Advances and challenges in inner ear drug delivery: limitations and therapeutic perspectives

Hearing loss is a major global health burden, with age-related hearing loss affecting hundreds of millions of people worldwide. Despite significant therapeutic advances, effective treatment remains hampered by the challenge of delivering drugs to the inner ear, an anatomically inaccessible and tightly protected organ.

This narrative review was based on an extensive search of major biomedical databases and focuses on the anatomical and physiological barriers that limit inner ear drug delivery, current and emerging administration routes, and advanced delivery systems, including hydrogels, nanoparticles, microdevices and implantable platforms. Particular attention is given to the factors governing nanocarrier performance and to the key challenges for clinical translation, such as species-dependent pharmacokinetics, manufacturing reproducibility, GMP-compatible scale-up and regulatory requirements. Studies published between 2001 and 2026 were identified through PubMed, Embase, Web of Science and ClinicalTrials.gov.

Despite rapid preclinical innovation, clinical translation remains uneven. Systemic sodium thiosulfate provides the strongest regulatory proof of clinically meaningful otoprotection, whereas recent intracochlear gene therapy establishes an important benchmark for localized treatment. For nanomedicine, progress will depend less on platform novelty than on rational structure-property design, reproducible cochlear exposure, cell-resolved biodistribution, large-animal validation, GMP-compatible manufacturing, patient stratification and clinical trial design.