PLGA nanoparticles in otoprotection and inner ear regeneration: a new frontier in nanomedicine for hearing disorders.

Sensorineural hearing loss (SNHL) remains a significant global health burden due to its irreversible nature and limited treatment options. Recent advances in nanotechnology have introduced new possibilities for targeted drug delivery to the inner ear, with poly(lactic-co-glycolic acid) (PLGA) nanoparticles emerging as a promising platform. Biodegradable and biocompatible, PLGA nanoparticles can encapsulate diverse therapeutic agents and enable sustained, site-specific delivery to cochlear and vestibular structures. This review highlights key physicochemical properties of PLGA nanoparticles relevant to inner ear therapy, including controlled release, tunable surface modifications, and ideal particle size. It explores advanced cochlear targeting techniques-such as round window membrane penetration, magnetic navigation, and ultrasound-assisted delivery-and their applications in otoprotection against ototoxic drugs and noise-induced hearing loss. Additionally, the potential of PLGA nanoparticles in inner ear regeneration, particularly through hair cell restoration and stem cell-based repair, is examined. Preclinical evidence, comparative advantages over other nanocarriers, and challenges in clinical translation are critically reviewed. Finally, emerging trends are discussed, including integration with gene editing, combination therapies, and personalized medicine. This review underscores the transformative potential of PLGA-based nanomedicine in protecting and restoring hearing function, paving the way for future clinical breakthroughs.