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.

Ear as an alternative way for brain drug targeting: An Overview

“…Movement of the the basilar membrane by pressure changes induced by stapes footplate motion at the oval window is a critical step in the transduction process. If you cut the cochlear tube cross sectionally, you'd see something like this Scala vestibuli on top, scala tympani on the bottom [16]. Scala media is a triangular duct in the middle.…”

“…Most of the structures of the cochlea are in diffusional continuity with the perilymph [16]. Thus, a drug placed into the perilymph can diffuse into the organ of Corti, which contains hair cells, neuronal terminals, and other specialized cells.…”

“…Animal studies have shown that the perilymphatic fluid physiologically flows from the inner ear to the CSF in the subarachnoid compartment of the brain. An animal study that investigated the feasibly of using the inner ear as a delivery route to the CSF has shown that dexamethason acetate loaded to solid-lipid nanoparticles (SLN) effectively transports to the CSF following trans-tympanic injection [16]. Shulman A et.…”

Intratympanic Corticosteroid for Neurosensorial Hearing Loss Treatment

“…There is exchange between the different compartments of the inner ear: between tympanic perilymph and vestibular perilymph and between endolymph and perilymph. But also between the inner ear fluids and cerebrospinal fluid and between the inner ear fluid and plasma (12) (13). Exchanges between endolymph and plasma are through the stria vascularis and between perilymph and plasma through the capillaries perilymphatic.…”

Two-photon microscopy of the mouse cochleain situfor cellular diagnosis

“…Most hearing loss, including noise-induced and age-related hearing loss, starts and is most prominent in the cochlear region close to the round window. Accessing the round window has been of intense interest for vibratory transducer implants, 2 intra-tympanic drug delivery, 3,4 and cochlear implants. 5 Optical techniques are particularly well-suited for imaging of the delicate intracochlear structures because they offer a significantly higher spatial resolution and lower cost compared with CT 6 and MRI 7 scans.…”