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目的制备紫杉醇囊泡,对其进行表征,进一步研究其在大鼠体内的药动学特征及组织分布情况。方法以司盘(Span)和胆固醇(CH)为主要膜材,用薄膜分散法制备紫杉醇囊泡,采用正交实验进行处方优化,用透射电镜考察其形态和构造,用激光粒度仪测定囊泡的粒径大小和ζ电位,按7.5,15,30mg·kg-13个剂量大鼠颈静脉给药后检测一定时间点的血药浓度,对照为15mg·kg-1的紫杉醇注射液。结果紫杉醇囊泡的平均粒径为(157±16)nm,冻干后紫杉醇囊泡的平均粒径为(189±23)nm;冻干后的紫杉醇囊泡在贮存6个月的时间内包封率没有明显变化,粒径略有增大。紫杉醇囊泡相对于紫杉醇注射液体内半衰期显著延长,生物利用度提高;组织分布结果显示明显的肝脾靶向性。结论成功研制了紫杉醇囊泡,囊泡有望成为紫杉醇新的剂型。
Objective To prepare paclitaxel vesicles, characterize them and further study their pharmacokinetics and tissue distribution in rats. Methods Paclitaxel vesicles were prepared by thin film dispersion method using Span and Cholesterol (CH) as main materials. The orthogonal experiment was used to optimize the formulation. The morphology and structure of paclitaxel vesicles were investigated by transmission electron microscopy. The particle size and zeta potential were measured at 7.5, 15 and 30 mg · kg-13 doses of jugular vein, and the control group was given paclitaxel at a dose of 15 mg · kg-1. Results The mean particle size of paclitaxel vesicles was (157 ± 16) nm. The mean particle size of paclitaxel vesicles after lyophilization was (189 ± 23) nm. Paclitaxel vesicles after lyophilization were encapsulated within 6 months Rate did not change significantly, the particle size increased slightly. Paclitaxel vesicles relative paclitaxel injection significantly prolonged half-life, bioavailability increased; tissue distribution showed significant liver-spleen targeting. Conclusions Paclitaxel vesicles have been successfully developed and the vesicles are expected to become the new dosage form of paclitaxel.