温度%2fpH双敏共聚物胶束的制备及体内药动学研究☆.pdfVIP

温度/pH双敏共聚物胶束的制备及体内药动学研究☆ 1, 2 1 1 1 1 1 1 贾莉 ，乔明曦 ，刘辉 ，祁嘉维 ，胡海洋 ，赵秀丽 ，陈大为 (1 沈阳药科大学药学院，辽宁沈阳，110016 2 菏泽医学专科学校，山东菏泽，274000) 摘要：目的 以两亲性共聚物聚组氨酸-聚乳酸羟基乙酸-聚乙二醇-聚乳酸羟基乙酸-聚组氨酸 （PHis-b-PLGA-b-PEG-b-PLGA-b-PHis ）为载体，pH/温度响应阿霉素胶束，并对其进行体外及体内药动 学评价。方法 采用透析法制备阿霉素胶束，测定其粒径、形态、载药量、包封率，透析法考察载药聚 合物胶束的体外释放行为，采用 HPLC-MS/MS 法研究了阿霉素在大鼠体内的药物代谢动力学。结果 DOX 胶束粒径为 130.1 nm，具有类球形结构，载药量为 13.3 %，包封率为 76.8% 。体外释放行为表明， 胶束释药具有 pH/温度响应性质，大鼠体内药动力学结果表明，共聚物胶束延长了阿霉素的体内循环时 间，与溶液剂相比，显著提高了 AUC 。结论 PHis-b-PLGA-b-PEG-b-PLGA-b-PHis 共聚物胶束作为疏水 性抗肿瘤药物的给药系统具有良好的应用前景。 关键词：阿霉素；PHis-b-PLGA-b-PEG-b-PLGA-b-PHis ；pH/温度响应；药物代谢动力学。 Preparation and Research on pharmacokinetic of Doxorubicin Loaded temperature/pH sensitive block copolymer micelles 1, 2 1 1 1 1 1 1 JIA Li , QIAO Ming-xi , LIU Hui , QI Jia-wei , HU Hai-yang , ZHAO Xiu-li , CHEN Da-wei 1 School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China 2 Heze Medical Colleges, Heze, Shandong 27400, China ABSTRACT: OBJECTIVE To prepare doxorubicin loaded temperature and pH sensitive PHis-PLGA-PEG-PLGA-PHis block copolymers micelles and to evaluate the drug loaded micelles in vitro and in vivo. METHODS The dialysis method was employed to prepare doxorubicin (DOX) loaded micelles. The morphology, diameter, the entrapment rate and drug-loading rate of DOX micelles were determined. The in vitro release study was further performed to study the temperature- and pH- responsive drug release behavior from DOX-loaded micelles. HPLC/MS/MS method was developed and applied to study the pharmacokinetic behavior of Doxorubicin-loaded block copolymer micelles in rats. RE