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

合成聚苹果酸苄基酯（PMLABz）和聚苹果酸（PMLA），在此基础上构建两种不同类型的聚合物胶柬，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），利用动态透析法制备P1、P2胶柬，并进行表征、筛选。为了进一步增强胶束细胞的内摄作用和特定肿瘤细胞的靶向性，用靶向分子叶酸修饰胶柬，结果显示，该方法能成功制备药物载体PMLABz、PMLA及共聚物P1、P2，其中，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胶柬是一种潜在的自组装给药体系。

Two types of CPT-conjugated self-assembled polymeric micelles were fabricated based on poly （β-L-malic acid）（PMLA） derivatives. Firstly, PMLABz, PMLA, Poly （ethylene glycol）-poly03-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 micelle were functionalized with folic acid moieties. The results indicates that P1 was a grafted copolyme, and could be formed star micelle in aqueous solution with diameter about 100 nm. And P2 was an amphiphilic block copolymer, and could be formed crew cut micelle with diameter about 75 nm. Thus, 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.