Showing papers on "Drug carrier published in 2005"
TL;DR: Polyethylene glycol-drug conjugates have several advantages: a prolonged residence in body, a decreased degradation by metabolic enzymes and a reduction or elimination of protein immunogenicity.
2,138 citations
TL;DR: Cyclodextrins, 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.
Abstract: The purpose of this review is to discuss and summarize some of the interesting findings and applications of cyclodextrins (CDs) and their derivatives in different areas of drug delivery, particularly in protein and peptide drug delivery and gene delivery. The article highlights important CD applications in the design of various novel delivery systems like liposomes, microspheres, microcapsules, and nanoparticles. In addition to their well-known effects on drug solubility and dissolution, bioavailability, safety, and stability, their use as excipients in drug formulation are also discussed in this article. The article also focuses on various factors influencing inclusion complex formation because an understanding of the same is necessary for proper handling of these versatile materials. Some important considerations in selecting CDs in drug formulation such as their commercial availability, regulatory status, and patent status are also summarized. 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.
1,135 citations
TL;DR: Targeting methotrexate increased its antitumor activity and markedly decreased its toxicity, allowing therapeutic responses not possible with a free drug, and modified PAMAM dendritic polymers were employed as carriers.
Abstract: Prior studies suggested that nanoparticle drug delivery might improve the therapeutic response to anticancer drugs and allow the simultaneous monitoring of drug uptake by tumors. We employed modified PAMAM dendritic polymers <5 nm in diameter as carriers. Acetylated dendrimers were conjugated to folic acid as a targeting agent and then coupled to either methotrexate or tritium and either fluorescein or 6-carboxytetramethylrhodamine. These conjugates were injected i.v. into immunodeficient mice bearing human KB tumors that overexpress the folic acid receptor. In contrast to nontargeted polymer, folate-conjugated nanoparticles concentrated in the tumor and liver tissue over 4 days after administration. The tumor tissue localization of the folate-targeted polymer could be attenuated by prior i.v. injection of free folic acid. Confocal microscopy confirmed the internalization of the drug conjugates into the tumor cells. Targeting methotrexate increased its antitumor activity and markedly decreased its toxicity, allowing therapeutic responses not possible with a free drug.
916 citations
TL;DR: A novel water-dispersible oleic acid-Pluronic-coated iron oxide magnetic nanoparticle formulation that can be loaded easily with high doses of water-insoluble anticancer agents and demonstrated sustained intracellular drug retention relative to drug in solution and a dose-dependent antiproliferative effect in breast and prostate cancer cell lines.
Abstract: We have developed a novel water-dispersible oleic acid (OA)-Pluronic-coated iron oxide magnetic nanoparticle formulation that can be loaded easily with high doses of water-insoluble anticancer agents Drug partitions into the OA shell surrounding iron oxide nanoparticles, and the Pluronic that anchors at the OA−water interface confers aqueous dispersity to the formulation Neither the formulation components nor the drug loading affected the magnetic properties of the core iron oxide nanoparticles Sustained release of the incorporated drug is observed over 2 weeks under in vitro conditions The nanoparticles further demonstrated sustained intracellular drug retention relative to drug in solution and a dose-dependent antiproliferative effect in breast and prostate cancer cell lines This nanoparticle formulation can be used as a universal drug carrier system for systemic administration of water-insoluble drugs while simultaneously allowing magnetic targeting and/or imaging Keywords: Sustained release; wat
870 citations
TL;DR: In vitro and in vivo studies show that the micelles have the characteristic properties, such as an intracellular pH-triggered drug release capability, tumor-infiltrating permeability, and effective antitumor activity with extremely low toxicity.
703 citations
TL;DR: SBA-15 functionalized by one-pot synthesis is found to be more favorable for the adsorption and release of BSA due to the balance of electrostatic interaction and hydrophilic interaction between BSA and the functionalized SBA- 15 matrix.
Abstract: Mesoporous SBA-15 materials were functionalized with amine groups through postsynthesis and one-pot synthesis, and the resulting functionalized materials were investigated as matrixes for controlled drug delivery. The materials were characterized by FTIR, N2 adsorption/desorption analysis, ζ potential measurement, XRD, XPS, and TEM. Ibuprofen (IBU) and bovine serum albumin (BSA) were selected as model drugs and loaded onto the unmodified and functionalized SBA-15. It was revealed that the adsorption capacities and release behaviors of these model drugs were highly dependent on the different surface properties of SBA-15 materials. The release rate of IBU from SBA-15 functionalized by postsynthesis is found to be effectively controlled as compared to that from pure SBA-15 and SBA-15 functionalized by one-pot synthesis due to the ionic interaction between carboxyl groups in IBU and amine groups on the surface of SBA-15. However, SBA-15 functionalized by one-pot synthesis is found to be more favorable for the...
629 citations
TL;DR: The issues of nanotechnology relevant to the anti-TB drugs are highlighted, which may resolve the problem of nonadherence to prescribed therapy, which is one of the major obstacles in the control of TB epidemics.
Abstract: Nanoparticle-based drug delivery systems have considerable potential for treatment of tuberculosis (TB) The important technological advantages of nanoparticles used as drug carriers are high stability, high carrier capacity, feasibility of incorporation of both hydrophilic and hydrophobic substances, and feasibility of variable routes of administration, including oral application and inhalation Nanoparticles can also be designed to allow controlled (sustained) drug release from the matrix These properties of nanoparticles enable improvement of drug bioavailability and reduction of the dosing frequency, and may resolve the problem of nonadherence to prescribed therapy, which is one of the major obstacles in the control of TB epidemics This article highlights some of the issues of nanotechnology relevant to the anti-TB drugs
628 citations
TL;DR: The results demonstrate that PHSM/f is a viable means for treating drug resistant tumors and may endow the drug carriers to bypass Pgp efflux pump and sequestration of DOX in acidic intracellular compartments, yielding high cytotyoxicity.
556 citations
TL;DR: The intracellular trafficking model proposed was supported through nanoparticle uptake studies which demonstrated that cells expressing the human folate receptor internalized a higher level of nanoparticles than negative control cells.
Abstract: A magnetic nanoparticle conjugate was developed that can potentially serve both as a contrast enhancement agent in magnetic resonance imaging and as a drug carrier in controlled drug delivery, targeted at cancer diagnostics and therapeutics. The conjugate is made of iron oxide nanoparticles covalently bound with methotrexate (MTX), a chemotherapeutic drug that can target many cancer cells whose surfaces are overexpressed by folate receptors. The nanoparticles were first surface-modified with (3-aminopropyl)trimethoxysilane to form a self-assembled monolayer and subsequently conjugated with MTX through amidation between the carboxylic acid end groups on MTX and the amine groups on the particle surface. Drug release experiments demonstrated that MTX was cleaved from the nanoparticles under low pH conditions mimicking the intracellular conditions in the lysosome. Cellular viability studies in human breast cancer cells (MCF-7) and human cervical cancer cells (HeLa) further demonstrated the effectiveness of such chemical cleavage of MTX inside the target cells through the action of intracellular enzymes. The intracellular trafficking model proposed was supported through nanoparticle uptake studies which demonstrated that cells expressing the human folate receptor internalized a higher level of nanoparticles than negative control cells.
555 citations
TL;DR: A new approach to the design of acid-sensitive micelles is developed by incorporating hydrophobic acetal groups on the core block of a micelle-forming block copolymer to change its solubility and disrupting the micelle, triggering drug release.
531 citations
TL;DR: This review will focus on the development of nanoscale drug delivery mechanisms that allow for the delivery of nucleic acids and proteins to specific areas within the body and reduce systemic side effects and allow for more efficient use of the drug.
TL;DR: Recent advances in tumor-targeting drug conjugates including monoclonal antibodies, polyunsaturated fatty acids, folic acid, hyaluronic acid, and oligopeptides are described as tumor- targeting moieties.
TL;DR: Using peptidomimetic antibodies to BBB transcytosis receptor, brain-targeted pegylated immunonanoparticles can now be synthesized that should make possible the delivery of entrapped actives into the brain parenchyma without inducing BBB permeability alteration.
Abstract: Nanoparticle drug carriers consist of solid biodegradable particles in size ranging from 10 to 1000 nm (50–300 nm generally). They cannot freely diffuse through the blood-brain barrier (BBB) and require receptor-mediated transport through brain capillary endothelium to deliver their content into the brain parenchyma. Polysorbate 80-coated polybutylcyano-acrylate nanoparticles can deliver drugs to the brain by a still debated mechanism. Despite interesting results these nanoparticles have limitations, discussed in this review, that may preclude, or at least limit, their potential clinical applications. Long-circulating nanoparticles made of methoxypoly(ethylene glycol)-polylactide or poly(lactide-co-glycolide) (mPEG-PLA/PLGA) have a good safety profiles and provide drug-sustained release. The availability of functionalized PEG-PLA permits to prepare target-specific nanoparticles by conjugation of cell surface ligand. Using peptidomimetic antibodies to BBB transcytosis receptor, brain-targeted pegylated immunonanoparticles can now be synthesized that should make possible the delivery of entrapped actives into the brain parenchyma without inducing BBB permeability alteration. This review presents their general properties (structure, loading capacity, pharmacokinetics) and currently available methods for immunonanoparticle preparation.
TL;DR: The results show that sonication time, PLGA and drug amounts, PVA concentration, ratio between aqueous and organic phases, and the method of solvent evaporation have a significant influence on size distribution of the nanoparticles.
TL;DR: The drug in vitro release behavior from NLC displayed biphasic drug release pattern with burst release at theInitial stage and prolonged release afterwards, and the successful control of release rate at the initial stage can be achieved by controlling OA content.
TL;DR: The tetrazolium dye method (MTT assay) using human pharyngeal cancer cells (KB cell) revealed that FMA significantly improved cell growth inhibitory activity in spite of a short exposure time due to the selective and strong interaction between folate molecules and their receptors.
Abstract: A new type of multifunctional polymeric micelle drug carrier for active intracellular drug delivery was prepared and characterized in this study. The micelle is a nano-supramolecular assembly with a spherical core-shell structure, and its surface and core were modified with piloting molecules for cancer cells and pH-sensitive drug binding linkers for controlled drug release, respectively. In order to prepare such micelles, self-assembling amphiphilic block copolymers, folate-poly(ethylene glycol)-poly(aspartate hydrazone adriamycin) [Fol-PEG-P(Asp-Hyd-ADR)], were specially designed and synthesized by installing a molecular promoter to enhance intracellular transport, folate (Fol), at the end of the shell-forming PEG chain and conjugating the anticancer drug, adriamycin (ADR), to the side chain of the core-forming PAsp segment through an acid-sensitive hydrazone bond. Because folate-binding proteins (FBP) are selectively overexpressed on the cancer cell membranes, the folate-bound micelles (FMA) can be guided to the cancer cells in the body, and after the micelles enter the cells, hydrazone bonds are cleaved by the intracellular acidic environment (pH 5-6) so that the drug release profile of the micelles is controlled pH-dependently. In this regard, FBP-binding selectivity of the prepared FMA was evaluated by surface plasmon resonance (SPR) measurements. The tetrazolium dye method (MTT assay) using human pharyngeal cancer cells (KB cell) revealed that FMA significantly improved cell growth inhibitory activity in spite of a short exposure time due to the selective and strong interaction between folate molecules and their receptors. Subsequent flow cytometric analysis showed that cellular uptake of FMA significantly increased. Consequently, these findings would provide one of the most effective approaches for cancer treatment using intracellular environment-targeting supramolecular drug carriers.
TL;DR: A method for measuring levels of bioavailable (released) doxorubicin in vivo in tumors that will allow therapeutic activity to be correlated with bioavailable drug levels and will help in the rational design of drug carriers is developed.
Abstract: Purpose: Pharmacokinetic studies on liposomal drugs have previously measured total drug levels in tumors, which include nonbioavailable drug However, drugs must be released from liposomes to have activity We have developed a method for measuring levels of bioavailable (released) doxorubicin in vivo in tumors that will allow therapeutic activity to be correlated with bioavailable drug levels Experimental Design: Mice orthotopically implanted with mammary carcinoma (4T1) were injected iv 10 days after implantation with free doxorubicin or formulations of liposomal doxorubicin with different drug release rates Tumors were excised at various times after injection, and total tumor doxorubicin levels were determined by acidified isopropanol extraction of whole tumor homogenates Bioavailable doxorubicin levels were determined by extraction of doxorubicin from isolated tumor nuclei Results: Free doxorubicin had high levels of bioavailability in tumor tissue; 95% of the total doxorubicin in tumors was bound to nuclear DNA by 24 hours after injection Administration of Doxil, a slow release liposomal formulation of doxorubicin, gave an area under the time-versus-concentration curve (AUC) for total doxorubicin 7 days after injection that was 87-fold higher than that obtained for free doxorubicin, and 49% of the liposomal doxorubicin was bioavailable For liposomes with a more rapid doxorubicin release rate, by 7 days after injection, the AUC 0-7 days for total doxorubicin was only 14-fold higher than that for free doxorubicin and only 27% of liposomal doxorubicin was bioavailable Conclusions: This technique allows correlations to be made between drug bioavailability and therapeutic activity and will help in the rational design of drug carriers
TL;DR: It is demonstrated that oxidized single- wall carbon nanohorns (SWNHs), a type of single-wall nanotube, entrap cisplatin, an anticancer agent, and are thus a potential drug delivery system.
Abstract: We demonstrate that oxidized single-wall carbon nanohorns (SWNHs), a type of single-wall nanotube, entrap cisplatin, an anticancer agent. We found that the cisplatin structure was maintained inside the SWNHs and that the cisplatin was slowly released from the SWNHs in aqueous environments. The released cisplatin was effective in terminating the growth of human lung-cancer cells, while the SWNHs themselves had no such effect. Cisplatin-incorporated oxidized SWNHs are thus a potential drug delivery system. Keywords: Carbon nanotube; carbon nanohorn; anticancer drug; drug carrier; cisplatin
TL;DR: This chapter will discuss the various methods for encapsulation of doxorubicin into liposomes, as well as some of the important interactions between the formulation components of the drug and how this may impact the biological activity of the associated drug.
Abstract: Doxorubicin is the best known and most widely used member of the anthracycline antibiotic group of anticancer agents. It was first introduced in the 1970s, and since that time has become one of the most commonly used drugs for the treatment of both hematological and solid tumors. The therapy-limiting toxicity for this drug is cardiomyopathy, which may lead to congestive heart failure and death. Approximately 2% of patients who have received a cumulative (lifetime) doxorubicin dose of 450-500 mg?m(2) will experience this condition. An approach to ameliorating doxorubicin-related toxicity is to use drug carriers, which engender a change in the pharmacological distribution of the drug, resulting in reduced drug levels in the heart. Examples of these carrier systems include lipid-based (liposome) formulations that effect a beneficial change in doxorubicin biodistribution, with two formulations approved for clinical use. Drug approval was based, in part, on data suggesting that beneficial changes in doxorubicin occurred in the absence of decreased therapeutic activity. Preclinical (animal) and clinical (human) studies showing that liposomes can preferentially accumulate in tumors have provided a rationale for improved activity. Liposomes represent ideal drug delivery systems, as the microvasculature in tumors is typically discontinuous, having pore sizes (100-780 nm) large enough for liposomes to move from the blood compartment into the extravascular space surrounding the tumor cells. Liposomes, in the size range of 100-200 nm readily extravasate within the site of tumor growth to provide locally concentrated drug delivery, a primary role of liposomal formulation. Although other liposomal drugs have been prepared and characterized due to the potential for liposomes to improve antitumor potency of the encapsulated drug, the studies on liposomal doxorubicin have been developed primarily to address issues of acute and chronic toxicity that occur as a consequence of using this drug. It is important to recognize that research programs directed toward the development of liposomal doxorubicin occurred concurrently with synthetic chemistry programs attempting to introduce safer and more effective anthracycline analogues. Although many of these drugs are approved for use, and preliminary liposomal formulations of these analogues have been prepared, doxorubicin continues to be a mainstay of drug cocktails used in the management of most solid tumors. It will be of great interest to observe how the approved formulations of liposomal doxorubicin are integrated into combination regimes for treatment of cancer. In the meantime, we have learned a great deal about liposomes as drug carriers from over 20 years of research on different liposomal doxorubicin formulations, the very first of which were identified in the late 1970s. This chapter will discuss the various methods for encapsulation of doxorubicin into liposomes, as well as some of the important interactions between the formulation components of the drug and how this may impact the biological activity of the associated drug. This review of methodology, in turn, will highlight research activities that are being pursued to achieve better performance parameters for liposomal formulations of doxorubicin, as well as other anticancer agents being considered for use with lipid-based carriers.
TL;DR: Both CS-coated systems (nanocapsules and CS- coated nanoparticles) showed an important capacity to enhance the intestinal absorption of the model peptide, salmon calcitonin, as shown by the important and long-lasting decrease in the calcemia levels observed in rats.
TL;DR: It is concluded that chitosan-alginate multilayer beads, cross-linked with polyphosphate offer an opportunity for controlled gastrointestinal passage of compounds with low molecular weight like ampicillin.
TL;DR: Ultrafine fibers containing water-soluble drugs were successfully electrospun from water-in-oil (W/O) emulsions, in which the aqueous phase contained the water- soluble drugs and the oily phase was a chloroform solution of amphiphilic poly (ethylene glycol)-poly (L-lactic acid) (PEG-PLLA) diblock copolymer.
TL;DR: To detect the mucoadhesive phenomena in the intestinal tract, the rat intestine was observed with the confocal laser scanning microscope (CLSM) after oral administration of the particulate systems and showed a longer retention of submicron-sized chitosan-coated liposomes (ssCS-Lip) in the intestine than other liposomal particles tested.
TL;DR: The effectiveness of conventional and deformable vesicles as drug delivery systems as well as their possible mode of action as permeation enhancers or transdermal drug carriers will be discussed.
TL;DR: The results of a comprehensive in vivo study of a novel tumor-targeting modality based on the encapsulation of the chemotherapeutic agent within polymeric micelles in combination with a local ultrasonic irradiation of the tumor are reported.
TL;DR: This review discusses nanoparticular drug carrier systems with the exception of liposomes used today, and what the potential and limitations of nanoparticles in the field of pharmaceutical biotechnology are.
Abstract: Nanotechnology, or systems/devices manufactured at the molecular level, is a multidisciplinary scientific field undergoing explosive development. A part of this field is the development of nanoscaled drug delivery devices. Nanoparticles have been developed as an important strategy to deliver conventional drugs, recombinant proteins, vaccines and more recently nucleotides. Nanoparticles and other colloidal drug delivery systems modify the kinetics, body distribution and drug release of an associated drug. Other effects are tissue or cell specific targeting of drugs and the reduction of unwanted side effects by a controlled release. Therefore nanoparticles in the pharmaceutical biotechnology sector improve the therapeutic index and provide solutions for future delivery problems for new classes of so called biotech drugs including recombinant proteins and oligonucleotides. This review discusses nanoparticular drug carrier systems with the exception of liposomes used today, and what the potential and limitations of nanoparticles in the field of pharmaceutical biotechnology are.
TL;DR: The utility of macromolecules in drug delivery is discussed and the numerous modalities currently available for achieving effective intracellular drug delivery are described, with a focus on cell-penetrating peptides.
TL;DR: FTIR imaging shows great promise in its ability to visualize the drug and excipient distribution in pharmaceutical formulations such as tablets and therapeutic transdermal systems, as well as to reveal the mechanism of drug release.
TL;DR: The designed system, combining excellent buoyant ability and suitable drug release pattern, could possibly be advantageous in terms of increased bioavailability of repaglinide.
TL;DR: The authors evaluated the chemotherapeutic potential of nebulized solid lipid particles (SLPs) incorporating rifampicin, isoniazid and pyrazinamide against experimental tuberculosis.