紫杉醇温敏原位水凝胶的制备及抗肿瘤活性  

Preparation and anti-tumor activity of paclitaxel thermo-sensitive hydrogel

作　　者：孙娟[1] 鞠曹云[1] 张灿[1] 

机构地区：[1]中国药科大学新药研究中心,南京210009

出　　处：《中国药科大学学报》2012年第5期424-429,共6页Journal of China Pharmaceutical University

基　　金：教育部博士点基金资助项目(No.20090096110005);江苏省研究生培养创新工程资助项目(No.CXZZ11-0806)~~

摘　　要：制备紫杉醇胶束水凝胶复合制剂(PTX-M-P407),考察该体系的体外释放以及在异位荷鼠源肝实质瘤小鼠体内的组织分布以及抗肿瘤活性。采用冷法制备紫杉醇胶束水凝胶;无膜溶出法考察药物的释放行为;通过异位荷瘤小鼠瘤内注射紫杉醇市售制剂Taxol、紫杉醇胶束(PTX-M)和PTX-M-P407,比较3种制剂的组织分布特征以及体内抗肿瘤活性。药物的体外释放由水凝胶的溶蚀决定,并呈现零级动力学特征。瘤内给药后的体内实验结果表明:Taxol、PTX-M和PTX-M-P407在肿瘤组织的AUC分别为77.43,127.53和935.75 d.μg/g,MRT分别0.76,0.65和6.92 d,并且PTX-M-P407对鼠源肝实体瘤生长具有较好的抑制作用,说明PTX-M-P407的瘤内转运是实体瘤治疗的有效手段。This study was to prepare a novel injectable thermosensitive hydrogel system incorporating paclitaxel loaded micelle（PTX-M-P407）,and to assess the in vitro drug release profile,tissue distribution and anti-tumor efficacy in Heps tumor-bearing mice.PTX-M-P407 was prepared with cold method.Drug release profile was evaluated with membranes-less method.Tissue distribution and in vivo anti-tumor activity were compared after intratumoral injection of Taxol,PTX-M and PTX-M-P407 in Heps tumor-bearing mice.In vitro drug release was in accordance with Zero order kinetics which was determined by hydrogel dissolution.After intratumoral injection of Taxol,PTX-M and PTX-M-P407,AUCs in tumor were 77.43,127.53 and 935.75 d ·μg/g,and MRTs were 0.76,0.65 and 6.92 d,respectively.In vivo anti-tumor study demonstrated that PTX-M-P407 was superior in impeding tumor growth than other PTX formulations.In conclusion,PTX-M-P407 was a promising intratumoral drug delivery system to enhance anti-tumor efficacy.

关 键 词：紫杉醇 胶束 泊洛沙姆407 瘤内注射 抗肿瘤活性 

分 类 号：R943[医药卫生—药剂学] R96[医药卫生—药学]