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

作　　者：宋帅恒 杜昊洋 磨莲清 陈续含 包乌日罕 林锋 SONG Shuai-heng;DU Hao-yang;MO Lian-qing;CHEN Xu-han;Bao-wu-ri-han;LIN Feng(Department of Organic Chemistry,College of Pharmacy,Harbin Medical University,Harbin 150081)

机构地区：[1]哈尔滨医科大学药学院有机化学教研室,哈尔滨150081

出　　处：《中南药学》2024年第9期2332-2336,共5页Central South Pharmacy

基　　金：黑龙江省自然科学基金项目(No.LH2020H026);2023年黑龙江省大学生创新创业训练计划项目(No.S202310226007);2023年哈尔滨医科大学大学生创新创业训练计划项目(No.202310226048)。

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50 μg·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。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 50μg·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 

分 类 号：R283[医药卫生—中药学] R285[医药卫生—中医学]