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化学学报
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化学学报 ›› 2007, Vol. 65 ›› Issue (19): 2169-2174. 上一篇    下一篇

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*   

  1. (北京大学医学部药学院药剂学系 北京 100083)
  • 投稿日期:2007-01-09 修回日期:2007-03-12 发布日期:2007-10-14
  • 通讯作者: 刘艳

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*   

  1. (Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100083)
  • Received:2007-01-09 Revised:2007-03-12 Published:2007-10-14
  • Contact: LIU Yan

PDF

1718

被引次数

40

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

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. Saccharides 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 particle size and size distribution during freeze-drying process and redispersion were investigated. The results indicated that the saccharides, Pluronic F68 and PEG all could stabilize the micellar particles in the lyophilization when the weight ratio of PLA block was smaller than that of PEG block. While the weight ratio of PLA block was bigger than that of PEG block, only steric stabilizers such as PEG and F68 were able to protect PEG-PLA micelles from the agglomeration in the freeze-drying procedure. The sustained in vitro release of AmB from PEG-PLA micelles was evidenced. The in vitro release behavior could be best described by the first order equation.

Key words: poly(ethylene glycol)-poly(dl-lactide), polymeric micelle, amphotericin B, lyophilization, in vitro release