Intracochlear Delivery of Therapeutics Across RWM via Microneedle Array

Columbia University Health Sciences, New York NY

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): The cochlea is a common site for clinical pathology in our modern society. Tens of thousands of Americans are affected every year by inner ear diseases such as Ménière's, sudden sensorineural hearing loss (SSNHL), and tinnitus. If not treated properly and in a timely manner, these illnesses can have a debilitating, chronic effect on one's hearing or balance, and significantly decrease their quality of life. Unfortunately the cochlea is surrounded by one of the hardest bones in the body, and is quite difficult to reach anatomically. Some currently available treatments for these diseases are limited by their reliance on the medications to reach the inner ear via the bloodstream or through simple diffusion from the middle ear, while others necessitate making destructive holes in the cochlear bone and breaching the scala tympani. Thus, to date no method exists to provide effective, precisely dosed delivery of inner ear therapeutics without risking permanent damage to one's hearing. To circumvent this barrier, the researchers aim to create micro- perforations through the ear's natural round window membrane (RWM) to access the inner ear fluid for drug delivery. The mechanical properties of this border between the middle and inner ears will first be explored to deepen the scientific understanding of the RWM. Techniques such as nanoindentation, laser interferometry, digital microscopy, micro CT (µCT), and high fidelity finit element modeling will be utilized for a complete picture of the RWM properties under both local and global pressures throughout the process of perforation. Based on the results of these studies, various arrays of both solid and hollow silicon microneedles will be designed using isotropic etching and cryogenic processes. These needles will first be tested for their propensity to buckle or bend, and needle design will be optimized for safety during RWM perforation. A series of in vitro then in vivo studies will follow, using guinea pigs as an appropriate animal model. These studies will assess the ability of temporary solid microperforations or microinjection systems through implanted hollow needles to reliably increase the permeability of the RWM. The effect of these needles on RWM histology, the ability of the RWM to heal post-perforation, and the impact of the needles on guinea pig hearing will also be assessed. Finally, the perforations will be analyzed for their ability to consistently provide precise intracochlear drug concentrations. Our animal studies will be followed by the same studies in in vitro, fresh human temporal bone samples, with the ultimate goal of creating a manual mechanical device to deliver microperforations in clinical trials. Once optimized for the specific properties of the human RWM, such a device could allow for safe, quick, effective perforations into the inner ear in the clinic. With the use of hollow needles, this device could both sample inner ear perilymph and inject mediations when necessary, opening up a new realm of inner-ear diagnostics while then providing a means of precise, personalized treatment of often previously idiopathic inner ear pathologies.