ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous P...ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX 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.ResultsThe 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.ConclusionsThis 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.展开更多
基金supported by Capital’s Funds for Health Improvement and Research(CFH:2022-2-5072)the Tianjin Natural Science Foundation for Jingjinji Collaboration(23JCZXJC00240)+1 种基金Beijing Natural Science Foundation(J230006)the CAMS Innovation Fund for Medical Science(2021-I2M-1-052).
文摘ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX 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.ResultsThe 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.ConclusionsThis 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.
