Intratympanic dexamethasone microcrystal-loaded porous PLGA microspheres con-taining lipoic acid for combined delivery to the inner ear
Peili Zhang1
Dongcheng Wang2
Xin Zhang2
Zongyi Wu1
Zhimin Zhou2
Jingjie Wang3
Jianjun Sun4
Mingfang Diao5
1.Department of Otolaryngology,School of Medicine,South China University of Technology,Guangzhou 510006,China;Department of Endoscopic Ear Surgery,Senior Department of Otorhinolaryngology Head and Neck Surgery,The Sixth Medical Center of PLA General Hos-pital,Beijing 100048,China2.Biomedical Barriers Research Center,Institute of Biomedical Engineering,Chinese Academy of Medical Sciences & Peking Union Medical College,Tianjin 300192,China3.State Key Laboratory of Eye Health,Eye Hospital,Wenzhou Medical University,Wenzhou 325027,China4.Department of Otorhinolaryngology Head and Neck Surgery,Peking University International Hospital,Beijing 102206,China5.Department of Otolaryngology,School of Medicine,South China University of Technology,Guangzhou 510006,China;Department of Endoscopic Ear Surgery,Senior Department of Otorhinolaryngology Head and Neck Surgery,The Sixth Medical Center of PLA General Hos-pital,Beijing 100048,China;National Clinical Medical Research Center for Otolaryngology Diseases,Beijing 100048,China
摘要：Objective:To develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).Methods:DEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous PLGA microspheres(LPMPs)were fabricated using a double emulsion-solvent evaporation method.DEX MCs were physically perfused into LPMPs via negative pressure to form a combined system(DEX MCs+LPMPs).Physicochemical properties,in vitro drug release,pharmacokinetics,and biocompatibility were evaluated.Guinea pigs were used for intratympanic injections of DEX MCs,LPMPs,or DEX MCs+LPMPs.Results:The DEX MCs+LPMPs system enabled simultaneous release of both drugs,with DEX exhibiting superior pharmacokinetics(sustained perilymph concentrations up to 7 days)compared to DEX MCs alone.LA release from LPMPs demonstrated prolonged kinetics without burst release.SEM confirmed DEX MCs were localized within/on LPMPs and adhered to the round window membrane(RWM).Histological analysis revealed normal cochlear morphology and no inflammatory response,confirming biocom-patibility.Conclusions:This novel codelivery system combining microcrystals and porous microspheres achieves sustained dual-drug release,enhances therapeutic efficacy,and offers a promising strategy for managing hearing loss via intratympanic administration.
机标关键词：microspheresplgaacidcombinedcon-tainingdeliverydexamethasoneinner
论文发表日期：2025-07-30
在线出版日期：2025-11-07（本平台首次上网日期，不代表文献的发表时间）
页数：8( 190-197 )
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