Han Li-Mei, Guo Jie, Zhang Li-Jun, Wang Qing-Song, Fang Xiao-Ling
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China.
Acta Pharmacol Sin. 2006 Jun;27(6):747-53. doi: 10.1111/j.1745-7254.2006.00340.x.
To investigate the preparation, in vitro release, in vivo pharmacokinetics and tissue distribution of a novel polymeric micellar formulation of paclitaxel (PTX) with Pluronic P123.
The polymeric micelles of paclitaxel with Pluronic P123 were prepared by a solid dispersion method. The characteristics of micelles including particle size distribution, morphology and in vitro release of PTX from micelles were carried out. PTX-loaded micellar solutions were administered through the tail vein to healthy Sprague-Dawley rats and Kunming strain mice to assess the pharmacokinetics and tissue distribution of PTX, respectively. Taxol, the commercially available intravenous formulation of PTX, was also administered as control.
By using a dynamic light scattering sizer and a transmission electron microscopy, it was shown that the PTX-loaded micelles had a mean size of approximately 25 nm with narrow size distribution and a spherical shape. PTX was continuously released from Pluronic P123 micelles in release medium containing 1 mol/L sodium salicylate for 24 h at 37 centigrade degree. In the pharmacokinetic assessment, t(1/2beta) and AUC of micelle formulation were 2.3 and 2.9-fold higher than that of Taxol injection. And the PTX-loaded micelles increased the uptake of PTX in the plasma, ovary and uterus, lung, and kidney, but decreased uptake in the liver and brain in the biodistribution study.
Polymeric micelles using Pluronic P123 can effectively solubilize PTX, prolong blood circulation time and modify the biodistribution of PTX.
研究一种新型的紫杉醇（PTX）与普朗尼克P123聚合物胶束制剂的制备、体外释放、体内药代动力学及组织分布。
采用固体分散法制备紫杉醇与普朗尼克P123的聚合物胶束。对胶束的特性进行研究，包括粒径分布、形态以及紫杉醇从胶束中的体外释放。将载有紫杉醇的胶束溶液经尾静脉分别注射到健康的斯普拉格-道利大鼠和昆明种小鼠体内，以评估紫杉醇的药代动力学和组织分布。市售的紫杉醇静脉制剂泰素也作为对照给药。
通过动态光散射粒度分析仪和透射电子显微镜显示，载紫杉醇胶束的平均粒径约为25nm，粒径分布窄且呈球形。在含有1mol/L水杨酸钠的释放介质中，37℃条件下，紫杉醇从普朗尼克P123胶束中持续释放24小时。在药代动力学评估中，胶束制剂的t(1/2β)和AUC分别比泰素注射液高2.3倍和2.9倍。在生物分布研究中，载紫杉醇胶束增加了紫杉醇在血浆、卵巢、子宫、肺和肾脏中的摄取，但降低了在肝脏和大脑中的摄取。
使用普朗尼克P123的聚合物胶束可有效增溶紫杉醇，延长血液循环时间并改变紫杉醇的生物分布。
