Showing papers on "Drug carrier published in 1999"
Journal Article•
TL;DR: There are many potential barriers to the effective delivery of a drug in its active form to solid tumors, and small-molecule chemotherapeutic agents have a large volume of distribution on i.v. administration.
Abstract: There are many potential barriers to the effective delivery of a drug in its active form to solid tumors. Most small-molecule chemotherapeutic agents have a large volume of distribution on i.v. administration ([Speth et al., 1988][1]; [Chabner and Longo, 1996][2]). The result of this is often a
1,337 citations
TL;DR: This review examines the chemical nature of polymeric micelles as well as the methods used to characterize them with regard to drug delivery and potential medical applications, especially in cancer chemotherapy, are described and discussed.
1,200 citations
TL;DR: It was found that an aqueous phase pH of 9.3, replacement of procaine hydrochloride with procaine dihydrate and the incorporation of PMMA-MA, lauric and caprylic acid into the formulation could enhance drug incorporation efficiency without the size, morphology and nanoparticle recovery being adversely influenced.
978 citations
TL;DR: It is shown that diffusion controlled delivery of proteins from hydrogels containing poly(ethylene glycol) (PEG) can be possible and controlled by the three-dimensional structure.
567 citations
TL;DR: Polymeric micelles incorporated with adriamycin showed a dramatic thermo-responsive on/off switching behavior for both drug release and in vitro cytotoxicity according to the temperature responsive structural changes of a micellar shell structure.
553 citations
TL;DR: The results of the encapsulation efficiency analysis demonstrated that more lipophilic drugs, such as cyclosporin and indomethacin, do not suffer from the problems of drug leakage to the external medium, resulting in improved drug content in the nanoparticles.
Abstract: The purpose of this study was to assess the relative advantages and drawbacks of the nanoprecipitation–solvent displacement method for a range of drugs with respect to the particle size and drug encapsulation in polylactic-co-glycolic acid (PLGA) nanoparticles. The particle size analysis indicated a unimodal particle size distribution in all systems, with a mean diameter of 160–170 nm, except for insulin nanoparticles, which showed a smaller particle size. The results of the encapsulation efficiency analysis demonstrated that more lipophilic drugs, such as cyclosporin and indomethacin, do not suffer from the problems of drug leakage to the external medium, resulting in improved drug content in the nanoparticles. In spite of the fact that valproic acid is a liquid that is very sparingly soluble in water, very low encapsulation efficiency was obtained. Ketoprofen, a drug sparingly soluble in water, demonstrated intermediate values of encapsulation that were well correlated with its intermediate lipophilicit...
524 citations
TL;DR: It is demonstrated that the brain concentration of systemically administered doxorubicin can be enhanced over 60-fold by binding to biodegradable poly(butyl cyanoacrylate) nanoparticles, overcoated with the nonionic surfactant polysorbate 80.
Abstract: Purpose. To investigate the possibility of delivering of anticancer drugs into the brain using colloidal carriers (nanoparticles).
Methods. Rats obtained 5 mg/kg of doxorubicin by i v. injection in form of 4 preparations : 1. a simple solution in saline, 2. a simple solution in polysorbate 80 1% in saline, 3. bound to poly (butyl cyanoacrylate) nanoparticles, and 4. bound to poly(butyl cyanoacrylate) nanoparticles overcoated with 1% polysorbate 80 (Tween® 80). After sacrifice of the animals after 10 min, 1, 2, 4, 6, and 8 hours, the doxorubicin concentrations in plasma, liver, spleen, lungs, kidneys, heart and brain were determined after extraction by HPLC.
Results. No significant difference in the body distribution was observed between the two solution formulations. The two nanoparticle formulations very significantly decreased the heart concentrations. High brain concentrations of doxorubicin (>6 μg/g) were achieved with the nanoparticles overcoated with polysorbate 80 between 2 and 4 hours. The brain concentrations observed with the other three preparations were always below the detection limit (< 0.1 |μg/g).
Conclusions. The present study demonstrates that the brain concentration of systemically administered doxorubicin can be enhanced over 60-fold by binding to biodegradable poly(butyl cyanoacrylate) nanoparticles, overcoated with the nonionic surfactant polysorbate 80. It is highly probable that coated particles reached the brain intact and released the drug after endocytosis by the brain blood vessel endothelial cells.
517 citations
TL;DR: FA-targeted liposomes show enhanced nonspecific binding to extracellular tissue culture components, a phenomenon especially relevant in short incubation time experiments, and increasing the molecular mass of the PEG tether from 2000 to 3350 Da improved the FR binding, particularly in the case of mPEG-coatedliposomes.
479 citations
TL;DR: Results indicate that SLN are a promising sustained release and drug targeting system for lipophilic antitumour drugs, and may also allow a reduction in dosage and a decrease in systemic toxicity.
467 citations
TL;DR: DSC studies revealed that the H2 antagonist drug cimetidine was molecularly dispersed inside the microspheres, in the form of a solid solution, and the release of model drugs was fast, and accompanied by a burst effect.
460 citations
TL;DR: In an oral drug delivery system (DDS), the hydrophilic and ionizable CDs can serve as potent drug carriers in the immediate release- and delayed release-formulations, respectively, while the release rate of water-soluble drugs can be retarded by hydrophobic CDs.
TL;DR: P pH-responsive, poly(methacrylic-g-ethylene glycol) hydrogels are investigated as oral delivery vehicles for insulin to protect the sensitive drug from proteolytic degradation in the stomach and upper portion of the small intestine.
TL;DR: The study of the in vitro cytotoxicity of the nanoparticles revealed that the PEGylation of the cyanoacrylate polymer reduced its toxicity, which opens up interesting perspectives for the targeting of drugs to other tissues than the liver.
TL;DR: The effect of size on therapeutic activity (antitumor efficacy and toxicity) of a liposomal anticancer preparation is discussed and the importance of liposome size in the design of a more effective Liposomal antitumor Preparation is discussed.
TL;DR: A critique of the literature, the own work, and various simulations suggests that drug release from cyclodextrin complexes is rapid and quantitative in most cases.
TL;DR: In this paper, the effects of polymer morphology, composition and solute properties on transport behavior were investigated for water and drug transport in crosslinked polymeric materials, and two crosslinked polymer systems, poly(2-hydroxyethyl methacrylate) (P(HEMA-co-MMA)) and polyvinyl alcohol (PVA), were used in water transport and drug release experiments.
Journal Article•
TL;DR: The findings in the present study demonstrate a profound alteration of paclitaxel accumulation in erythrocytes caused by a trapping of the compound in CrEL micelles, thereby reducing the free drug fraction available for cellular partitioning.
Abstract: We have determined the in vitro and in vivo cellular distribution of the antineoplastic agent paclitaxel (Taxol) in human blood and the influence of Cremophor EL (CrEL), the vehicle used for i.v. drug administration. In the absence of CrEL, the blood:plasma concentration ratio was 1.07+/-0.004 (mean+/-SD). The addition of CrEL at concentrations corresponding to peak plasma levels achieved after the administration of paclitaxel (175 mg/m2 i.v. over a 3-h period; ie., 0.50%) resulted in a significant decrease in the concentration ratio (0.690+/-0.005; P plasma > human serum albumin, with CrEL present at or above the critical micellar concentration (approximately 0.01%). Our findings in the present study demonstrate a profound alteration of paclitaxel accumulation in erythrocytes caused by a trapping of the compound in CrEL micelles, thereby reducing the free drug fraction available for cellular partitioning. It is proposed that the nonlinearity of paclitaxel plasma disposition in patients reported previously should be reevaluated prospectively by measuring the free drug fractions and whole blood:plasma concentration ratios.
TL;DR: HA-Taxol conjugates showed selective toxicity toward the human cancer cell lines that are known to overexpress HA receptors, while no toxicity was observed toward a mouse fibroblast cell line at the same concentrations used with the cancer cells.
TL;DR: The ferrofluids potential was identified and its biological effects, its bioavailability and the in vivo desorption time of the anticancer drug epirubicin were identified and used in MDT treatment in mice and in man.
TL;DR: New hydrogels composed of poly(methacrylic acid) grafted with poly(ethylene glycol) (PEG) ( P(MAA-g-EG)) which can be used as drug delivery carriers for salmon calcitonin have been developed.
Abstract: pH-sensitive hydrogels are suitable candidates for oral drug delivery of peptides due to their ability to respond to their environment. We have developed new hydrogels composed of poly(methacrylic acid) (PMAA) grafted with poly(ethylene glycol) (PEG) (P(MAA-g-EG)) which can be used as drug delivery carriers for salmon calcitonin. P(MAA-g-EG) hydrogels were prepared by free radical solution polymerization. The monomer mixture was diluted using a 50% w/w solution of ethanol and water. The percentage of monomer in solution was varied from 84% to 45% v/v. Swelling studies were conducted to investigate the effects of solvent content used during polymer preparation in the swelling behavior. The effects of dilution on the swelling behavior were not observed until the monomer mixture was diluted to approximately 50%. Salmon calcitonin was successfully incorporated and released in vitro from the system. Solutions of approximately 0.1 mg/mL of salmon calcitonin were used to load the protein into the gels at pH = 7 ...
TL;DR: This review is to summarize recent findings and applications of various cyclodextrins in ophthalmic drug delivery and their mechanism of action in aqueous eye drop formulations.
TL;DR: This review focuses on literature appearing between January 1995-December 1997 that report antibody and receptor-mediated targeting approaches for improving drug localization and acid, enzymatic, thermal or photochemical triggering processes that destabilize membranes and improve drug bioavailability via cytoplasmic delivery of liposomal contents.
TL;DR: The results suggest that biodegradable PLGA microspheres can deliver intact and functional plasmid DNA at controlled rates and may be used to jointly deliver genes and other biologically active molecules, e.g., immunomodulators, to antigen presenting cells.
TL;DR: Transfer of anti‐CD19 into SIL resulted in a three‐fold increase in binding of these liposomes to CD19+ human B cell lymphoma cells.
TL;DR: It is concluded that PF127 gel formulations containing either drug or drug-nanoparticles could be useful for the preparation of a controlled delivery system for peptides and proteins having short half-lives using insulin as a model drug.
TL;DR: In this article, the critical substitution molar ratio of CDDP to Asp residues in PEG−P(Asp) to form a stable micelle structure was determined to be 0.5 and the CDDP-complexed micelle started to dissociate in approximately 10 h of the induction period accompanying the sustained release of platinum(II) complex from the micelle in physiological saline (0.15 M NaCl solution) at 37 °C.
Abstract: Block copolymer micelles (polymer−metal complex micelles) containing platinum(II) complexes in the core were prepared through the complexation of cis-dichlorodiammineplatinum(II) (cisplatin, CDDP) with poly(ethylene glycol)−poly(α,β-aspartic acid) block copolymer (PEG−P(Asp)) in an aqueous medium. Dynamic light scattering measurements revealed that CDDP-complexed micelles had diameters of approximately 20 nm with considerably narrow distribution. The critical substitution molar ratio of CDDP to Asp residues in PEG−P(Asp) (CDDP/Asp) to form a stable micelle structure was determined to be 0.5. The CDDP-complexed micelle, which was stable in distilled water at room temperature, started to dissociate in approximately 10 h of the induction period accompanying the sustained release of platinum(II) complex from the micelle in physiological saline (0.15 M NaCl solution) at 37 °C. The release rate of CDDP was inversely correlated with the chain length of P(Asp) segments in the block copolymer. This property of sus...
TL;DR: The conjugation approach of doxorubicin to PLGA was potentially useful for nanoparticle formulations that require high drug loading and sustained release.
Abstract: Purpose. Doxorubicin was chemically conjugated to a terminal end group of poly(D,L-lactic-co-glycolic acid) [PLGA] and the doxorubicin-PLGA conjugate was formulated into nanoparticles to sustain the release of doxorubicin.
Journal Article•
TL;DR: Although both liposomal groups were better than the free drug group in terms of clinically relevant parameters, including toxicity, tumor shrinkage, and survival, there was no difference between the twoliposomal drug groups.
Abstract: Sterically stabilized liposome is characterized by a surface coating of polyethylene glycol (PEG) or other polymers that can reduce opsonization of the liposome by plasma proteins. It has a higher plasma area under the concentration-time curve (AUC), which is believed to correlate with better therapeutic efficacy. However, the presence of large molecules on the liposomal surface may reduce the interactions of liposomes with cells and hinder entry of liposomes into the tumor tissue. Using a stable liposomal system composed of distearoyl phosphatidylcholine/cholesterol, we examined the effect of PEG (Mr 2000) on the pharmacokinetics and on the efficacy of liposomal doxorubicin with C-26 syngeneic tumor model in BALB/c mice. The plasma AUC of liposomal doxorubicin with 6 mol-% PEG-modified distearoyl phosphatidylethanolamine (PEG-DSPE) was approximately twice that of liposomal doxorubicin without PEG at various dosages, regardless of whether the mice were tumor-bearing. Paradoxically, the group of mice treated with liposomal doxorubicin without PEG had higher tumor doxorubicin concentrations. The 72-h tumor AUC was 1.44 times that of liposomal doxorubicin with 6% PEG-DSPE. The tumor-accumulation efficiency (AUC(Tumor)/AUC(Plasma)) of liposomal doxorubicin without PEG was 0.87, and this was more than twice that of the liposomal doxorubicin with 6% PEG-DSPE (0.31). At a dose of 10 mg/kg, although both liposomal groups were better than the free drug group in terms of clinically relevant parameters, including toxicity, tumor shrinkage, and survival, there was no difference between the two liposomal drug groups. In this stable liposome system, surface coating with PEG offered no benefit for liposomal doxorubicin in the C-26 tumor model. To enhance the therapeutic index of liposomal doxorubicin, simply increasing plasma AUC by surface coating with PEG may not be satisfactory.
TL;DR: PEG-PLA micelles have a considerably low critical association concentration (approximately 1.0 mg/l) which is apparently an advantage in utilizing these micells as drug carriers in an extremely diluted condition.