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Showing papers on "Drug carrier published in 2008"


Journal ArticleDOI
15 Apr 2008-Polymer
TL;DR: Recent progress in overcoming challenges with regards to effectively delivering hydrogels inside the body without implantation, prolonging the release kinetics of drugs fromhydrogels, and expanding the nature of drugs which can be delivered using hydrogel-based approaches is discussed.

3,140 citations


Journal ArticleDOI
TL;DR: An overview on some of the currently used systems for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles is provided.
Abstract: The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed.

3,140 citations


Journal ArticleDOI
TL;DR: Gold nanoparticles provide non-toxic carriers for drug and gene delivery applications and their interaction with thiols is an effective and selective means of controlled intracellular release.

2,383 citations


Journal ArticleDOI
TL;DR: This review gives an account of the different drug delivery systems which make use of albumin as a drug carrier with a focus on those systems that have reached an advanced stage of preclinical evaluation or that have entered clinical trials.

1,913 citations


Journal ArticleDOI
TL;DR: Hydrogel nanoparticles have gained considerable attention in recent years as one of the most promising nanoparticulate drug delivery systems owing to their unique potentials via combining the characteristics of a hydrogel system with a nanoparticle, each with its own advantages and drawbacks.

1,704 citations


Journal ArticleDOI
Zonghua Liu1, Yanpeng Jiao1, Wang Yifei1, Changren Zhou1, Ziyong Zhang1 
TL;DR: In this review, four mechanisms are introduced to prepare polysaccharides-based nanoparticles, that is, covalent crosslinking, ionic crossl linking, polyelectrolyte complex, and the self-assembly of hydrophobically modified poly Saccharides.

1,508 citations


Journal ArticleDOI
TL;DR: This review describes the recent developments of microgel/nanogel particles as drug delivery carriers for biological and biomedical applications, including stability for prolonged circulation in the blood stream, novel functionality for further bioconjugation, and biodegradability for sustained release of drugs for a desired period of time.

1,444 citations


Journal ArticleDOI
TL;DR: A review of the state-of-the-art in responsive polymer systems for controlled drug delivery applications is given in this article, where the authors describe different types of stimuli-sensitive systems and give an account of their synthesis through methods such as group transfer polymerization, atom transfer radical polymerization and reversible addition-fragmentation chain transfer polymerisation.

1,186 citations


Journal ArticleDOI
TL;DR: These studies suggest that Pluronics have a broad spectrum of biological response modifying activities which make it one of the most potent drug targeting systems available, resulting in a remarkable impact on the emergent field of nanomedicine.

1,111 citations


Journal ArticleDOI
TL;DR: Important findings of the past decade on the encapsulation and release profiles of macromolecular therapeutics from PLGA and PLGA-based nano/microparticles are discussed critically in relation to nature and type of bioactive molecule, carrier polymer and experimental variables that influence the delivery of macrochemical therapeutics.

999 citations


Journal ArticleDOI
TL;DR: Accumulation of iron oxide nanoparticles in gliosarcomas can be significantly enhanced by magnetic targeting and successfully quantified by MR imaging, and these nanoparticles appear to be a promising vehicle for glioma-targeted drug delivery.

Journal ArticleDOI
TL;DR: This review focuses on recent development of the preparation and application for drug delivery of the block copolymer hydrogels that respond to temperature, pH or both stimuli, including poly(N-substituted acrylamide)-based blockcopolymers, poloxamers and their derivatives, poly(ethylene glycol)-polyester block copolemers, polyelectrolyte-based blockCopolymers and the polyelectrodynamic-modified thermo-sensitive block

Journal ArticleDOI
TL;DR: This work used rapid and tunable mixing through hydrodynamic flow focusing in microfluidic channels to control nanoprecipitation of poly(lactic- co-glycolic acid)- b-poly(ethylene glycol) diblock copolymers as a model polymeric biomaterial for drug delivery.
Abstract: A central challenge in the development of drug-encapsulated polymeric nanoparticles is the inability to control the mixing processes required for their synthesis resulting in variable nanoparticle physicochemical properties. Nanoparticles may be developed by mixing and nanoprecipitation of polymers and drugs dissolved in organic solvents with nonsolvents. We used rapid and tunable mixing through hydrodynamic flow focusing in microfluidic channels to control nanoprecipitation of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) diblock copolymers as a model polymeric biomaterial for drug delivery. We demonstrate that by varying (1) flow rates, (2) polymer composition, and (3) polymer concentration we can optimize the size, improve polydispersity, and control drug loading and release of the resulting nanoparticles. This work suggests that microfluidics may find applications for the development and optimization of polymeric nanoparticles in the newly emerging field of nanomedicine.

Journal ArticleDOI
TL;DR: New cationic polyrotaxanes composed of multiple oligoethylenimine-grafted CDs threaded and end-capped on a block copolymer chain were designed and synthesized as a new class of polymeric gene delivery vectors, where the chain-interlocked cationIC cyclic units formed an integrated supramolecular entity to function as a macromolecular gene vector.

Journal ArticleDOI
TL;DR: This review presents an overview of the literature regarding different shedding strategies that have been investigated for the preparation of sterically stabilized nanoparticulate by means of shedding, i.e. a loss of the coating after arrival at the target site.
Abstract: Nanoparticles, such as liposomes, polymeric micelles, lipoplexes and polyplexes are frequently studied as targeted drug carrier systems. The ability of these particles to circulate in the bloodstream for a prolonged period of time is often a prerequisite for successful targeted delivery. To achieve this, hydrophilic ‘stealth’ polymers, such as poly(ethylene glycol) (PEG), are used as coating materials. Such polymers shield the particle surface and thereby reduce opsonization by blood proteins and uptake by macrophages of the mononuclear phagocyte system. Yet, after localizing in the pathological site, nanoparticles should deliver their contents in an efficient manner to achieve a sufficient therapeutic response. The polymer coating, however, may hinder drug release and target cell interaction and can therefore be an obstacle in the realization of the therapeutic response. Attempts have been made to enhance the therapeutic efficacy of sterically stabilized nanoparticles by means of shedding, i.e. a loss of the coating after arrival at the target site. Such an ‘unmasking’ process may facilitate drug release and/or target cell interaction processes. This review presents an overview of the literature regarding different shedding strategies that have been investigated for the preparation of sterically stabilized nanoparticulates. Detach mechanisms and stimuli that have been used are described.

Journal ArticleDOI
TL;DR: Drug nanoparticles have been shown to improve bioavailability and enhance drug exposure for oral and parenteral dosage forms and can be identified with milligram quantities of drug substance, providing the discovery scientist with an alternate avenue for screening and identifying superior analogs.
Abstract: More than 40% of compounds identified through combinatorial screening programs are poorly soluble in water. These molecules are difficult to formulate using conventional approaches and are associated with innumerable formulation-related performance issues. Formulating these compounds as pure drug nanoparticles is one of the newer drug-delivery strategies applied to this class of molecules. Nanoparticle dispersions are stable and have a mean diameter of less than 1 micron. The formulations consist of water, drug, and one or more generally regarded as safe excipients. These liquid dispersions exhibit an acceptable shelf-life and can be postprocessed into various types of solid dosage forms. Drug nanoparticles have been shown to improve bioavailability and enhance drug exposure for oral and parenteral dosage forms. Suitable formulations for the most commonly used routes of administration can be identified with milligram quantities of drug substance, providing the discovery scientist with an alternate avenue for screening and identifying superior analogs. For the toxicologist, the approach provides a means for dose escalation using a formulation that is commercially viable. In the past few years, formulating poorly water-soluble compounds using a nanoparticulate approach has evolved from a conception to a realization whose versatility and applicability are just beginning to be realized.

Journal ArticleDOI
TL;DR: Fluorescence quenching showed that curcumin molecules quench the intrinsic fluorescence of caseins upon binding, and the utility of CMs as carriers ofCurcumin was evaluated by using in vitro cultured HeLa cells.

Journal ArticleDOI
TL;DR: It has unambiguously been proven that this tumor-targeting DDS works exactly as designed and shows high potency toward specific cancer cell lines, thereby forming a solid foundation for further development.
Abstract: A novel single-walled carbon nanotube (SWNT)-based tumor-targeted drug delivery system (DDS) has been developed, which consists of a functionalized SWNT linked to tumor-targeting modules as well as prodrug modules. There are three key features of this nanoscale DDS: (a) use of functionalized SWNTs as a biocompatible platform for the delivery of therapeutic drugs or diagnostics, (b) conjugation of prodrug modules of an anticancer agent (taxoid with a cleavable linker) that is activated to its cytotoxic form inside the tumor cells upon internalization and in situ drug release, and (c) attachment of tumor-recognition modules (biotin and a spacer) to the nanotube surface. To prove the efficacy of this DDS, three fluorescent and fluorogenic molecular probes were designed, synthesized, characterized, and subjected to the analysis of the receptor-mediated endocytosis and drug release inside the cancer cells (L1210FR leukemia cell line) by means of confocal fluorescence microscopy. The specificity and cytotoxicity of the conjugate have also been assessed and compared with L1210 and human noncancerous cell lines. Then, it has unambiguously been proven that this tumor-targeting DDS works exactly as designed and shows high potency toward specific cancer cell lines, thereby forming a solid foundation for further development.

Journal ArticleDOI
TL;DR: The drugs in combination incorporated in MNPs demonstrated highly synergistic antiproliferative activity in MCF-7 breast cancer cells, and MNPs with combined characteristics of MRI and drug delivery could be of high clinical significance in the treatment of various disease conditions.

Journal ArticleDOI
TL;DR: The results showed that the entrapment of 8-MOP in nanoparticulate systems could minimize the permeation differentiation between normal and hyperproliferative skin compared to the free drug in an aqueous control.

Journal ArticleDOI
TL;DR: The fabrication and chemical modifications of porous silicon for biomedical applications, and also the potential advantages of PSi in drug delivery are reviewed.

Journal ArticleDOI
TL;DR: New technologies that combine the use of nanoparticles with acoustic power both in drug and gene delivery both in vitro and in vivo are summarized.

Journal ArticleDOI
TL;DR: The potential of dendrimers to be applied in these detailed routes with particular reference to intravenous, oral, transdermal, and ocular delivery systems is demonstrated.

Journal ArticleDOI
TL;DR: The delivery of CPT to tumor tissues at a high concentration, with the assistance of HGC nanoparticles, exerted a potent therapeutic effect and reveal the promising potential of H GC nanoparticles-encapsulated CPT as a stable and effective drug delivery system in cancer therapy.

Journal ArticleDOI
TL;DR: How the complex interplay among cancer biology, the CD44-HA interaction, drug carriers and drug targeting has been used to improve anticancer therapies is described to hold the prospect of significantly improved targeted anticancer treatments.
Abstract: The complex system involved in the synthesis, degradation and binding of the high molecular weight glycosaminoglycan hyaluronic acid (hyaluronan or HA) provides a variety of structures that can be exploited for targeted cancer therapy. In many cancers of epithelial origin there is an upregulation of CD44, a receptor that binds HA. In other cancers, HA in the tumor matrix is overexpressed. Both CD44 on cancer cells and HA in the matrix have been targets for anticancer therapy. Even though CD44 is expressed in normal epithelial cells and HA is part of the matrix of normal tissues, selective targeting to cancer is possible. This is because macromolecular carriers predominantly extravasate into the tumor and not normal tissue; thus CD44-HA targeted carriers administered intravenously localize preferentially into tumors. Anti-CD44 antibodies have been used in patients to deliver radioisotopes or mertansine for treatment of CD44 expressing tumors. In early phase clinical trials, patients with breast or head and neck tumors treated with anti-CD44 conjugates experienced stabilized disease. A dose-limiting toxicity was associated with distribution of the antibody-drug conjugate to the skin, a site in the body with a high level of CD44. HA has been used as a drug carrier and a ligand on liposomes or nanoparticles to target drugs to CD44 overexpressing cells. Drugs can be attached to HA via the carboxylate on the glucuronic acid residue, the hydroxyl on the N-acetylglucosamine or the reducing end which are located on a repeating disaccharide. Drugs delivered in HA-modified liposomes exhibited excellent antitumor activity both in vitro and in murine tumor models. The HA matrix is also a potential target for anticancer therapies. By manipulating the interaction of HA with cell surface receptors, either by degrading it with hyaluronidase or by interfering with CD44-HA interactions using soluble CD44 proteins, tumor progression was blocked. Finally, cytotoxic drugs or prodrug converting enzymes can be attached to the HA matrix to generate a cytotoxic fence around the tumor. This review describes how the complex interplay among cancer biology, the CD44-HA interaction, drug carriers and drug targeting has been used to improve anticancer therapies. As these approaches evolve, they hold forth the prospect of significantly improved targeted anticancer treatments.

Journal ArticleDOI
TL;DR: Results from early clinical trials of these polymer-drug conjugates have demonstrated several advantages over the corresponding parent drugs, including fewer side effects, enhanced therapeutic efficacy, ease of drug administration, and improved patient compliance, which warrant further clinical development of polymer- drug conjugate as a new class of anticancer agents.

Journal ArticleDOI
TL;DR: The mechanisms by which drug molecules access the lymph and the formulation strategies that may be utilised to enhance lymphatic drug transport are described, directed toward recent advances in understanding regarding the impact of lipid source and intracellular lipid trafficking pathways.

Journal ArticleDOI
TL;DR: Applications and comparative benefits of use of cyclodextrins (CDs) and their derivatives in the design of novel delivery systems like liposomes, microspheres, microcapsules, nanoparticles,cyclodextrin grafted cellulosic fabric, hydrogels, nanosponges, beads, nanogels/nanoassemblies and cyclodeXTrin-containing polymers are outlined.
Abstract: The versatile pharmaceutical material cyclodextrin’s (CDs) are classified into hydrophilic, hydrophobic, and ionic derivatives. By the early 1950s the basic physicochemical characteristics of cyclodextrins had been discovered, since than their use is a practical and economical way to improve the physicochemical and pharmaceutical properties such as solubility, stability, and bioavailability of administered drug molecules. These CDs can serve as multi-functional drug carriers, through the formation of inclusion complex or the form of CD/drug conjugate and, thereby potentially serving as novel drug carriers. This contribution outlines applications and comparative benefits of use of cyclodextrins (CDs) and their derivatives in the design of novel delivery systems like liposomes, microspheres, microcapsules, nanoparticles, cyclodextrin grafted cellulosic fabric, hydrogels, nanosponges, beads, nanogels/nanoassemblies and cyclodextrin-containing polymers. The article also focuses on the ability of CDs to enhance the drug absorption across biological barriers, the ability to control the rate and time profiles of drug release, drug safety, drug stability, and the ability to deliver a drug to targeted site. The article highlight’s on needs, limitations and advantages of CD based delivery systems. CDs, because of their continuing ability to find several novel applications in drug delivery, are expected to solve many problems associated with the delivery of different novel drugs through different delivery routes.

Journal ArticleDOI
TL;DR: The results reveal that the multifunctional hydroxyapatites exhibit the typical ordered characteristics of the hexagonal mesostructure, and have rod-like morphology with the particle size of 20-40 nm in width and 100-200 nm in length.

Journal ArticleDOI
TL;DR: The most important advantages of this type of "living" drug release strategy are highlighted, but also its limitations pointed out, and the major challenges to be addressed in the forthcoming years are described.