转运紫杉醇的PLGA纳米粒对膀胱癌的细胞毒作用

摘要

目的 研究可转运紫杉醇的多聚体纳米粒对膀胱癌的细胞毒作用. 方法 应用微乳化方法制备载紫杉醇的聚乳酸-羟基乙酸共聚物(PLGA)纳米粒,以聚乙烯醇(PVA)为表面稳定剂,并以转铁蛋白(Tf)表面修饰,分析纳米粒的大小、表面电荷、载药浓度、药物释放曲线以及空白纳米粒的安全性,观察紫杉醇溶液及载紫杉醇纳米粒对膀胱癌细胞系J-82的细胞毒作用. 结果 PVA纳米粒直径约200 nm,Z电势约-24 mV,载药浓度约6.5％ (w/w),药物释放曲线为双相性.Tf表面修饰的纳米粒直径比PVA纳米粒稍大,Z电势、载药浓度、药物释放曲线与PVA纳米粒相似.两种空白纳米粒不具有细胞毒性.紫杉醇溶液在50 ng/ml时J-82细胞存活率为82.0％,100 ng/ml时为36.0％.PVA纳米粒在50 ng/ml和100 ng/ml时细胞存活率分别为40.2％和15.8％,而Tf纳米粒分别为32.9％和7.2％,两种载药纳米粒抑制J-82细胞的作用明显强于紫杉醇溶液. 结论 PLGA纳米粒是安全有效的载药工具,可以明显增强紫杉醇对膀胱癌的细胞毒作用.%Objective To formulate paclitaxel loaded polymer nanoparticle and evaluate it's application in treatment of bladder.Methods Paclitaxel loaded Poly (lactide-co-glycolide) (PLGA) nanoparticles were formulated with microemulsion method,Polyvinyl alcohol(PVA) was used as surfactant.Transferrin (Tf) was used to modify the nanoparticles.The size,Z-potential,drug loading,drug release,cytotoxicity of bland nanoparticles and paclitaxel-loaded nanoparticles on bladder cancer cell line J-82 were measured.Results The size of nanoparticles was about 200 nm,Z-potential was-24 mV,drug loading was about 6.5％ (w/w),cumulative drug release showed two phase curve.The size of Tf modified nanoparticles was a little bigger than no modified nanoparticles.The Z-potential,drug loading,drug release was similar.Two kinds of blank nanoparticles showed no cytotoxicity on bladder cancer cell line J-82.However,both paclitaxel-loaded nanoparticles had significantly higher cytotoxicity on J-82 compared to paclitaxel solution.Conclusions PLGA nanoparticle is a promising drug delivery vehicle,which could significantly improve the anticancer effect of paclitaxel on bladder cancer.