Wang Yongzhong, Li Yajuan, Wang Qingsong, Wu Jiang, Fang Xiaoling
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, P.R. China.
Yakugaku Zasshi. 2008 Jun;128(6):941-50. doi: 10.1248/yakushi.128.941.
A mixed polymeric micelle formulation of paclitaxel (PTX) has been developed with the purpose of improving the solubility and prolonging the time of blood circulation of PTX in comparison to current Taxol injection. The mixed micelles were prepared by thin-film method using a nonionic surfactant Pluronic P105, L101 and PTX. The mean size of PTX-loaded mixed micelles was 185 nm with narrow size distribution shown by a dynamic light scattering sizer and a transmission electron microscopy. The in vitro release profiles indicated that PTX release from the mixed micelles exhibited a sustained release behavior. A similar phenomenon was also observed in a pharmacokinetic assessment in rats, in which t(1/2beta) and AUC of the mixed micelle formulation were 5.5 and 4.9-fold higher than that of Taxol injection. The biodistribution study in mice showed that the PTX-loaded mixed micelles not only decreased drug uptake by liver, but also prolonged drug retention in blood, and increased distribution of the drug in lung, spleen and kidney. These results suggested that the mixed polymeric micelles may efficiently load, protect and retain PTX in both in vitro and in vivo environments, and could be a useful drug carrier for intravenous administration of PTX.
已研发出一种紫杉醇（PTX）的混合聚合物胶束制剂，目的是与目前的紫杉醇注射液相比，提高PTX的溶解度并延长其在血液循环中的时间。使用非离子表面活性剂普朗尼克P105、L101和PTX，通过薄膜法制备混合胶束。载有PTX的混合胶束的平均尺寸为185纳米，动态光散射粒度仪和透射电子显微镜显示其尺寸分布狭窄。体外释放曲线表明，PTX从混合胶束中的释放呈现出缓释行为。在大鼠的药代动力学评估中也观察到了类似现象，其中混合胶束制剂的t(1/2β)和AUC分别比紫杉醇注射液高5.5倍和4.9倍。小鼠体内分布研究表明，载有PTX的混合胶束不仅减少了肝脏对药物的摄取，还延长了药物在血液中的保留时间，并增加了药物在肺、脾和肾中的分布。这些结果表明，混合聚合物胶束在体外和体内环境中都可以有效地负载、保护和保留PTX，并且可能是一种用于PTX静脉给药的有用药物载体。
