Yoo H S, Park T G
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305-701, South Korea.
J Control Release. 2001 Jan 29;70(1-2):63-70. doi: 10.1016/s0168-3659(00)00340-0.
Biodegradable 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 size, 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 flow cytometry analysis supported the enhanced cellular uptake of the micelles.
由核心区域含有阿霉素的可生物降解聚合物胶束是由一种二嵌段共聚物制备而成，该共聚物由阿霉素共轭的聚（DL-乳酸-乙醇酸）（PLGA）和聚乙二醇（PEG）组成。首先合成PLGA-PEG二嵌段共聚物，然后将阿霉素的伯氨基与PLGA的末端羟基共轭，PLGA的末端羟基已用对硝基苯基氯甲酸酯预活化。通过测量尺寸、载药量和临界胶束浓度对所得聚合物胶束在水溶液中的性质进行表征。含有化学共轭阿霉素的胶束比含有物理包裹阿霉素的PEG-PLGA胶束表现出更持久的释放曲线。胶束对HepG2细胞的细胞毒性活性大于游离阿霉素，这表明含有共轭阿霉素的胶束通过内吞作用机制而非被动扩散更有效地被细胞摄取。共聚焦显微镜观察和流式细胞术分析支持了胶束增强的细胞摄取。
