喜树碱/聚天冬氨酸衍生物-接枝-聚乙二醇共聚物胶束的制备及性质研究

The preparation and drug release of camptothecin/poly(aspartic acid) derivatives-graft-poly(ethylene glycol) copolymeric micelles

目的制备喜树碱/聚天冬氨酸衍生物-接枝-聚乙二醇的聚合物胶束,并对其化学结构进行表征。方法采用透析法制备喜树碱/聚合物胶束,采用动态激光散射法、透射电镜和核磁共振法测定胶束的粒径、形态及药物分布,采用高效液相色谱法测定喜树碱含量。结果喜树碱/聚合物胶束近似球形,粒径小于50nm,分布较窄,喜树碱被包裹在胶束内,在pH7.4的缓冲液中孵育12h,溶液组喜树碱70%被破坏,而被胶束组喜树碱仅有20%被破坏;在小鼠血浆中孵育12h,溶液组喜树碱90%多被破坏,而胶束组喜树碱约23%被破坏,喜树碱/聚合物胶束在pH7.4的介质中释药接近Higuchi模型。结论聚天冬氨酸衍生物-接枝-聚乙二醇聚合物胶束对喜树碱具有保护作用。

Objective To prepare a novel graft copolymeric micelle loading camptothecin and to explore its properties.Methods The polymeric micelle was prepared with dialysis method,the drug content was determined by HPLC.The size of micelle was monitored by dynamic static laser light scattering;the shape of micelle was observed by the transmission electron microscope.The drug distribution in micelle-core was confirmed by 1HNMR.Results The polymeric micelles loading CPT showed almost spherical shapes with core/shell structure and their size was less than 50 nm with narrow distribution.Free CPT was destroyed more than 70%,while CPT loaded by micelle was destroyed less than 20% in pH 7.4 PBS for 12 h.Free CPT was destroyed more than 90%,while CPT loaded by micelle was destroyed about 23% in plasma for 12 h.Conclusion The poly（aspartic acid） derivatives-graft-poly（ethylene glycol） polymeric micelles can protect the instable drug under biological surroundings.