还原响应型K5多糖胶束药物载体的研究

Preparation and Properties of the Redox-Sensitive K5Polysaccharide Micelles as Drug Carrier

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K5PSSS-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225nm与-31mV,载药后为241nm与-31mV,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。

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-31mV for the micelles,and 241nm and-31mV for the DOX-loaded micelles,showing favorable stability. The DOX-loaded micelles could behave redox-sensitive drug release behavior in the solution containing 10m M 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.