紫杉醇pH敏感嵌段共聚物胶束的制备与体外评价

Preparation and in vitro evaluation of paclitaxel-loaded copolymeric micelles

目的应用pH敏感聚组氨酸-聚乳酸-聚乙二醇(poly(L-histidine)-poly(D,L-lactide)-poly(ethylene glycol),PHis-PLA-mPEG)聚合物为载体材料,采用溶剂挥发法制备紫杉醇pH敏感嵌段共聚物胶束,并对其体外性质进行评价。方法采用芘荧光探针法测定PHis-PLA-mPEG聚合物的临界胶束浓度(critical micelle concentration,CMC);超速离心法测定紫杉醇共聚物胶束的包封率和载药量;分别利用动态光散射法和Zeta电位分析仪对胶束的粒径分布和表面电位进行测定;采用透析法测定载药胶束在不同pH条件下的体外释药行为。结果 PHis-PLA-mPEG临界胶束质量浓度为8.9 mg·L-1,胶束载药量质量分数为8%;包封率可达90%以上;载药胶束的平均粒径为150.2nm,PDI为0.097,粒度分布较窄,Zeta电位为-14.3 mV;载药胶束在弱酸性条件下,药物释放行为明显加快。结论 PHis-PLA-mPEG聚合物载体材料具有较好的pH敏感释药行为,其作为抗肿瘤药物的靶向传递系统具有较好的应用前景。

Objective To encapsulate paclitaxel by solvent evaporation method by using poly （L-histidine）- poly （ L-lactic acid） -mPEG （PHis-PLA-mPEG） block copolymer, and to study the physicochemical proper- ties of the micelles. Methods The critical micelle concentration （CMC） of the copolymers was measured with pyrene fluorescent probe technique. The particle size and zeta potential of the polymeric micelles were characterized by dynamic light scattering （DLS）. The entrapment rate and drug-loading rate were determined by ultracentrifugation. The in vitro release of paclitaxel （PTX） -loaded block polymeric micelles was evalua- ted under different pH conditions. Results The CMC, entrapment efficiency and drug loading amount of the micelles were 8.9 mg· L-1,90% and 8 % （w）, respectively. The average particle size of PTX loaded micelle was around 150. 2 nm with narrow size distribution. The in vitro release of PTX-loaded micelles suggests that the micelles accelerated drug release with the pH dropping from 7.4 to 5.0, indicating that the change of pH could affect the drug release. Conclusions The copolymers have demonstrated prominence in delivery system for poor water-soluble anticancer drugs.