紫杉醇聚合物胶束的组织分布和生物学评价  

Biodistribution and biological evaluation of paclitaxel polymer micelles

作　　者：姚天怡 尹少平 刘雯 赵炎磊 王广基[2] 李娟 YAO Tianyi;YIN Shaoping;LIU Wen;ZHAO Yanlei;WANG Guangji;LI Juan(Department of Pharmaeeutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, Jiangsu, China;Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Naajing 210009, Jiangsu, China)

机构地区：[1]中国药科大学药学院药剂系 [2]中国药科大学药物代谢动力学重点实验室

出　　处：《中国临床药理学与治疗学》2017年第11期1207-1214,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金面上项目(81373363);国家科技部十一五重大新药创制(2009ZX09310-004);江苏省科技支撑-社会发展项目(BE2010723);江苏省研究生创新工程(CXLX11-0813)

摘　　要：目的:研究紫杉醇(paclitaxel,PTX)聚合物胶束的荷瘤鼠组织分布和生物安全性。方法:采用S180荷瘤小鼠模型研究静脉注射PTX聚合物胶束和Taxol的药动学参数变化、组织分布特征和抗肿瘤作用;通过动物实验研究PTX聚合物胶束的急性毒性、溶血性和静脉刺激性。结果:PTX聚合物胶束的t1/2和平均滞留时间(MRT)分别为Taxol的3.52和4.55倍,在肿瘤部位的相对摄取率为2.31,表明该胶束具有长循环和肿瘤靶向作用。PTX聚合物胶束对S180荷瘤小鼠的抑制显著强于Taxol(P<0.05)。生物安全性评价结果显示PTX聚合物胶束的最大耐受剂量和LD50均显著高于Taxol(P<0.05),对兔耳缘静脉无明显血管刺激性。结论:PTX聚合物胶束延长了药物体内循环时间、增强了肿瘤靶向性和抗癌活性,提高了生物安全性,期望为临床提供一种高效、低毒紫杉醇聚合物胶束靶向制剂。AIM：The biodistribution in tumorbearing mice and biosafety of paclitaxel （FTX） polymer micelles were investigated.METHODS：The pharmacokinetic study,tissue distribution and antineoplastic effect of PTX polymer micelles and Taxol were evaluated on S180 tumor-bearing mice after intravenous injection.Animals were used to research the acute toxicity,hemolysis and venous irritation of PTX polymer micelle.RESULTS：The t1/2 and MRT of PTX polymer micelles were 3.52 and 4.55 times of Taxol,respectively.Tissue distribution studies showed that the relative uptake rate of PTX polymer micelles at tumor sites was 2.31.The results indicated that PTX polymer micelles improved the circulation time and tumor targeting.The antitumor efficacy of PTX polymer micelles was significantly higher than Taxol.Maximum tolerated dose and LD50 of PTX polymer micelles were significantly improved.PTX polymer micelles had no obvious vascular irritation to ear vein of rabbits.CONCLUSION：The circulation time,tumor targeting,antineoplastic effect and biosafety of FTX polymer micelles were improved,which might turn into a promising tumor targeting paclitaxel polymer micelle preparations in clinic with maximum effect and minmum toxicity.

关 键 词：紫杉醇 聚合物胶束 组织分布 抗肿瘤活性 安全性评价 

分 类 号：R965.2[医药卫生—药理学]