紫杉醇囊泡的研制及大鼠体内的药动学特征  

Preparation and Pharmacokinetics of Paclitaxel Niosomes

作　　者：朱铉[1] 扶艳[1] 苏美琴[1] 阮航[1] 张真[1] 梁信芳[1] 

机构地区：[1]厦门大学医学院药学系,福建厦门361005

出　　处：《中国药学杂志》2010年第5期365-371,共7页Chinese Pharmaceutical Journal

基　　金：福建省自然科学基金资助项目(2008J0115);福建省新世纪优秀人才计划资助

摘　　要：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 and characterize the paclitaxel niosomes,and to study the pharmacokinetics and tissue distribution in rats.METHODS The paclitaxel niosomes were prepared with Span and cholesterol using thin-film hydration method.The vesicles were visualized by transmission electron microscopy and sized by laser particle analyzer on a Malvern Mastersizer.The prescription was optimized by using orthogonal design.The pharmacokinetic parameters of paclitaxel were determined in rats after intravenous paclitaxel noisomes（7.5,15,30 mg·kg^-1）and intravenous Taxol（15 mg·kg^-1）to rats.RESULTS The given niosomes were the suspension finely dispersed in aqueous solution.The mean size of the vesicles was 157 nm.After freeze-drying,the mean size of the vesicles was 189 nm.There was no significant change in encapsulation efficiency for six months.The niosomes significantly increased the biological half-life of paclitaxel after intravenous injection in rats.The tissue distribution showed high accumulation of the drug in liver and spleen tissues.CONCLUSION Paclitaxel noisomes may be considered as an effective anticancer drug delivery system for cancer chemotherapy.

关 键 词：囊泡 包封率 紫杉醇 药动学 组织分布 

分 类 号：R944[医药卫生—药剂学]