【摘要】 以难溶性抗肿瘤药物紫杉醇(PTX)为模型,自制的新型两亲性壳聚糖衍生物N-辛基-N’-(2-羧基环己甲酰基)-壳聚糖(OCCC)为载体,用透析法制备了紫杉醇聚合物胶束(PTX-M),对其载药工艺进行优化并评价了PTX-M胶束的大鼠体内药动学,小鼠体内组织分布,小鼠抗肿瘤药效学以及小鼠体内近红外活体成像。结果表明PTX-M具有高载药量(43.25%),Vc和t1/2β分别提高了11.4和2.83倍,但是AUC为对照Taxol的1/3,这与胶束在体内的快速分布有关。小鼠体内组织分布研究表明:与参比Taxol相比,胶束全血分布结果与药动学一致,静注后会快速向各组织广泛分布,其中肝、脾、肺分布减少。抗肿瘤药效学研究表明:与参比Taxol相比,PTX-M具有更好的抗肿瘤活性且无明显毒副作用。更多还原

【Abstract】 A water-insoluble antitumor agent,paclitaxel(PTX) was successfully incorporated into polymeric micelles formed from new graft copolymers,N-octyl-N-(2-carboxyl-cyclohexamethenyl) chitosan derivatives(OCCC).The objective of this study was to optimize and characterize the novel PTX micelle(PTX-M).Furthermore,the pharmacokinetics,NIR-imaging,biodistribution,and anti-tumor effects of PTX-M were evaluated.The results showed that the PTX-M has high drug loading(43.25%).TheVdandt1/2βof PTX-M were increased by 11.4 and 2.83-fold,respectively,but the plasma AUC of PTX-M was 3.8-fold lower than that of Taxol.Biodistribution study indicated that PTX-M was widely distributed into most tissue,whish was found in liver,spleen,lung and kidney.Tumor growth was significantly inhibited after intravenous injection of PTX-M.PTX-M showed the enhanced anti-tumor effect and non-toxic effects compared with Taxol,the commercial product of PTX.Therefore,chitosan derived micelle system offered a stable and effective platform for cancer chemotherapy with PTX.更多还原