K5多糖-胆固醇聚合物胶束的制备及其表征

发布时间：2018-09-13 16:36

【摘要】：目的:本研究以K5-胆固醇聚合物为抗癌药物阿霉素的载体,对其理化性质和细胞毒性进行评价。方法:胆固醇通过酰胺键与K5多糖连接,合成两亲性K5多糖-胆固醇聚合物(KC),通过其自组装包载阿霉素(DOX)制得载药胶束(DOX/KC)。用动态光散射仪测定DOX/KC粒径和动电势,用超滤法测定包封率和载药量,用透析法评价胶束的体外释放,采用MTT法评价细胞毒性,用倒置显微镜观察胶束的细胞摄取情况。结果:所制备的DOX/KC的平均粒径为(120.9±2.7)nm,动电势值为-(25.7±1.4)m V,包封率为(73.23±0.88)%,载药量为(8.137±0.45)%,透射电镜观察结果表明,胶束呈球形且粒径较均匀。体外药物释放研究表明,48 h时药物的累计释放率接近40%,具有明显的缓释作用。体外细胞毒性实验表明,KC对细胞无明显细胞毒性,展现出良好的生物相容性。DOX/KC对MCF-7人乳腺癌细胞具有显著的抑制作用,且呈浓度依赖性。细胞摄取结果表明,DOX/KC进入细胞有时间依赖性。结论:DOX/KC聚合物胶束具有缓释的特点,有用于肿瘤临床治疗的潜能。
[Abstract]:Aim: to evaluate the physicochemical properties and cytotoxicity of K _ 5-cholesterol polymer as a carrier of adriamycin. Methods: the amphiphilic K5 polysaccharide-cholesterol polymer (KC), was synthesized by linking cholesterol with K5 polysaccharides via amide bond. The drug carrying micelles (DOX/KC) were prepared by self-assembly of doxorubicin (DOX). The particle size and electrokinetic potential of DOX/KC were measured by dynamic light scattering instrument, the encapsulation efficiency and drug load were measured by ultrafiltration method, the release of micelles in vitro was evaluated by dialysis method, the cytotoxicity was evaluated by MTT method, and the cellular uptake of micelles was observed by inverted microscope. Results: the average particle size of the prepared DOX/KC was (120.9 卤2.7) nm,. The electrokinetic potential value of the prepared DOX/KC was-(25.7 卤1.4) m V, entrapment efficiency was (73.23 卤0.88) and the drug loading was (8.137 卤0.45). The results of transmission electron microscopy showed that the micelles were spherical and uniform in size. In vitro drug release studies showed that the cumulative release rate was close to 40% at 48 h. In vitro cytotoxicity test showed that KC had no obvious cytotoxicity and showed good biocompatibility. Dox / KC had a significant inhibitory effect on MCF-7 human breast cancer cells in a dose-dependent manner. The results of cell uptake showed that DOX / KC entered the cells in a time dependent manner. Conclusion% DOX / KC polymer micelles have the characteristics of sustained release and potential for clinical treatment of cancer.
【作者单位】：江南大学药学院;
【基金】：国家自然科学基金资助项目(81503007)
【分类号】：R943

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