pH敏感的AB_4型嵌段共聚物的合成、表征与自组装行为

Preparation and characterization of pH-sensitive AB_4-type block copolymers with self-assembly

设计合成了一种AB4型pH敏感双亲嵌段共聚物。该共聚物由pH敏感的聚甲基丙烯酸及聚乳酸链段组成，其制备过程是先由端羟基聚乳酸与二氯乙酰氯通过酯化反应制得端四氯代聚乳酸，然后通过甲基丙烯酸叔丁酯的原子转移自由基聚合反应制得AB4型甲基丙烯酸叔丁酯一乳酸共聚物，再酸性水解。该共聚物可自组装为临界胶束浓度为19．7～32．5mg／L、流体力学直径小于200nm的球形核一壳胶束。该胶束表现出pH敏感性，其对紫杉醇在pH=5．6～7．4的缓冲溶液比在PH=1．4的缓冲溶液中有更快的释放速率，可作为疏水药物靶向释放的载体用于肠癌的靶向治疗。

AB4-type pH-sensitive arnphiphilic block copolymers, consisted of pH-sensitive poly- methacrylic acid and polylactic acid segments were synthesized in three steps. Firstly, Chloro- polyaetic acid （Cl2-PLA-C12） was prepared by esterification of HO-PLA-OH and CHC12 COC1. Then, poly （ t-butyl methacrylate ）-block-polylactic acid-block-poly （ t-butyl methacrylate ） （PtBMAz-b-PLA-b-PtBMAz） was synthesized via atom transfer radical polymerization. After hy- drolysis, polymethacry PMAAz） was obtained ic acid-block-polylactic acid-block-polymethacrylic acid （PMAA2-b-PLA-b- The copolymers could be spontaneously assembled into spherical core- shell micelles with critical micelle concentration （CMC） of about 19.7~32.5 mg/L and the hy- drodynamic diameters below 200 nm. The copolymer micelles exhibited pH sensitivity,and pacli- taxel had faster release rate in PBS solution at pH 5.6～7.4 than in PBS at pH 1.4. The copoly- mers may be used as water-insoluble drug targeting release carriers for intestine cancers.