双还原敏感的混合胶束用作为抗肿瘤药物的载体

通过酯化缩聚制备了含双硒键的聚合物聚乙二醇-缩-二硒二(十一酸)(PEG-SeSe-PEG),用核磁和红外确证了其结构。临界胶束浓度(CMC)结果表明,PEG-SeSe-PEG与两亲聚合物聚己内酯-二硫键-b-聚甲基丙烯酸二乙胺基乙酯/聚磺酸甜菜碱(PCL-SS-PDEA-PS)一样能够形成胶束,并且两者能形成混合胶束。用动态光散射和扫描电镜对胶束的粒径和还原敏感进行了研究。粒径变化显示混合胶束有双还原敏感性。用紫外分光光度计测定了胶束对疏水性抗癌药物模型姜黄素的载药量(DLC)和包封率(DLE)。PCL-SS-PDEA-PS占80%的双还原敏感胶束(混合胶束E)的载药量和包封率最高。体外释药结果显示,双还原敏感胶束在还原环境中的释药速率快于非还原环境。体外细胞毒性结果表明,双还原敏感胶束比PCL-SS-PDEA-PS胶束的细胞相容性好,而且载药E胶束能最好地抑制Hela细胞生长。

Dual Reduction-Sensitive Mixed Micelles as the Carries for Antineoplastic Drugs

A copolymer containing diselenium was synthesized by esterification polycondensation of poly(ethylene glycol) and 11,11'-diselenium-bi-decanoic acid (PEG-SeSe-PEG).The structure of PEG-SeSe-PEG was confirmed by 1H-NMR and FT-IR.The results of critical micdle concentration (CMC) indicate that the micelles of PEG-SeSe-PEG could be formed by the individual copolymer or together with an amphiphilic copolymer poly(ε-caprolactone)-SS-poly (N,N-diethylaminoethylmethacrylate)-r-poly (N-(3-sulfopropyl)-N-methacryloxyethy-N,N-diethylammoniumbetaine) (PCL-SS-PDEA-PS).The mixed micelles contain two kinds reduction-sensitive copolymers.Dynamic light scattering (DLS) and scanning electron microscopy (SEM) were performed to determine the micelle size,Zeta potential and reduction-sensitive of the micelles/mixed micelles.The change of the micelle sizes of the mixed micelles displays dual reduction-sensitivity for the mixed micelles.Drug loading content (DLC) and drug loading efficiency (DLE) were determined by UV-visible absorbance.The results indicate that the mixed micelle E (80 ％ PCL-SS-PDEA-PS) has the maximum DLC and DLE.The profiles of in vitro drug release of the drug-loaded micelles show that mixed micelles are faster in reduction environment than in absence of reductant.In vitro cytotoxicity of the mixed micelle is lower than that of the micelles individually formed by PCL-SS-PDEA-PS,and the mixed micelle E shows the best effect to kill Hela cell.