基于β-聚苹果酸衍生物的两种聚合物胶束的制备  

Preparation of Two Types of Campotothecin-conjugated Polymeric Micelles Based on Poly （β-L-malic Acid） Derivatives as Drug Carriers

作　　者：李伟[1] 段晓[1] 范黎[1] 吴红[1] 

机构地区：[1]第四军医大学药学院药物化学与药物分析教研室,陕西西安710032

出　　处：《纳米科技》2013年第6期39-46,71,共9页

基　　金：Acknowledgements We greatly acknowledge the financial support from the National Natural Science Foundation of China （grant No. 30970788, No.81271687）.

摘　　要：合成聚苹果酸苄基酯（PMLABz）和聚苹果酸（PMLA），并以此为基础构建两种不同类型的聚合物胶束，通过合成PMLABz、PMLA、聚乙二醇-聚苹果酸-喜树碱-I（P1）和聚乙二醇-聚苹果酸-喜树碱-Ⅱ（P2），动态透析法制备P1、P2胶束，并进行表征、筛选。为了进一步增强胶柬的细胞内摄作用和特定肿瘤细胞靶向性，用靶向分子叶酸修饰胶柬。结果表明，成功地制备出药物载体PMLABz、PMLA及共聚物P1、P2。P1是接枝共聚物，能够自组装成平均直径100nm星型胶束（载药量：11.2％，粒径：97．2±4．6nm，zeta电位：-18．5mV）；P2是嵌段共聚物．能够自组装成平均直径75nm的平头型胶束（载药量：20．5％，粒径：76．4±3．8nm，zeta电位：-16．4mv）：P1、P2胶柬形态圆整，粒径均匀，因此，P1、P2胶束是一种潜在的自组装给药体系。Two types of CPT-conjugated self-assembled polymeric micelles were constructed based on poly （β-L-malic acid） （PMLA） derivatives. Firstly, PMLABz, PMLA, Poly （ethylene glycol） -poly （β-L-malic acid） -campotothecin-I （PEG-PMLA-CPT-I, P1） and PEG-PMLA-CPT-Ⅱ （P2） were synthetized and confirmed by ^1HNMR and FTIR. Then, P1 micelles and P2 micelles were prepared and characterized. In order to target selective tumor cells, P1 micelle and P2 mieelle were functionalized with folic acid moieties. The results showed that P1 was a grafted copolymer, and could be formed star micelle in aqueous solution with diameter about 100 nm. P2 was an amphiphilie block copolymer, and could be formed crew cut micelle with diameter about 75 nm. Therefore, P1 and P2 micelles could be used as a promising self- assembled drug delivery system and their biological evaluation will be further test and verify in vitro and in vivo.

关 键 词：聚苹果酸 喜树碱 聚合物胶束 自组装给药系统 

分 类 号：R284.3[医药卫生—中药学] R944.2[医药卫生—中医学]