Local Delivery of Therapeutics to the Cochlea Using Nanoparticles and Other Biomaterials

Hearing loss negatively impacts the well-being of millions of people worldwide. Systemic delivery of ototherapeutics has limited efficacy due to severe systemic side effects and the presence of the blood-labyrinth barrier that selectively limits or enables transfer of molecules between plasma and inner ear tissues and fluids. Local drug delivery into the middle and inner ear would be preferable for many newly emerging classes of drugs. Although the cochlea is a challenging target for drug delivery, recent technologies could provide a safe and efficacious delivery of ototherapeutics. Local drug delivery routes include topical delivery via the external auditory meatus, retroauricular, transtympanic, and intracochlear delivery. Many new drug delivery systems specifically for the inner ear are under development or undergoing clinical studies. Future studies into these systems may provide a means for extended delivery of drugs to preserve or restore hearing in patients with hearing disorders. This review outlines the anatomy of the (inner) ear, describes the various local delivery systems and routes, and various quantification methodologies to determine the pharmacokinetics of the drugs in the inner ear.