论文部分内容阅读
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。
Objective: In this study, K5-cholesterol polymer as a carrier of doxorubicin, its physical and chemical properties and cytotoxicity were evaluated. METHODS: Cholesterol was linked to K5 polysaccharide through amide bond to synthesize amphiphilic K5 polysaccharide-cholesterol polymer (KC). The drug-loaded micelles (DOX / KC) were prepared by self-assembly of doxorubicin (DOX) The particle size and zeta potential of DOX / KC were measured by dynamic light scattering. The encapsulation efficiency and drug loading were measured by ultrafiltration. The micelles were evaluated by dialysis in vitro. The cytotoxicity was evaluated by MTT assay. Bunch of cellular uptake. RESULTS: The mean particle size of DOX / KC prepared was (120.9 ± 2.7) nm, the value of electromotive force was - (25.7 ± 1.4) mV, the entrapment efficiency was (73.23 ± 0.88)% and the drug loading was ± 0.45)%, the results of transmission electron microscopy showed that the micelles were spherical and the particle size was more uniform. In vitro drug release studies have shown that the cumulative release rate of drugs at 48 h is close to 40%, with a significant sustained release effect. In vitro cytotoxicity experiments showed that, KC no obvious cytotoxicity to cells, showing good biocompatibility. DOX / KC has a significant inhibitory effect on MCF-7 human breast cancer cells in a concentration-dependent manner. Cell uptake results showed that DOX / KC enters cells in a time-dependent manner. Conclusion: The DOX / KC polymer micelles have the characteristics of sustained release and have the potential for clinical treatment of tumors.