K5多糖-胆固醇聚合物胶束的制备及其表征  

Preparation and characterization of K5 polysaccharide-cholesterol polymeric micelles

作　　者：赵丽 邱立朋 朱梦琴 葛璐 陈敬华 

机构地区：[1]江南大学药学院,无锡214122

出　　处：《中国新药杂志》2017年第16期1961-1967,共7页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(81503007)

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。Objective： To prepare doxorubicin polymeric micelles using K5 polysaccharide-cholesterol （KC） as the carrier and study the properties of the mieelles. Methods： K5 polysaccharide was conjugated with cholesterol via acid amides bond to obtain K5-cholesterol （KC） , which was characterized by I H NMR. Doxorubicin- loaded micelles （DOX/KC） were prepared and the morphology of the mieelles were observed by transmission electron microscope （TEM） , the size and the zeta potential of micelles were measured by using dynamic light scattering （DLS）. The encapsulation efficiency and drug loading were measured by ultrafihration and the release behavior was studied by dialysis method. The cytotoxicity was evaluated by MTT assay and the cell uptake was observed by fluorescence microscope. Results：The particle size and ζ potential of DOX/KC were （120.9±2.7） nm and - （25.7 ± 1.4） mV, respectively. The encapsulation efficiency and drug loading were （73.23 ±0.88） % and （8. 137 ± 0.45）% , respectively. The TEM observation showed that the micelles had uniform spherical structure. In vitro drug release study showed that the accumulative drug release rate reached nearly 40% within 48 h, indicating obvious sustained release effect. The In vitro cytotoxicity and cellular uptake were evaluated against MCF-7 cells. The results showed that KC micelles had no obvious toxicity. DOX/KC had obvious inhibitory effect in a dose- dependent manner. DOX/KC entered cells in a time-dependent manner. Conclusion： DOX/KC with sustained release property may have a promising potential for targeting cancer therapy in clinic.

关 键 词：K5多糖 阿霉素 聚合物胶束 抗肿瘤活性 

分 类 号：R944.9[医药卫生—药剂学]