目的 制备载紫杉醇pH敏感嵌段共聚物胶束,评价抗肿瘤细胞药效.方法 用ATRP和click反应合成聚己内酯-聚甲基丙烯酸-N,N-二乙氨基乙酯-聚乙二醇嵌段共聚物(PDC),制备聚合物胶束,测定不同pH条件下胶束粒径和zeta电位;包载紫杉醇,测定包封率和载药量;透析法考察胶束的体外释药行为;MTT法评价胶束对人乳腺癌细胞MCF-7的细胞毒性.结果 聚合物胶束的粒径和zeta电位随pH增大而减小.紫杉醇的包封率为92.0％,载药量为8.36％.中性环境中胶束粒径为100.3 nm,zeta电位接近零.在低pH值(pH 6.5)环境中胶束的释药速率比中性环境中快,累积释放率高,对肿瘤细胞生长抑制效果好.结论 pH敏感嵌段共聚物胶束有良好的pH敏感释药特点和抗肿瘤细胞药效,有望成为理想的抗肿瘤药物靶向载体.%Objective To prepare paclitaxel-loaded pH-sensitive block copolymer micelles and evaluate the in vitro anti-cancer effect. Methods A block copolymer, poly (e-caprolactone)-poly (N,N-diethylamino-2-ethylmethacrylate)-poly (ethylene glycol) (PDC) , was prepared by ATRP and click reactions and polymeric micelles were prepared. The sizes and zeta potentials of micelles were determined under varied pH values. Paclitaxel was encapsulated in the micelles. The encapsulation efficiency and loading efficiency were measured. Drug release was investigated using dialysis method. Human breast cancer MCF-7 cells were used to evaluate the anti-cancer effect of drug-loaded micelles by MTT method. Results The sizes and zeta potentials of micelles decreased with the increase of pH values. The drug encapsulation efficiency was 92. 0% and the loading efficiency was 8. 36% . Under neutral environment, the mean size was 100. 3 ran, and the zeta potential was close to zero. The micelles showed faster drug release, higher accumulation release, and better anti-cancer effect in the low pH (6.5) media than in the neutral media. Conclusion The pH-sensitive block copolymer micelles have the merits of pH-sensitive drug release and high anti-cancer effect. It is a promising anti-cancer drug earner.
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