Dexamethasone-loaded lipid-polymeric nanoparticles to improve therapy for cisplatin-induced sensorineural hearing loss

Abstract

Sensorineural hearing loss (SNHL), caused by ototoxic drugs like cisplatin, poses significant challenges due to its irreversible nature. Dexamethasone, a potent corticosteroid, is commonly used to mitigate SNHL but suffers from systemic side effects and poor inner ear bioavailability when administered conventionally. This study explores the potential of dexamethasone-loaded lipid-polymeric nanoparticles (LPNs) to enhance drug delivery efficiency and therapeutic outcomes. The LPNs were fabricated using stearic acid and poly (lactic-co-glycolic acid) (PLGA) via a double emulsion solvent evaporation method, combining the biocompatibility of lipid nanoparticles with the sustained-release properties of polymeric nanoparticles. Characterization revealed optimal particle size (∼150 nm by SEM and ∼380 nm by LDE), polydispersity index (PDI 0.233), and ζ-potential (−21.9 mV), ensuring colloidal stability and cellular uptake. In vitro studies demonstrated sustained dexamethasone release over 72 hours, with 55.56% released within 4 hours. HEI-OC1 cell viability assays confirmed the LPNs' cytocompatibility and superior protection against cisplatin-induced cytotoxicity compared to raw dexamethasone. In vivo experiments in a cisplatin-induced ototoxicity mouse model showed enhanced cochlear drug distribution, peaking at 24 hours, and significantly reduced auditory brainstem response (ABR) thresholds at 16 kHz and 32 kHz post-intratympanic injection. These findings highlight the LPNs' potential as a targeted, sustained-release delivery system for treating SNHL, offering improved efficacy and reduced systemic exposure. This study provides a foundation for clinical translation of LPN-based therapies in otoprotection.