透明质酸-甘氨酸-喜树碱聚合物胶束的制备及其体外抗肿瘤活性研究
Preparation and in vitro anti-tumor activity of hyaluronic acid-glycine-camptothecin polymer micelles
宋帅恒 1杜昊洋 1磨莲清 1陈续含 1包乌日罕 1林锋1
作者信息
- 1. 哈尔滨医科大学药学院有机化学教研室,哈尔滨 150081
- 折叠
摘要
目的 合成透明质酸-甘氨酸-喜树碱聚合物胶束(HA-Gly-CPT胶束),并且评价该胶束的质量,初步研究其体外抗肿瘤活性.方法 利用甘氨酸将透明质酸与喜树碱连接,形成两亲性聚合物;通过红外光谱法、核磁共振氢谱法表征其结构;直接溶解法制备HA-Gly-CPT胶束,马尔文激光粒度仪测定胶束粒径、Zeta电位,并考察胶束的稳定性;透射电镜观察胶束的外观;透析法研究其pH响应性体外释放;MTT法检测其抗肿瘤活性.结果 红外光谱、核磁共振氢谱结果确定两亲性聚合物成功合成;HA-Gly-CPT胶束呈球形,平均粒径为(279.86±4.15)nm,Zeta 电位为(-20.17±0.52)mV,在酸性介质中(pH 5.0),HA-Gly-CPT在48 h喜树碱释放度达到50％.MTT实验结果表明HA-Gly-CPT胶束对正常细胞L929生长无影响,而50μg·mL-1 HA-Gly-CPT胶束对肿瘤细胞MCF-7生长抑制率高于80％.结论 成功合成了两亲性聚合物,并制备质量良好且具有pH响应的HA-Gly-CPT胶束.体外实验证明HA-Gly-CPT胶束具有明显的抗肿瘤活性.
Abstract
Objective To synthesize hyaluronic acid-glycine-camptothecin polymer micelles(HA-Gly-CPT micelles),evaluate the quality,and to determine its anti-tumor activity in vitro.Methods Glycine was used to connect hyaluronic acid with camptothecin to form an amphiphilic polymer,whose structure was characterized by IR and 1H-NMR.After preparing the micelles by direct dissolution method,the size,Zeta potential,and stability of the micelles were measured by Malvin laser particle size analyzer.The morphology of nano-micelles was observed by transmission electron microscopy.Dialysis was used to determine its pH responsive drug release in vitro.The anti-tumor activity was determined by MTT assay.Results The structure of HA-Gly-CPT was confirmed by IR and 1H-NMR.The HA-Gly-CPT micelles were spherical with an average particle size of(279.86±4.15)nm and a Zeta potential of(～20.17±0.52)mV.The release rate of camptothecin reached 50％in an acidic medium(pH 5.0)after 48 hours.MTT experiment showed that HA-Gly-CPT micelles had no significant cytotoxicity on the normal L929 cells,while the micelles inhibited the growth of MCF-7 by more than 80％at a concentration of 50 μg·mL-1.Conclusion Amphiphilic polymers and pH responsive HA-Gly-CPT micelles are successfully synthesized,confirming the obvious anti-tumor activity in vitro of HA-Gly-CPT micelles.
关键词
透明质酸/pH响应/喜树碱Key words
hyaluronic acid/pH response/camptothecin引用本文复制引用
出版年
2024
NETL
NSTL
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