CUR-SS-PEG-HA前药胶束制备及其还原敏感控释性能评价  

Fabrication of nanoscale CUR-SS-PEG-HA prodrug micelles and characterization of their redox trigged controlled release behavior

作　　者：彭佳佳 黄赛朋[1] 闫宇斌 蒋萌 高婷[1] 薛伟明[1] 温惠云[1] PENG Jiajia;HUANG Saipeng;YAN Yubin;JIANG Meng;GAO Ting;XUE Weiming;WEN Huiyun(School of Chemical Engineering,Northwest University,Xi′an 710069,China)

机构地区：[1]西北大学化工学院,陕西西安710069

出　　处：《西北大学学报（自然科学版）》2021年第2期296-302,共7页Journal of Northwest University（Natural Science Edition）

基　　金：陕西省自然科学基础研究计划基金资助项目(2018JM2037);教育部重点实验室开放基金资助项目(ZSK2018008)。

摘　　要：利用肿瘤细胞内的高水平还原型谷胱甘肽(GSH)环境特征,该文将抗肿瘤药物姜黄素(CUR)通过二硫键连接到亲水性透明质酸(HA)和聚乙二醇(PEG)分子上,构建了对GSH具有还原敏感刺激响应的CUR-SS-PEG-HA前药纳米胶束。FT-IR和1H-NMR分析结果证明疏水性CUR分子被成功键合在亲水聚合物骨架上。CUR-SS-PEG-HA前药胶束的临界胶束浓度(CMC)为0.098 mg/mL,载药量达到19.74%(w/w);动态光散射法测得胶束平均水合粒径为438 nm,Zeta电位为-23.5 mV;透射电镜观测到尺寸均一且单分散性良好的球形纳米胶束。模拟肿瘤细胞内高浓度GSH环境,在10 mmol/L GSH溶液中观测到前药胶束尺寸显著增大和溶液荧光强度显著增强,CUR从胶束中释放的速率比不含GSH的对照样品快7倍左右。因此,还原敏感聚合物前药胶束可以为设计肿瘤治疗新方案提供有益借鉴。In this study,a redox-sensitive prodrug micelle(CUR-SS-PEG-HA)was designed for drug delivery due to high glutathione(GSH)level in tumor cells.Specifically,anticancer drug curcumin(CUR)was connected on hydrophilic hyaluronic acid(HA)and polyethylene glycol(PEG)blocks via disulfide linkage.FT-IR and 1H-NMR showed successful conjugation of CUR on hydrophilic blocks via disulfide linkage.The CMC value of prepared CUR-SS-PEG-HA prodrug micelles was 0.098 mg/mL.The loading efficiency was 19.74%(w/w).DLS measurements showed the prodrug micelles had an average size of 438 nm in diameter.The zeta potential was-23.5 mV.Furthermore,TEM confirmed the prodrug micelles with uniform size and good monodispersity.The prodrug micelles size and fluorescence intensity both significantly increased in the presence of tumor relevant GSH(10 mmol/L).Moreover,the prodrug micelles showed high GSH sensitivity which accelerate in vitro release of CUR from micelles 7 times faster than in absence of GSH.Thus,these redox-sensitive prodrug micelles may provide a useful reference for the design of new tumor treatment programs.

关 键 词：姜黄素 前药胶束 还原敏感响应 药物释放 

分 类 号：O631[理学—高分子化学]