1,721,060 research outputs found
Biodegradable nanoparticles containing protein-fatty acid complexes for oral delivery of salmon calcitonin
No full textBiodegradable nanoparticles containing salmon calcitonin (sCT) were formulated using protein-fatty acid complexes, and their in vitro transport against a Caco-2 cell monolayer and the extent of in vivo oral uptake were assessed. Positively charged sCT was hydrophobically ion paired to form physical complexes with fatty acid, phospholipid, and surfactant. Among the complexes, sodium oleate was used to form sCT-oleate complexes, which were characterized and formulated into biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Endocytosis of sCT nanoparticles by Caco-2 cells was studied by flow cytometry. Transcytosis of sCT across the Caco-2 monolayer was also quantitated by an ELISA method. The sCT nanoparticles were orally administered to Sprague-Dawley rats, and serum sCT was monitored. Biodegradable polymeric nanoparticles containing a loading amount of sCT as high as 2.7% (w/w) were prepared based on the complexation of sCT with sodium oleate. A greater amount of sCT nanoparticles could be delivered into Caco-2 cells compared with free sCT, and sCT could also be transported from the apical side to the basolateral side of the Caco-2 monolayer. In vivo experiments using a rat animal model showed the possibility of oral uptake of sCT. This study showed that physical complexation of sCT with amphiphilic molecules enabled the formation of sCT-loaded PLGA nanoparticles at a high loading efficiency and that sCT-PLGA nanoparticles were transported across the Caco-2 cell monolayer and were readily taken up in vivo following oral admistration. (C) 2004 Wiley-Liss, Inc.Dong Kuk
Pharmaceutical Company and by the Ministry of
Science and Technology, Kore
Folate-receptor-targeted delivery of doxorubicin nano-aggregates stabilized by doxorubicin-PEG-folate conjugate
No full textFor folate-receptor-targeted. anti-cancer therapy, doxorubicin aggregates in a nano-scale size were produced employing doxorubicin-polyethylene glycol-folate (DOX-PEG-FOL) conjugate. Doxorubicin and folate were respectively conjugated to alpha- and omega-terminal end group of a PEG chain. The conjugates assisted to form doxorubicin nano-aggregates with an average size of 200 nm in diameter when combined with an excess amount of deprotonated doxorubicin in an aqueous phase. Hydrophobically deprotonated doxorubicin molecules were aggregated within the core, while the DOX-PEG-FOL conjugates stabilized the aggregates with exposing folate moieties on the surface. The doxorubicin nano-aggregates showed a greater extent of intracellular uptake against folate-receptor-positive cancer cells than folate-receptor-negative cells, indicating that the cellular uptake occurred via a folate-receptor-mediated endocytosis mechanism. They also exhibited more potent cytotoxic effect on KB cells than free doxorubicin. In a human tumor xenograft nude mouse model, folate-targeted doxorubicin nano-aggregates significantly reduced the tumor volume compared to non-targeted doxorubicin aggregates or free doxorubicin. These results suggested that folate-targeted doxorubicin nano-aggregates could be a potentially useful delivery system for folate-receptor-positive cancer cells. (C) 2004 Elsevier B.V. All rights reserved.the Ministry of
Science and Technology (M1021400017-02b1500-
02110), Republic of Korea
Folate receptor targeted biodegradable polymeric doxorubicin micelles
No full textBiodegradable polymeric micelles, self-assembled from a di-block copolymer of poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG), were prepared to achieve folate receptor targeted delivery of doxorubicin (DOX). In the diblock copolymer structure of PLGA-b-PEG, DOX was chemically conjugated to a terminal end of PLGA to produce DOX-PLGA-mPEG, and folate was separately conjugated to a terminal end of PEG to produce PLGA-PEG-FOL. The two diblock copolymers with different functional moieties at their chains ends were physically mixed with free base DOX in an aqueous solution to form mixed micelles. It was expected that folate moieties were exposed on the micellar surface, while DOX was physically and chemically entrapped in the core of micelles. Flow cytometry and confocal image analysis revealed that folate conjugated mixed micelles exhibited far greater extent of cellular uptake than folate unconjugated micelles against KB cells over-expressing folate receptors on the surface. They also showed higher cytotoxicity than DOX, suggesting that folate receptor medicated endocytosis of the micelles played an important role in transporting an increased amount of DOX within cells. In vivo animal experiments, using a nude mice xenograft model, demonstrated that when systemically administered, tumor volume was significantly regressed. Biodistribution studies also indicated that an increased amount of DOX was accumulated in the tumor tissue. (C) 2004 Elsevier B.V. All rights reserved.the Ministry of
Science and Technology (M1021400017-02b1500-
02110), Republic of Korea
Enhanced photoluminescence of a hybrid luminescent film infiltrated into a colloidal photonic crystal
No full textDoxorubicin-conjugated biodegradable polymeric micelles having acid-cleavable linkages
No full textDoxorubicin was chemically conjugated to the terminal end of a di-block copolymer composed of poly(L-lactic acid) (PLLA) and methoxy-poly(ethylene glycol) (mPEG) via two acid-cleavable linkages. A hydrazone bond and a cis-acotinyl bond were formed between doxorubicin and the terminal group of PLLA segment in the block copolymer. Doxorubicin-conjugated PLLA-mPEG di-block copolymers self-assembled to form micelles in aqueous solution. The doxorubicin-conjugated micelles were about 89.1 nm in diameter and their critical micelle concentration was 1.3 mug/ml. These values were comparable with those of unconjugated micelles. In an acidic condition, the conjugated doxorubicin in the hydrazone linkage was readily cleaved, releasing doxorubicin in an intact structure. Doxorubicin-conjugated PLLA-mPEG micelles were more potent in cell cytotoxicity than free doxorubicin, suggesting that they were more easily taken up within cells with concomitant rapid release of cleaved doxorubicin into the cytoplasm from acidic endosomes. (C) 2002 Elsevier Science B.V. All rights reserved.the Center for Advanced Functional Polymers, KAIST, Korea.
Protein-fatty acid complex for enhanced loading and stability within biodegradable nanoparticles
No full textLysozyme was hydrophobically modified with a fatty acid, sodium oleate, via an ion-pairing mechanism. Ionic binding between an anionic carboxylic group of sodium oleate and basic amino groups in lysozyme was primarily utilized to form lysozyme-oleate complex. The complex formation was pH dependent. The lysozyme-oleate complex dissolved in an organic solvent exhibited much higher conformational stability at elevated temperature compared with free lysozyme in the same solvent. The complex was formulated into biodegradable nanoparticles by a spontaneous emulsion and solvent diffusion method. The resultant formulation showed near 100% encapsulation efficiency of lysozyme within nanoparticles with < 100 nm in diameter with a narrow size distribution. Lysozyme could be loaded into the nanoparticles up to 18.6% (w/w) with concomitantly increased particle sizes. This study demonstrates a new formulation method of biodegradable nanoparticles with highly efficient encapsulation of proteins, which are potentially useful for oral protein delivery including mucosal vaccination. (C) 2001 Wiley-Liss, Inc.the Center for
Advanced Functional Polymers, KAIST
Optical properties of red-emitting thin film phosphor sputtered on silica microsphere photonic crystal layer
No full textFission yeast dihydrolipoamide dehydrogenase gene is involved in G(1)/S cell cycle progression
No full textUsing functional complementation with a Schizosaccharomyces pombe genomic library, we have isolated a clone complementing a G(1)/S phase progression defective mutant. The newly isolated temperature-sensitive mutant, cyj150, showed elongated morphology at a restrictive temperature of 36 degrees C and DNA content analysis of the mutant indicated a defect in cell cycle progression at the G(1)/S phase. Sequence analysis of the genomic and cDNA clones complementing this elongated phenotype at 36 degrees C show that it encodes a protein that has 50% amino acid identity with dihydrolipoamide dehydrogenase from Saccharomyces cerevisiae and garden pea. Alignment of the deduced amino acid sequence of S. pombe dihydrolipoamide dehydrogenase (dld1(+)) with glutathione reductase and mercuric reductase revealed extensive homologies throughout the primary sequence and protein structure, and contained amino acid sequences of the active site region conserved from prokaryote to higher eukaryote. Gene disruption and tetrad analysis showed that dld1(+) is an essential gene for cell viability. Northern analysis indicates that transcriptional expression of this gene is not fluctuated according to the cell cycle, However, it is certain that malfunction of this Dld1 protein blocks the progression of cell cycle from G(1) to S phase. The sequence of the dld1(+) gene is available in EMBL/GenBank under Accession Number L40360. (C) 1997 Elsevier Science B.V
Biodegradable polymeric micelles composed of doxorubicin conjugated PLGA–PEG block copolymer
No full textBiodegradable polymeric micelles containing doxorubicin in the core region were prepared from a di-block copolymer composed of doxorubicin-conjugated poly(DL- lactic-co-glycolic acid) (PLGA) and polyethyleneglycol (PEG). The di-block copolymer of PLGA-PEG was first synthesized and the primary amino group of doxorubicin was then conjugated to the terminal hydroxyl group of PLGA, which had been pre-activated using p-nitrophenyl chloroformate. The resulting polymeric micelles in aqueous solution were characterized by measurement of sizer drug loading, and critical micelle concentration. The micelles containing chemically-conjugated doxorubicin exhibited a more sustained release profile than PEG-PLGA micelles containing physically-entrapped doxorubicin. The cytotoxic activity of the micelles against HepG2 cells was greater than free doxorubicin. suggesting that the micelles containing conjugated doxorubicin were more effectively taken up cellularly, by an endocytosis mechanism rather than by passive diffusion. Confocal microscopic observation and Row cytometry analysis supported the enhanced cellular uptake of the micelles. (C) 2001 Elsevier Science B.V. All rights reserved.the Center for Advanced Functional Polymers, KAIST, Korea
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