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Nanotechnology and nanomedicine are innovative and rapidly developing areas, aimed to develop nanoscale structures and devices whose physico-chemical properties may be useful for pathological diagnosis and treatment. To date, almost no effective remedies are available for inner ear diseases, i.e. sensorineural hearing loss and vertigo, that are common and disabling conditions caused by the degeneration of sensory-neural transducer epithelial cells and nerve cells. In this scenario, nanotechnology attracted increasing scientific interests for its potential to improve existing treatments, but also raised concerns on possible, still not-fully explored, adverse effects exerted by nanomaterials on the auditory system. Therefore, aim of this work is to provide a comprehensive overview of existing evidence concerning biological interactions between nano-based applications and ear structures.A systematic search and revision of experimental in vitro and in vivo studies addressing possible effects exerted by nano-enhanced remedies on auditory system was performed in the Pubmed, Scopus, and ISI Web of Science databases.Nanoparticle-based systems proved a high potential for inner ear delivery of various therapeutic agents in animal models and were reported to exert a significant protection against drugs- (i.e. cisplatin) as well as noise-induced hearing loss. However, nanomaterials were also able to induce ototoxic effects on cultured cochlear epithelium, as well as middle and inner ear mucosa permeability changes, associated with hearing loss in animals trans-tympanically treated with nanoparticles.Conflicting results emerged concerning nanotechnology applications in otology. Nano-enhanced systems may provide benefits to ear disease treatments, overcoming inner ear anatomic inaccessibility, minimising systemic treatment side effects, allowing a specific and sustained drug release in inner ear fluids. However, other investigations are necessary to deeply assess nano-ototoxicity risks particularly in relation to nanomaterial physico-chemical characterisation, and verify issues of biocompatibility, drug release profile, and biosafety before achieving a successful clinical application.