聚乙二醇-聚乳酸共聚物胶束溶液的冷冻干燥及胶束体外释药动力学.PDF

2007 年第65 卷 化 学 学 报 Vol. 65, 2007 第19 期, 2169～2174 ACTA CHIMICA SINICA No. 19, 2169～2174 ·研究论文· 聚乙二醇-聚乳酸共聚物胶束溶液的冷冻干燥及胶束体外释药 动力学研究 杨卓理 李馨儒 杨可伟 刘 艳* (北京大学医学部药学院药剂学系 北京 100083) 摘要 合成了一系列亲水、疏水链段质量比例不同的聚乙二醇-聚乳酸(PEG-PLA)嵌段共聚物胶束, 并以两性霉素B 为 模型药物制备了载药胶束. 为获得稳定性良好的、可长期储存的载药胶束剂型, 对胶束进行了冷冻干燥. 使用不同浓度 的糖类(包括甘露糖、海藻糖、葡萄糖) 、泊洛沙姆188 (Pluronic F68)、聚乙二醇作为冻干保护剂, 以冻干产品的重分散 性、冻干前后胶束的粒径及多分散性为指标评价各种保护剂的保护效果. 结果发现, 当嵌段聚合物中聚乳酸链段的质 量百分比小于或等于聚乙二醇时, 糖类、Pluronic F68 和PEG 均可以起到有效的冻干保护作用; 而对于聚乳酸链段质量 比例较大的共聚物胶束, 只有PEG 和Pluronic F68 能够起到较好的冻干保护作用. 对载药胶束体外释放研究表明, 聚合 物胶束的体外释放缓慢, 符合一级动力学特征. 关键词 聚乙二醇-聚乳酸; 聚合物胶束; 两性霉素B; 冷冻干燥; 体外释放 Freeze-Drying and in vitro Release Kinetics of Poly(ethylene glycol)- Poly(dl-lactide) Block Copolymer Micelles YANG, Zhuo-Li LI, Xin-Ru YANG, Ke-Wei LIU, Yan* (Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100083) Abstract A series of poly(ethylene glycol)-poly(dl-lactide) (PEG-PLA) block copolymers with varying molecular weights were synthesized. Drug-loaded micelles were prepared using amphotericin B (AmB) as the model drug. The PEG-PLA copolymers were freeze-dried to obtain long-term stable formulations. Sac- charides at various concentrations including mannose, trehalose and glucose, Pluronic F68 and PEG were used as lyoprotectants, respectively. The protective effects of the various types of lyoprotectants on the par- ticle size and si