阿霉素温度/pH双敏型自组装嵌段共聚物胶束的制备

本文用透析法制备了新型温度/pH双敏自组装嵌段共聚物聚组氨酸-聚乳酸羟基乙酸-聚乙二醇-聚乳酸羟基乙酸-聚组氨酸 (OLH-b-PLGA-b-PEG-b-PLGA-b-OLH) 胶束, 采用荧光探针技术测定其不同温度下临界胶束浓度 (CMC); 用透析法测定共聚物胶束的包封率和载药量; 对胶束的粒径、形态和表面电位进行考察, 并对阿霉素胶束的体外释药和pH敏感性进行了研究。CMC介于0.022 4～0.001 7 μg·mL^?1, 胶束包封率为92.8%, 载药量为15.7%; 载药胶束粒径为 (61.7 ± 13.4) nm, zeta电位为?9.88 mV; 阿霉素的体外释药速率随pH降低 (pH 7.4～5.0) 而增加。结果表明, 胶束的CMC随温度升高而降低, 体外释药具有明显的pH敏感性, 该载体材料作为抗肿瘤药物的靶向传递系统具有较好的应用前景。

Preparation of adriamycin-loaded temperature/pH sensitive self-assembly block copolymer micelles

The dialysis method was employed to load adriamycin into the micells formed by temperature  and pH sensitive polyhistidine-co-DL-lactide-co-glycolide-polyethylene glycol poly DL-lactide-co-glycolide-co- histidine (OLH-b-PLGA-b-PEG-b-PLGA-b-OLH).  The critical micelle concentration (CMC) of the copolymer was measured with pyrene fluorescent probe method under different temperatures.  The entrapment rate and drug-loading rate were determined with dialysis method.  The diameter, morphology and surface potential of the copolymer micelles were investigated by corresponding instruments, respectively.  The release behavior of adriamycin from copolymer micelles and the pH sensitivity were studied.  The CMC of the copolymers ranged from 0.022 4 to 0.001 7 μg·mL⁻¹.  The entrapment rate and drug-loading rate were 92.8% and 15.7%, respectively.  The micelles have a mean diameter of (61.7 ± 13.4) nm, and zeta potential was −9.88 mV.  The in vitro adriamycin release rate increased with the pH dropping from 7.4 to 5.0.  The results indicated that the CMC of the copolymers  decreased as the raising of temperature, drug release behavior from the micells possessed clearly pH sensitivity, and the copolymers may have a potential in targeted delivery system for anticancer drugs.