How Effective are Exosomes in Overcoming Blood-Labyrinth Barrier in Sensorineural Hearing Loss? A Comprehensive Review of the Literature

Sensorineural hearing loss (SNHL) is a prevalent global health issue, and its pharmacological treatment is severely hindered by the blood-labyrinth barrier (BLB). Exosomes, natural extracellular vesicles (30-150 nm), have emerged as a highly promising nanoplatform to overcome this delivery challenge. Their innate biocompatibility, low immunogenicity, and ability to cross biological barriers make them ideal for targeted drug delivery. This review examines the inner ear barrier systems and elucidates the mechanisms, such as receptor-mediated transcytosis, by which exosomes can traverse the BLB. It further discusses engineering strategies to optimize drug loading, enhance targeting, and improve therapeutic efficacy for SNHL. The application of engineered exosomes in delivering diverse cargoes-including nucleic acids, proteins, and small-molecule drugs-is comprehensively reviewed, highlighting their potential in preclinical models to preserve auditory function. Despite this promise, significant challenges remain in standardization, scalable production, loading efficiency, long-term safety, and clinical translation. Future research should focus on refining engineering techniques, elucidating in vivo pharmacokinetics, and advancing preclinical studies to facilitate the clinical adoption of exosome-based therapies, ultimately offering a novel and precise paradigm for SNHL treatment.