Intratympanic dexamethasone microcrystal-loaded porous PLGA microspheres con-taining lipoic acid for combined delivery to the inner ear
Peili Zhang
Dongcheng Wang
Xin Zhang
Zongyi Wu
Zhimin Zhou
Jingjie Wang
Jianjun Sun
Mingfang Diao
Abstract：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 biocompatibility. 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.
Keywords：PLGA porous microspheresdexamethasone microcrystalslipoic acidinner ear delivery
Publication Date：2025-07-30
Online Publishing Date：2025-11-07(First online date of this platform, not the publication date of the document)
Pages：8( 190-197 )