Synthesis and Characterization of Amphiphilic Triblock Copolymers and Their Design for Drug Carriers

• Main Authors: Juang, lee-wei, 莊禮維
• Other Authors: Wen-jen Lin
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/40608765648044380158

碩士 === 國立臺灣大學 === 藥學研究所 === 90 === Recently, biodegradable amphiphilic block copolymers have become attractive in both fundamental and applied fields of polymer science. Amphiphilic block copolymers are assembled in aqueous media to form polymer micelles with a core-shell structure. Polymeric micelles based on biodegradable amphiphilic block copolymers have shown promise as drug carriers for parenteral delivery systems. In our study, the amphiphilic triblock copolymers, were synthesized by a ring opening polymerization of lactone monomers (e-caprolactone、d-valerolactone and L-lactide) initiated with hydroxy-teriminated polyethylene glycols without any catalysts. Two series of copolymers were prepared using poly(ethylene glycol)s with different molecular weights (PEG4000 and PEG10000) and varying the initial molar ratio of lactone monomers to PEG. The resulting copolymers were characterized by 1H-NMR, gel permeation chromatography (GPC), fourier-transform infrared spectroscopy (FT-IR), wide-angle X-ray diffraction (WAXD), and differential scanning calorimerty (DSC). The critical micelle concentrations (CMC) were measured by fluorescence probe technique using pyrene as the fluorescent dye. Using the resulting amphiphilic triblock copolymers, we prepared polymeric micelles entrapped with hydrophobic model drug- indomethacin in the inner core by dialysis method, and the release studies were performed in phosphate buffer solution (pH 7.2) at 37℃. The amphiphilic triblock copolymers were successfully synthesized with varying molar composition of lactone monomers and PEG in the absence of catalysts. The number-average molecular weights of synthesized copolymers were between 4,600 and 31,312 dalton with a unimodal molecular weight distribution. The CMC values were below 1.06×10-6 mol/L and dependent on the chain length of hydrophobic blocks. The size of drug-loaded micelles was less than 150 nm and had a nice spherical shape. The drug loading efficiency was in the range of 2.67 % ~ 100.42 %. In vitro release experiments showed that the release of indomethacin from micelles exhibited a sustained release behavior. The release profiles indicate that the percentage of drug release could be tailored by adjusting the composition of amphiphilic triblock copolymers. We suggest the amphiphilic triblock copolymers might be used as a hydrophobic drug carrier in the drug delivery systems.