载姜黄素的胆固醇-透明质酸聚合物胶束的制备及评价  

Preparation and Evaluation of Curcumin-loaded Polymeric Micelles Based on Copolymer Cholesterol-hyaluronic Acid

作　　者：刘雅茹 吴孟霏 孙玉琦 LIU Yaru;WU Mengfei;SUN Yuqi(Jinzhou Medical University,Jinzhou 121001)

机构地区：[1]锦州医科大学,辽宁锦州121001

出　　处：《中国医药工业杂志》2020年第5期613-619,共7页Chinese Journal of Pharmaceuticals

基　　金：辽宁省自然科学基金资助项目(201602312)。

摘　　要：通过化学交联法将胆固醇(Chol)与透明质酸(HA)连接,合成两亲性胆固醇-透明质酸聚合物(CH-HA),用薄膜分散-超声法制得载抗肿瘤药姜黄素的聚合物胶束。动态光散射(DLS)和透射电镜(TEM)的表征结果显示,载药胶束的粒径为(148.9±3.1)nm,ζ电位为(-29.7±2.4)mV,外观呈球形且粒度分布较均匀。本品包封率为(79.58±0.36)%,载药量为(7.57±0.36)%,在pH 7.4磷酸盐缓冲液中10和48 h时累积释放率约为45%和55%,提示其具有一定的缓释性能。初步稳定性考察结果显示,本品在4℃放置30 d,粒径略增大但包封率明显下降。体外细胞毒性试验表明,空白胶束对肿瘤细胞A549及正常细胞L929均无明显细胞毒性,展现出良好的生物相容性;而载药胶束对A549细胞具有浓度依赖性的抑制作用,但对L929细胞的毒性较小。细胞摄取试验显示,A549细胞对载药胶束的摄取率明显高于L929细胞,并且肿瘤细胞的相对摄取率随时间延长而显著降低。The amphiphilic copolymer cholesterol-hyaluronic acid(CH-HA) was synthesized with cholesterol(Chol) and hyaluronic acid(HA) by chemical cross-linking, then the curcumin-loaded micelles based on the obtained copolymer were prepared by ultrasonic dispersion method. The particle size and ζ potential of the curcuminloaded micelles determined by dynamic light scanning(DLS) were(148.9±3.1)nm and(-29.7±2.4)mV, respectively. The observation of transmission electron microscopy(TEM) showed that the micelles were quasi-circular and distribution uniformity. After ultrafiltration, the encapsulation efficiency and drug loading were determined as(79.58±0.36)% and(7.57±0.36)%, respectively. In vitro release test showed that the cumulative release amounts at 10 and 48 h were 45%and 55% in pH 7.4 phosphate buffer, indicating a certain sustained-release performance. The preliminary stability results showed that the particle size of micelles stored at 4 ℃ for 30 d slightly increased but the encapsulation efficiency significantly decreased. In vitro cytotoxicities of the blank and drug-loaded micelles were determined by MTT assay on A549 human lung cancer cells and L929 fibroblast cells. The results demonstrated that the blank micelles had no significant cytotoxicity against A549 cells and L929 cells, showing the CH-HA copolymer had good biocompatibility. The curcumin-loaded micelles displayed a concentration-dependent inhibition effect on the growth of A549 cells, but rather weak cytotoxicity against L929 cells. The cell uptake experiment showed that the uptake of curcumin-loaded micelles in A549 cells was significantly higher than that in L929 cells, and the relative uptake of polymer micelles in A549 cells decreased in a time-dependent manner.

关 键 词：姜黄素 胆固醇-透明质酸聚合物 聚合物胶束 细胞毒性 抗肿瘤活性 

分 类 号：R944.9[医药卫生—药剂学]