Intratympanic dexamethasone microcrystals/lidocaine-loaded PLGA non-spherical microparticles for local drug delivery to the inner ear.

BACKGROUND: Sudden sensorineural hearing loss (SSNHL), often associated with tinnitus, significantly impacts individuals' quality of life. Current treatments, such as free drugs via intravenous or intratympanic (IT) administration of dexamethasone (DEX) and lidocaine, face limitations like low bioavailability and rapid drug clearance. To address these challenges, we developed a local co-delivery system combining DEX microcrystals (DEX MCs) and lidocaine-loaded poly(lactic-co-glycolic acid) (PLGA) non-spherical microparticles (LPNMs) for sustained drug release in the inner ear. METHODS: DEX MCs and LPNMs were prepared using the traditional precipitation technique and double emulsion-solvent evaporation, respectively. After characterizing physicochemical properties and drug release kinetics, they were dispersed in sodium hyaluronate solution for IT injection, then in vivo pharmacokinetics and biocompatibility in guinea pigs were studied. RESULTS: DEX MCs exhibited stable dissolution, while LPNMs provided sustained lidocaine release, reducing potential side effects. In vivo studies in guinea pigs demonstrated prolonged drug retention in the perilymph and improved pharmacokinetics. Histological evaluation confirmed the good biocompatibility of this combined delivery system, with no significant inner ear damage observed. CONCLUSION: This co-delivery system can be used as a depot for delivering both DEX and lidocaine to the inner ear and offers a promising approach for the synergistic treatment of SSNHL associated with tinnitus.