Overcoming barriers: a review on innovations in drug delivery to the middle and inner ear

Abstract

Despite significant advances in the development of therapeutics for hearing loss, drug delivery to the middle and inner ear remains a challenge. As conventional oral or intravascular administration are ineffective due to poor bioavailability and impermeability of the blood-labyrinth-barrier, localized delivery is becoming a preferable approach for certain drugs. Even then, localized delivery to the ear precludes continual drug delivery due to the invasive and potentially traumatic procedures required to access the middle and inner ear. To address this, the preclinical development of controlled release therapeutics and drug delivery devices have greatly advanced, with some now showing promise clinically. This review will discuss the existing challenges in drug development for treating the most prevalent and damaging hearing disorders, in particular otitis media, perforation of the tympanic membrane, cholesteatoma and sensorineural hearing loss. We will then address novel developments in drug delivery that address these including novel controlled release therapeutics such as hydrogel and nanotechnology and finally, novel device delivery approaches such as microfluidic systems and cochlear prosthesis-mediated delivery. The aim of this review is to investigate how drugs can reach the middle and inner ear more efficiently and how recent innovations could be applied in aiding drug delivery in certain pathologic contexts.

Cutting‐Edge Achievements of Inner Ear Drug Delivery Systems

“…Reproduced with permission. [8] Copyright 2023, Delaney, Liew, Lye, Atlas and Wong. Frontiers Media S.A. All rights reserved.…”

“…Copyright 2004, Springer Nature b) Illustration of BLB composed of pericytes, endothelial cells, and macrophages, surrounding the capillaries within the intermediate cell layer of the vascular striae. Reproduced with permission [8]. Copyright 2023, Delaney, Liew, Lye, Atlas and Wong.…”

Recent Therapeutic Progress and Future Perspectives for the Treatment of Hearing Loss

“…Gene transfection with nanoparticles tends to be less durable than with AAV, although this may not be a disadvantage where the prolonged expression of an exogenous gene may cause unwanted effects [79]. We and others have recently reviewed how nanoparticles are formulated for various therapeutic applications to the inner ear, which we would recommend to the interested reader as that is beyond the scope of this review [57,80]. Briefly, nanoparticles can largely be categorized as lipidic or inorganic, with the former being the more established for general nanomedicine.…”