;DR: Intravenous administration of tumor-specific 2C5 immunomicelles loaded with a sparingly soluble anticancer agent, taxol, into experimental mice bearing Lewis lung carcinoma resulted in an increased accumulation of taxol in the tumor compared with free taxol orTaxol in nontargeted micelles and in enhanced tumor growth inhibition.
Abstract: To prepare immunomicelles, new targeted carriers for poorly soluble pharmaceuticals, a procedure has been developed to chemically attach mAbs to reactive groups incorporated into the corona of polymeric micelles made of polyethylene glycol–phosphatidylethanolamine conjugates. Micelle-attached antibodies retained their ability to specifically interact with their antigens. Immunomicelles with attached antitumor mAb 2C5 effectively recognized and bound various cancer cells in vitro and showed an increased accumulation in experimental tumors in mice when compared with nontargeted micelles. Intravenous administration of tumor-specific 2C5 immunomicelles loaded with a sparingly soluble anticancer agent, taxol, into experimental mice bearing Lewis lung carcinoma resulted in an increased accumulation of taxol in the tumor compared with free taxol or taxol in nontargeted micelles and in enhanced tumor growth inhibition. This family of pharmaceutical carriers can be used for the solubilization and enhanced delivery of poorly soluble drugs to various pathological sites in the body.

Journal ArticleDOI
TL;DR: Advantages, limitations, and possible future developments in pectin-based formulations with particular emphasis on the field of colon-specific drug delivery are discussed.

Journal ArticleDOI
TL;DR: The spectrum of potential applications of bioadhesive microspheres in controlled drug delivery ranging from the small molecules, to peptides, and to the macromolecular drugs such as proteins, oligonucleotides and even DNA is presented.

Journal ArticleDOI
TL;DR: The stealthiness introduced to liposomes through PEGylation is extended here with completely synthetic polymersomes, which are vesicles composed entirely of PEG-based block copolymer amphiphiles that are not only more proportionately designed, but also have already been shown to considerably broaden the range of vesicle properties.

Journal ArticleDOI
TL;DR: PEGylation has been found to be suitable for modification of PAMAM dendrimers for reduction of drug leakage and hemolytic toxicity and could improve drug-loading capacity and stabilize such systems in body.

Journal ArticleDOI
TL;DR: There is little in vivo or in vitro evidence to suggest that a generalized toxic effect on the BBB is the primary mechanism for drug delivery to the brain, and the fact that dalargin has to be preadsorbed onto nanoparticles before it is effective in inducing antinociception suggests specific mechanisms of Delivery to the CNS.
Abstract: Purpose. It has recently been suggested that the poly(butylcyanoacrylate) (PBCA) nanoparticle drug delivery system has a generalized toxic effect on the blood-brain barrier (BBB) (8) and that this effect forms the basis of an apparent enhanced drug delivery to the brain. The purpose of this study is to explore more fully the mechanism by which PBCA nanoparticles can deliver drugs to the brain.

Journal ArticleDOI
TL;DR: The effectiveness of cancer therapy depends in part on adequate delivery of the therapeutic agents to tumor cells, and a better understanding of the processes and contribution of these factors governing drug delivery may lead to new cancer therapeutic strategies.
Abstract: Purpose The purpose of this review is to provide an overview of the principles of and barriers to drug transport and delivery to solid tumors

Journal ArticleDOI
TL;DR: Collagen gels are flowable, suggesting the possibility of an easily injectable, biocompatible drug delivery matrix, and can act as a "cage" to retain cells or as gene delivery complexes, which are larger than drugs and therapeutic proteins.

Journal ArticleDOI
TL;DR: It was concluded that the ionization of the polyHis block forming the micelle core determined the pH-dependent CMC and stability and pH-sensitive micelles are expected to have application for solid tumor treatment, exploiting the fact that most solid tumors have an acidic extracellular pH.

Journal ArticleDOI
TL;DR: The in vitro release of ib uprofen from drug-dendrimer complex is appreciably slower compared to pure ibuprofen, suggesting that dendrimers may be able to carry the complexed drug inside cells efficiently.

Journal ArticleDOI
TL;DR: In this article, the authors present the state of the art regarding the physico-chemical characterization of these drug carriers, in terms of the particle size distribution, the morphology, the polymer molecular weight, the surface charge, the drug content and the in vitro drug release profiles.
Abstract: Polymeric nanoparticle systems such as nanocapsules and nanospheres present potential applications for the administration of therapeutic molecules. The physico-chemical characteristics of nanoparticle suspensions are important pre-requisites of the success of any dosage form development. The purpose of this review is to present the state of the art regarding the physico-chemical characterization of these drug carriers, in terms of the particle size distribution, the morphology, the polymer molecular weight, the surface charge, the drug content and the in vitro drug release profiles. Part of the review is devoted to the description of the techniques to improve the stability of colloidal systems.

Journal ArticleDOI
TL;DR: Understanding of the mechanisms underlying the biological fate and biodistribution of protein and peptide drugs has advanced to the stage where methods that use or influence these mechanisms are now available, and new approaches to intracellular drug delivery, including the use of transduction proteins and peptides, are being developed.

Journal ArticleDOI
TL;DR: The results indicate that the properties of copolymers could be tailored by adjusting polymer composition, and it is suggested that these matrix polymers may be optimized as carriers in the protein (antigen) delivery system for different purposes.

Journal ArticleDOI
TL;DR: The main clinical and experimental applications covered include: treatment and prophylaxis of bone and soft tissue infections, wound healing, as well as ophthalmic and periodontal treatment.

Journal ArticleDOI
TL;DR: Nebulization of nanoparticles-based ATDs forms a sound basis for improving drug bioavailability and reducing the dosing frequency for better management of pulmonary tuberculosis.
Abstract: Objectives: To improve the bioavailability of antitubercular drugs (ATDs) as well as to assess the feasibility of administering ATDs via the respiratory route, this study reports the formulation of three frontline ATDs, i.e. rifampicin, isoniazid and pyrazinamide encapsulated in poly (DL-lactide-co-glycolide) nanoparticles suit- able for nebulization. Methods: Drug-loaded nanoparticles were prepared by the multiple emulsion technique, vacuum-dried and nebulized to guinea pigs. The formulation was evaluated with respect to the pharmacokinetics of each drug and its chemotherapeutic potential in Mycobacterium tuberculosis infected guinea pigs. Results: The aerosolized particles exhibited a mass median aerodynamic diameter of 1.88 ± 0.11 µm, favour- able for bronchoalveolar lung delivery. A single nebulization to guinea pigs resulted in sustained thera- peutic drug levels in the plasma for 6-8 days and in the lungs for up to 11 days. The elimination half-life and mean residence time of the drugs were significantly prolonged compared to when the parent drugs were administered orally, resulting in an enhanced relative bioavailability (compared to oral administration) for encapsulated drugs (12.7-, 32.8- and 14.7-fold for rifampicin, isoniazid and pyrazinamide, respectively). The absolute bioavailability (compared to intravenous (iv) administration) was also increased by 6.5-, 19.1- and 13.4-fold for rifampicin, isoniazid and pyrazinamide, respectively. On nebulization of nanoparticles contain- ing drugs to M. tuberculosis infected guinea pigs at every 10th day, no tubercle bacilli could be detected in the lung after five doses of treatment whereas 46 daily doses of orally administered drug were required to obtain an equivalent therapeutic benefit.