紫杉醇混合胶束的制备及其大鼠在体肠吸收  

Preparation of Paclitaxel-loaded Mixed Micelles and its in situ Absorption in Rat Intestine

作　　者：李一木[1] 赵艳丽[1] 李凌冰[1] 

机构地区：[1]山东大学药学院药剂教研室,济南250012

出　　处：《中国药学杂志》2013年第13期1076-1082,共7页Chinese Pharmaceutical Journal

基　　金：山东省科技攻关项目(2008GG10002028);山东大学国家级大学生科技创新计划(201310422089)

摘　　要：目的以聚乙二醇维生素E琥珀酸酯与胆酸钠为载体制备紫杉醇混合胶束,并研究其在大鼠小肠各部位的吸收情况。方法 采用薄膜分散法制备紫杉醇混合胶束,激光散射粒度测定仪测定粒径、Zeta电位,用透射电镜观察外观形态,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。结果 紫杉醇混合胶束的平均粒径为24.2 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度常数(Ka)明显增大。结论 TPGS/NaC混合胶束能够促进紫杉醇的口服吸收,有可能会提高口服生物利用度。Objective To study the oral absorption of paclitaxel-loaded mixed micelles made of D-α-tocopherol polyethylene glycol 1000 succinate（TPGS） and sodium cholate（NaC） in rats. Methods Paclitaxel-loaded mixed micelles were prepared by film dispersion method. The Zeta potential and diameter distribution of TPGS/NaC mixed micelles were measured using laser size scattering determinator. The morphology of micelles was observed by transmission electron microscope. Dialysis method was used to evaluate the release behavior of drug-loaded micelles in vitro. The absorption kinetics was obtained by in situ perfusion method in rats. Results Most of the mixed micelles were spherical with an average diameter of 24.2 nm and the Zeta potential was -7.84 mV. Compared to the bulk drug, the apparent absorption rate constant （Ka）of paclitaxel-loaded mixed micelles was increased significantly.Conclusion TPGS/NaC 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 胆酸钠 混合胶束 口服吸收 

分 类 号：R944[医药卫生—药剂学]