Aspirin in Audiology: A Dual-Edged Sword in Hearing Loss and Its Nanotechnology-Driven Future.

Globally, more than 1.6 billion individuals are affected by hearing loss. Aspirin (acetylsalicylic acid, ASA), an inexpensive and widely available drug, has demonstrated a complex dual role in hearing loss, with its effects potentially influenced by dosage and individual variability. In this article, we aimed to provide an overview of the pharmacological properties of aspirin, followed by an in-depth discussion of its mechanisms of action and its toxic and protective effects in different types of pathology-induced hearing loss. Finally, the development of novel drug delivery systems that may enhance the use of this drug in preventing hearing loss was also discussed. Aspirin exerts both ototoxic and protective effects via cyclooxygenase (COX)-dependent and COX-independent signaling pathways, including Wingless/Integrated (Wnt) signaling, nuclear factor kappa-B (NF-κB), and Prestin-related mechanisms. Low-dose aspirin appears to reduce hearing damage from noise exposure or ototoxic drugs through anti-inflammatory and antioxidant actions that limit cochlear oxidative stress and inflammation. Conversely, higher doses of aspirin may induce reversible auditory changes, such as temporary hearing threshold shifts, tinnitus, and synaptic damage. These effects are primarily associated with cochlear ischemia, excessive activation of N-methyl-D-aspartate (NMDA) receptors, impaired prostaglandin signaling, and altered outer hair cell function resulting from Prestin modulation. This dose-dependent paradox presents a major challenge for the clinical application of aspirin in hearing protection. Nanotechnology-based delivery systems and personalized dosing strategies are promising, although they remain largely at the preclinical stage. Future work should concentrate on optimizing doses and targeting drug delivery to cochlear blood vessels or outer hair cells. Particular attention should be given to aspirin's role in COX signaling pathways and Prestin structural regulation. Overall, these findings provide a theoretical basis for precision-based ear protection strategies, pending clinical validation.