还原响应型K5多糖胶束药物载体的研究

Preparation and Properties of the Redox-Sensitive K5 Polysaccharide Micelles as Drug Carrier

摘要:

为了解决传统抗肿瘤药物阿霉素水溶性不佳，对机体选择性差的情况，设计了一种还原敏感的K5胶束药物载体。将脱氧胆酸（DOCA）通过双硫键与K5多糖连接，制备两亲性K5PS-SS-DOCA（KSD）缀合物。该缀合物在水溶液中可自组装形成胶束并包载模型药物阿霉素（DOX）。胶束形貌通过透射电镜进行观测，并进一步通过动态光散射测定其水合粒径及ζ-电位。胶束为球形，其水合粒径和ζ电位在载药前分别为225 nm与-31 mV，载药后为241 nm与-31 mV，具有较好的稳定性。该胶束在谷胱甘肽（GSH）存在条件下，可表现出明显的还原响应药物释放行为。细胞实验结果证实，载体材料有良好的生物相容性，含药胶束对肿瘤细胞的半数抑制浓度（IC50）低于正常细胞，对肿瘤细胞有明显选择性。

Abstract:

To overcome the poor water solubility or lack of tumor-targeting of Doxorubicin（DOX）, we designed and fabricate the redox-sensitive K5 polysaccharide micelles as drug carrier, methods：An amphiphilic K5PS-SS-DOCA（KSD） conjugate was designed and prepared by covalently coupling deoxycholic acid（DOCA） with K5 polysaccharide（K5PS） via disulfide bonds. The conjugate could self-assemble into micelles in aqueous solution and encaspulate model drug DOX. The morphology of the micelles was observed by TEM, and the size and ζ-potential were measured by DLS. Results：The micelles were of spherical shape. The average size and ζ-potential was 225 nm and -31 mV for the micelles, and 241 nm and -31 mV for the DOX-loaded micelles, showing favorable stability. The DOX-loaded micelles could behave redox-sensitive drug release behavior in the solution containing 10 mM GSH. In vitro cytotoxicity showed that the bare micelles were biocompatible and DOX-loaded KSD micelles were more cytotoxic against tumor cells than normal cells.