摘要
目的制备姜黄素氧化型前药胶束,评估其预防药源性听力损失的活性。方法将难溶性药物姜黄素与亲水性聚乙二醇通过氧化响应的单硫键进行化学偶联,得到具有两亲性的姜黄素氧化型前药,并采用氢谱、紫外、红外及荧光等对前药进行表征;利用前药的两亲性,在水溶液中自组装制备成姜黄素氧化型前药胶束,对其粒径、形貌及电位进行表征和考察,采用细胞模型和动物模型评估胶束预防药源性听力损失的效果。结果氢谱、紫外光谱表征及临界胶束浓度、粒径测定,确证了化合物的成功合成及胶束的成功制备;在小鼠耳蜗毛细胞系(HEI-OC1)细胞模型上,姜黄素氧化型前药胶束能够很好地预防顺铂诱导的毛细胞损伤,与同浓度下的单独姜黄素相比有更好的保护效果;豚鼠模型上,该前药胶束对毛细胞均有良好的保护效果,都能够提高姜黄素的耳保护效果。结论成功制备了姜黄素氧化型前药胶束,该胶束具有较好的耳保护效果。
Objective To synthesize oxidation-responsive curcumin prodrug micelles and evaluate their protective effect in preventing drug-induced hearing loss.Methods An amphiphilic curcumin prodrug was synthesized by conjugating curcumin to polyethylene glycol(PEG)via an oxidation-sensitive mono-sulfide.The prodrug was characterized by 1H NMR,UV-Vis,FT-IR,and fluorescence spectroscopy.Subsequently,the amphiphilic prodrug self-assembled in aqueous solution to form curcumin oxidation-responsive micelles,which were further characterized for particle size,morphology,and Zeta potential.The otoprotective efficacy was evaluated in vitro(HEI-OC1 cells)and in vivo(guinea pigs)models of cisplatin-induced ototoxicity.Results The successful synthesis of the compound and the preparation of the micelles were confirmed by hydrogen spectra,ultraviolet spectra,as well as the determination of critical micelle concentration and particle size.In the mouse cochlear hair cell line(HEI-OC1)cell model,the curcumin oxidation-responsive micelles significantly prevented cisplatin-induced hair cell damage,demonstrating superior protection compared to free curcumin at equivalent concentrations.In guinea pigs,the prodrug micelles also demonstrated significant protective efficacy on hair cells,enhancing the otoprotective efficacy of curcumin.Conclusion Curcumin oxidation-responsive prodrug micelles were successfully developed and demonstrated potent protective effects against drug-induced ototoxicity.
作者
魏美玲
魏楠
冯晓华
李志扬
温露
李华安
陈钢
WEI Meiling;WEI Nan;FENG Xiaohua;LI Zhiyang;WEN Lu;LI Hua′an;CHEN Gang(Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations,School of Pharmacy/New Drug Research and Development Center,Guangdong Pharmaceutical University,Guangzhou 510006,China;Department of Otolaryngology Head and Neck Surgery,General Hospital of Southern Theater Command of PLA,Guangzhou 510010,China)
出处
《广东药科大学学报》
2025年第6期1-10,共10页
Journal of Guangdong Pharmaceutical University
基金
国家自然科学基金项目(82474092)
广州市重点研发计划项目(2023B03J1293)
广东省普通高校创新团队项目(2024KCXTD035)
广东省研究生教育创新计划项目(2022SFKC072)。
关键词
前药
胶束
姜黄素
氧化响应性
药源性听力损失
prodrug
micelles
curcumin
oxidative responsiveness
drug-induced ototoxicity
