Engineered Inner Ear Drug Delivery Systems for Hearing Loss Treatment.

Hearing loss is becoming a common disease worldwide, affecting individuals across all age groups, from infants to older adults. However, the unique anatomical barriers of the inner ear limit the effectiveness of conventional systemic therapies, highlighting the need for advanced drug delivery strategies. Engineered inner ear drug delivery systems have emerged as promising approaches for improving drug targeting, retention, and therapeutic efficacy. In this review, we provide a comprehensive overview of the advances by integrating 3 major aspects: major administration routes, diverse therapeutic agents, and delivery carriers employed in inner ear treatment. We first introduce systemic administration, trans-tympanic drug delivery, intracochlear drug delivery, and cochlear implantation (CI). We then summarize anti-inflammatory drugs and antioxidants for the treatment of inner ear disorders. Subsequently, we discuss multiple nanocarriers, viral vectors, injectable hydrogels, and other innovative carriers used in inner ear drug delivery, highlighting their design principles and therapeutic applications. We also illustrate recent progress in clinical trials and discuss the difficulties associated with translating experimental systems into clinical applications. Finally, we outline current limitations and future opportunities, together with potential strategies to address these challenges.