pH-响应型K5多糖药物传递系统的构建及应用

化学疗法是目前癌症治疗的主要方法，但目前常用的化疗药物却普遍存在水溶性不佳、缺乏选择性、毒副作用大等不足，而限制了其应用。本研究基于肝素前体K5多糖为模板，利用具有pH响应性的硼酸酯键，构建了K5-脱氧胆酸（K5AD）两亲性药物传递系统，用于阿霉素（doxorubicin，DOX）的靶向传递释放。考察了该体系的体外药物释放行为，并在体外评价其对肿瘤细胞的抑制作用。结果表明，K5AD的临界胶束浓度值为23.5mg/L，在水溶液中能自组装形成平均粒径为196.7nm的胶束；K5AD-DOX体外药物释放实验显示其具有pH-响应的释药行为，在pH 5.0的酸性环境下药物释放速率较pH 7.4下更快。细胞实验表明，K5AD-DOX对肿瘤细胞的毒性远大于对正常细胞的毒性，表现出治疗的选择性。

Construction and application of novel pH responsive drug delivery system based on K5 polysaccharide

Chemotherapy is the one of the main methods used for cancer therapy.However,current chemotherapeutics exhibit poor water solubility,low selectivity and strong side-effects,while limiting their applications.In this study,we used the precursor of heparin,K5 polysaccharide,as the building block,which conjugated with deoxycholic acid via boronate ester bond,to construct a novel amphiphilic drug delivery system for the transportation of doxorubicin(DOX).The in vitro drug release behavior and anticancer efficacy of K5AD were evaluated.The results showed that the critical micelle concentration(CMC) of K5AD micelles was 23.5mg/L,and their average particle size was 196.7 nm.In vitro drug release assay indicated the variation of pH value could adjust drug release rate,which was faster at acidic milieu(pH 5.0) than at pH 7.4.The cytotoxicity assay showed that K5AD-DOX could significantly inhibit the proliferation of cancer cells rather than normal cells,showing favorable selectivity during the treatment.