Inner ear drug delivery for auditory applications

Abstract

Many inner ear disorders cannot be adequately treated by systemic drug delivery. A blood-cochlear barrier exists, similar physiologically to the blood-brain barrier, which limits the concentration and size of molecules able to leave the circulation and gain access to the cells of the inner ear. However, research in novel therapeutics and delivery systems has led to significant progress in the development of local methods of drug delivery to the inner ear. Intratympanic approaches, which deliver therapeutics to the middle ear, rely on permeation through tissue for access to the structures of the inner ear, whereas intracochlear methods are able to directly insert drugs into the inner ear. Innovative drug delivery systems to treat various inner ear ailments such as ototoxicity, sudden sensorineural hearing loss, autoimmune inner ear disease, and for preserving neurons and regenerating sensory cells are being explored.

Figure 1

(a) A mid-modiolar section from a human temporal bone indicates the coiled structure of the cochlea as it winds around a central modiolus, which contains the spiral (auditory) ganglion and its associated auditory nerve fibers. (b) Each segment contains 3 fluid filled structures, the scala tympani (s.t.), scala media (s.m.), and scala vestibuli (s.v.). The organ of Corti, which contains the sensory cells of the cochlea (hair cells), separates the scala media and the scala tympani with the apical surface of the epithelium facing the fluid space of the scala media and all other cell surfaces bathed in perilymph of the scala tympani. The scala vestibuli is the fluid space at the upper portion of each turn. The outer edge of each turn is occupied by the spiral ligament, which is in diffusional continuity with perilymph. The outer edge of the scala media is bordered by the stria vascularis. The scala tympani and scala vestibuli are joined at the apical extreme of the cochlea at the helicotrema. The cochlear aqueduct connects the fluid space of the scala tympani with the cerebrospinal fluid space.