紫杉醇混合胶束的制备及增强口服生物利用度研究  

Preparation of paclitaxel-loaded mixed micelles and enhancement on oral absorption of paclitaxel

作　　者：崔亚男[1] 葛建君[2] 李凌冰[1] 

机构地区：[1]山东大学药学院药物制剂与释药系统研究中心,济南250012 [2]枣庄科技职业学院,山东枣庄277000

出　　处：《山东大学学报（医学版）》2012年第11期107-112,共6页Journal of Shandong University:Health Sciences

基　　金：山东省科技攻关项目(2008GG10002028);山东省自然科学基金(Y2005C65)

摘　　要：目的以聚乙二醇维生素E琥珀酸酯(TPGS)与豆磷脂(PC)为载体制备紫杉醇混合胶束,研究大鼠在体肠吸收及药物动力学行为。方法采用薄膜分散法制备紫杉醇混合胶束,采用激光散射粒度测定仪测定粒径、Zeta电位,采用透射电镜观察外观形态,采用动态膜透析法测定体外释放情况。运用大鼠在体单向肠灌流模型,考察载药胶束的肠吸收动力学。采用HPLC测定血药浓度,研究大鼠体内药物动力学。结果紫杉醇混合胶束的平均粒径为78.34 nm,Zeta电位为-7.84 mV,胶束多为球形。肠吸收实验中,紫杉醇混合胶束相比原料药口服液的吸收速率常数Ka增大,大鼠体内的达峰时间延长,血药浓度时间曲线下面积(AUC0-∞)明显增加(P<0.05)。结论 TPGS/PC混合胶束能够促进紫杉醇的口服吸收,提高口服生物利用度。Objective To prepare paclitaxel-loaded mixed micelles using D-α-tocopherol polyethylene glycol 1000 succinate（TPGS） and phosphatidylcholine（PC） and study the effect on oral absorption in rats.Methods Paclitaxel-loaded mixed micelles were prepared by the film dispersion method.Zeta potential and the diameter distribution of TPGS/PC mixed micelles were measured using the laser size scattering determinator.Morphology of micelles was observed by the transmission electron microscope.Dialysis method was used to evaluate the release behavior of drug-loaded micelles in vitro.The absorption kinetics was obtained by the in situ perfusion method in rats.Plasma paclitaxel concentration was determined by HPLC and the pharmacokinetics in rats was studied.Results Mixed micelles were almost spherical with an average diameter of 78.34 nm and the Zeta potential was-7.84 mV.Compared to the bulk drug,paclitaxel mixed micelles accelerated Ka,prolonged tmax and increased Cmax and AUC0-∞（P0.05）.Conclusion TPGS/PC mixed micelles can improve the oral absorption of paclitaxel,and increase its oral bioavailability.

关 键 词：紫杉醇 聚乙二醇维生素E琥珀酸酯 混合胶束 口服吸收 

分 类 号：R944.9[医药卫生—药剂学]