还原敏感型壳聚糖胶束作为紫杉醇肿瘤递药载体地研究.pdfVIP

还原敏感型壳聚糖胶束作为紫杉醇肿瘤递药载体的研究 * * 刘瑶 霍美蓉 周建平 （中国药科大学天然药物活性组分与药效国家重点实验室，南京 210009 ） 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 141.1 nm 和 167.6 nm，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。 关键词：还原敏感型；壳聚糖；胶束；谷胱甘肽 Redox-sensitive chitosan micelles using as tumor delivery carrier for paclitaxel State Key Laboratory of Natural Medicines, Department of LIU Yao, HUO Mei-rong*, ZHOU Jian-ping* （ Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China 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