聚氨基酸纳米水凝胶负载地塞米松的内耳递送研究  

Inner Ear Delivery of Polyamino Acid Nanohydrogels Loaded with Dexamethasone

作　　者：艾苹苹 赵立东 汤朝晖[8] 贺超良[8] 陈学思[8] 杨仕明[2,3,4,5,6,7] 吴南 AI Pingping;ZHAO Lidong;TANG Zhaohui;HE Chaoliang;CHEN Xuesi;YANG Shiming;WU Nan(Zhejiang Chinese Medical University,Hangzhou 310053,China;Senior Department of Otolaryngology Head and Neck Surgery,the 1st Medical Center of Chinese PLA General Hospital,Beijing 100853,China;State Key Laboratory of Hearing and Balance Science,Beijing 100853,China;National Clinical Research Center for Otolaryngologic Diseases,Beijing 100853,China;Senior Department of Otolaryngology Head and Neck Surgery,the 6th Medical Center of Chinese PLA General Hospital,Beijing 100853,China;Key Laboratory of Hearing Science,Ministry of Education,Beijing 100853,China;Beijing Key Laboratory of Hearing Impairment Prevention and Treatment,Beijing 100853,China;Changchun Institute of Applied Chemistry Chinese Academy of Sciences,Changchun 130022,China)

机构地区：[1]浙江中医药大学,杭州310053 [2]中国人民解放军总医院第一医学中心耳鼻咽喉头颈外科,北京100853 [3]听觉与平衡觉全国重点实验室,北京100853 [4]国家耳鼻咽喉疾病临床医学研究中心,北京100853 [5]中国人民解放军总医院第六医学中心耳鼻咽喉头颈外科医学部,北京100853 [6]聋病教育部重点实验室,北京100853 [7]聋病防治北京市重点实验室,北京100853 [8]中国科学院长春应用化学研究所,长春130022

出　　处：《协和医学杂志》2025年第2期370-378,共9页Medical Journal of Peking Union Medical College Hospital

基　　金：国家重点研发计划(2022YFC2402701)。

摘　　要：目的 构建一种用于地塞米松内耳递送的新型聚氨基酸纳米水凝胶给药系统,以提高地塞米松给药效率。方法 合成经荧光标记的基于聚谷氨酸的聚氨基酸地塞米松纳米药物水凝胶,并测试其凝胶化时间。在此基础上,通过手术将水凝胶注射于豚鼠的圆窗龛,测定其在活体豚鼠中耳腔内的降解时间,并评价该给药系统的安全性、药代动力学及地塞米松在内耳中的分布规律。结果 在37℃水浴锅中,该水凝胶的凝胶化时间为80 s;在活体豚鼠中耳腔内,水凝胶7 d内基本可完全降解。中耳腔给药1 d后豚鼠出现一过性听力损失,随着时间延长,听力逐渐恢复正常。未观察到该水凝胶具有明显的细胞毒性,未见豚鼠具有前庭功能刺激体征,病理学检测亦未见螺旋神经节细胞具有异常改变和明显的炎症反应。药代动力学显示,该水凝胶具有药物缓释作用,并可延长地塞米松作用时间。免疫荧光染色显示,地塞米松在耳蜗和前庭器官中均有明显分布。结论 聚氨基酸纳米水凝胶具有良好的可注射性和可降解性,是一种安全、有效的内耳药物递送系统。Objective To develop a novel polyamino acid⁃based nanohydrogel drug delivery system for dexa⁃methasone to enhance its delivery efficiency to the inner ear.Methods A fluorescein⁃labeled polyglutamic acid⁃based polyamino acid dexamethasone nanohydrogel was synthesized,and its gelation time was measured.The hydrogel was surgically injected into the round window niche of guinea pigs to determine its degradation time in the middle ear cavity in vivo.The safety,pharmacokinetics,and distribution patterns of dexamethasone in the inner ear were evaluated.Results The hydrogel exhibited a gelation time of 80 seconds in a 37℃water bath.In vivo,the hydrogel was almost completely degraded within 7 days in the middle ear cavity of guinea pigs.Transient hearing loss was observed one day after administration,but hearing gradually returned to normal over time.No significant cytotoxicity,vestibular stimulation signs,or pathological abnormalities in spiral ganglion cells were observed.Histopathological examination revealed no significant inflammatory reactions.Pharmacoki⁃netic analysis demonstrated sustained drug release and prolonged dexamethasone activity.Immunofluorescence staining confirmed the distribution of dexamethasone in both the cochlea and vestibular organs.Conclusion The polyamino acid nanohydrogel exhibits excellent injectability and biodegradability,representing a safe and effective drug delivery system for the inner ear.

关 键 词：聚氨基酸 纳米水凝胶 地塞米松 耳科学 药代动力学 

分 类 号：R318[医药卫生—生物医学工程] R764[医药卫生—基础医学]