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目的以p H敏感聚合物聚乙二醇-聚乳酸-聚组氨酸[poly(ethyleneglyco1)-poly(D,L-lactide)-poly(L-histidine),m PEG-PLA-PHis]胶束为载体,联合包载抗肿瘤药物阿霉素与多药耐药逆转剂五味子乙素制备聚合物胶束,并对其制剂学性质进行研究。方法采用薄膜分散法制备阿霉素-五味子乙素p H敏感聚合物胶束,以包封率、载药量和稳定性(载药胶束24 h的包封率和载药量变化)为评价指标,采用单因素试验及Box-Behnken效应面法筛选最优处方;应用透射电子显微镜观察载药胶束的外观形态,动态光散射法测定载药胶束的粒径及zeta电位;透析法考察载药胶束在不同p H条件下的释药行为。结果制备的阿霉素-五味子乙素p H敏感聚合物胶束平均粒径为64.73 nm,zeta电位为-8.7 m V。最优处方中阿霉素包封率为95.3%,载药量为8.7%,五味子乙素包封率为76.1%,载药量为3.4%,载药胶束稳定性较好。体外释放结果表明,所制备的阿霉素-五味子乙素p H敏感聚合物胶束在弱酸性条件下,药物释放速率明显加快。结论采用星点设计-效应面法优化处方与制备工艺,所制备的阿霉素-五味子乙素p H敏感聚合物胶束粒径分布均匀,包封率和载药量良好,具有明显的p H响应行为。
OBJECTIVE To investigate the effects of p H-sensitive polymer poly (ethyleneglyco1) -poly (L-histidine), m PEG-PLA-PHis micelles As the carrier, combined with drug-resistant doxorubicin and multidrug resistance reversal agent Schisandrin B preparation of polymer micelles, and the preparation of the study of its properties. Methods The doxorubicin-schisandrin B-sensitive polymer micelles were prepared by membrane dispersion method. The entrapment efficiency, drug loading and stability (encapsulation efficiency and drug loading of drug-loaded micelles 24 h) were The single factor test and the Box-Behnken effect surface method were used to screen the optimal formulation. The morphology of the drug-loaded micelles was observed by transmission electron microscopy, the particle size and zeta potential of drug-loaded micelles were determined by dynamic light scattering The release behavior of drug-loaded micelles under different pH conditions was investigated. Results The average diameter of the doxorubicin-schisandrin p H-sensitive polymer micelles was 64.73 nm and the zeta potential was -8.7 mV. The optimum formulation of doxorubicin encapsulation efficiency was 95.3%, drug loading was 8.7%, Schizandrin B encapsulation efficiency was 76.1%, drug loading was 3.4%, drug-loaded micelles stability is better. The results of in vitro release showed that the drug release rate of adriamycin-Schisandrin B-sensitive polymer micelles was significantly increased under mildly acidic conditions. Conclusion The method of star point design-response surface method was used to optimize the formulation and preparation process. The prepared doxorubicin-p H sensitive polymer micelles have uniform particle size, good entrapment efficiency and drug loading, and have obvious p H response behavior.