阿霉素-五味子乙素pH敏感聚合物胶束的制备与制剂学性质  

Preparation and physicochemical properties of pH-sensitive polymeric micelles containing doxorubicin/shizandrin B

作　　者：周佳莹[1] 周立宏 张晓君[3] 乔明曦[3] 赵秀丽[3] 陈大为[3] 

机构地区：[1]沈阳药科大学中药学院,辽宁沈阳110016 [2]烟台鲁银药业有限公司,山东烟台264002 [3]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2016年第9期686-695,共10页Journal of Shenyang Pharmaceutical University

摘　　要：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 prepare pH-sensitive polymeric micelles using poly （ethyleneglycol）-poly （D, L- lactide）-poly （L-histidine） （mPEG-PLA-PHis）triblock copolymer for co-delivery of doxorubicin and shizandrin B and to investigate the physicochemical properties of the micelles. Methods The copolymer micelles were prepared by film dispersion method. The optimum formula and preparation process were developed using single factor experiment combined with central composite design response surface method, which were evaluated in terms of loading content, entrapment efficiency as well as stability of drug-loaded micelles （the change of loading content and entrapment efficiency in 24 h ）. The morphology was characterized by transmission electron microscopy （TEM）, while the particle size and zeta-potential of the polymeric micelles were measured by dynamic light scattering （DLS）. The in vitro release of drug-loaded copolymer micelles was evaluated under different pH conditions. Results The sizes and zeta-potential of drug loaded copolymer micelles were 64.73 nm and - 8.7 mV, and the encapsulation efficiency and loading content were 95.3% and 8.7% for doxorubicin,and 76.1% and 3.4% for shizandrin B ,respectively. The doxorubicin/shizandrin B loaded micelles showed good stability at room temperature. In vitro release results showed that the release of drug could be accelerated under acidic conditions, which indicated the pattern of pH responsive drug release. Conclusions The copolymer micelles containing doxorubicin and shizandrin B have been demonstrated to possess small particle size, uniform distribution, high encapsulation efficiency and loading content, moreover, and pH sensitive drug release pattern.

关 键 词：阿霉素 五味子乙素 聚乙二醇-聚乳酸-聚组氨酸 胶束 PH敏感 Box-Behnken效应面 

分 类 号：R94[医药卫生—药剂学]