Advancing Otology through Nanoparticle-Based Interventions for Inner Ear Treatment

Globally, more than 430 million individuals are affected by debilitating hearing loss (HL), yet effective inner ear drug delivery remains limited by the blood–labyrinth barrier and the low permeability of the round window membrane (RWM). Nanoparticle (NP)-based platforms offer a transformative approach to overcoming these barriers through targeted, sustained delivery of therapeutic agents directly to inner ear structures. This review provides a comprehensive overview of nanotechnology applications in otology, encompassing otoprotective and regenerative therapeutic paradigms. Key physicochemical design principles are examined, including the relationship between particle size (optimal 100–200 nm), surface charge, and hydrophilicity with RWM penetration and cochlear distribution. Organic, inorganic, and hybrid NP platforms are evaluated for drug delivery, growth factor delivery, and diagnostic imaging. Surface functionalization strategies enabling cell-specific targeting of outer hair cells and spiral ganglion neurons are discussed. The review also addresses nanotechnology-enhanced cochlear implants, nanofiber scaffolds for tissue reconstruction, and nanoparticle-mediated gene therapy, contextualized alongside recent landmark clinical trials of adeno-associated virus (AAV)-mediated gene therapy for hereditary HL. Despite encouraging preclinical outcomes, no NP-based therapeutic strategy for inner ear disorders has progressed to human clinical trials, underscoring persistent challenges related to long-term biocompatibility and safety, interspecies translational variability, and large-scale manufacturing reproducibility. Potential strategies to overcome these translational barriers and facilitate clinical implementation are further discussed.