【作者】 刘瑶； 霍美蓉； 周建平；

【Author】 LIU Yao,HUO Mei-rong,ZHOU Jian-ping(State Key Laboratory of Natural Medicines,Department of Pharmaceutics,China Pharmaceutical University,Nanjing 210009,China

【机构】 中国药科大学天然药物活性组分与药效国家重点实验室；

【摘要】 目的以非还原敏感壳聚糖胶束(HECS-OA)胶束为对照,考察还原敏感壳聚糖(HECS-ss-OA)胶束负载药物能力、理化性质及体内药效学行为。方法采用透析法制备载紫杉醇(PTX)胶束PTX-HECS-ss-OA及PTX-HECS-OA,并测定其载药量、包封率、形态、粒径,考察载体和载药胶束的体外溶血行为,并评价载药胶束在S180荷瘤ICR小鼠体内的药效学行为。结果 PTX-HECS-OA和PTX-HECS-ss-OA载药量分别为31.4%和31.2%,包封率为82.5%和81.5%,粒径为141.1nm和167.6nm,原子力显微镜(AFM)图片显示载药胶束为类球状结构,粒径分布均匀,体外溶血试验显示HECS-OA、HECS-ss-OA偶联物及其载药胶束相对于市售制剂Taxol具有更好的溶血安全性。体内药效学实验结果表明PTX-HECS-ss-OA胶束组较市售制剂Taxol组和PTX-HECS-OA胶束组具有更显著的抑瘤效果及更低的系统毒性。结论 HECS-ss-OA可成为胞内触发式给药的优良新型的药物载体,具有良好的应用前景。更多还原

【Abstract】 OBJECTIVE To evaluate the drug loading capacity,physicochemical properties and pharmacodynamics of redox sensitive chitosan micelles (HECS-ss-OA) using non-redox sensitive chitosan micelles (HECS-OA) as control.METHODS The paclitaxel (PTX) loaded chitosan micelles was prepared by dialysis and was characterized by drug loading content,entrapment efficiency,morphology and particle size.The in vitro hemolysis of blank micelles and drug-loaded micelles was tested and compared to the Taxol .The in vivo anti-tumor effect of PTX-HECS-ss-OA micelles was evaluated on BALB/C mice bearing S180 tumor using Taxol and PTX-HECS-OA as controls.RESULTS PTX loaded HECS-OA micelles and HECS-ss-OA micelles were prepared with loading content of 31.4% and 31.2%,entrapment efficiency of 82.5% and 81.5%,respectively.The AFM images of PTX-HECS-ss-OA micelles showed a spherical shape.HECS-ss-OA and HECS-ss-OA micelles loaded with PTX exhibited less hemolysis compared to Taxol.PTX-loaded HECS-ss-OA micelle exhibited the strongest anti-tumor activity compared with PTX-loaded HECS-OA micelle and Taxol with the lowest systemic toxicityt.Conclusion These results suggest that redox-sensitive HECS-ss-OA micelles hold great potential as targeted intracellular delivery carriers of lipophilic anti-cancer drugs.更多还原