Local Application of Drugs to the Inner Ear

Diseases of the inner ear, such as an acute hearing loss with or without tinnitus, belong to the most frequently occurring chronic diseases in Germany. Currently applied therapies include, among others, intravenous infusions; opinions about the effects of these are, however, controversial. Studies have shown that only very high doses of pharmaceuticals yield a measurable level of active agents in the inner ear, which may, however, cause undesirable systemic side effects.

Therefore, medical research has focused for a considerable time now on local therapy methods by which the pharmaceuticals can be taken to the round window membrane in an adequate way, from where they can directly diffuse into the inner ear. At the moment, lacking knowledge about the kinetics of pharmaceuticals in the inner ear is one of the main reasons of uncertainty with respect to the application of this method; therefore, extensive animal testing becomes necessary. However, the morphologic properties of the inner ear of different species also differ, so that the results of animal testing cannot be transferred directly to human beings.

© Fraunhofer ITWM
Simplified three-dimensional geometrical model of the cochlea

A cooperation project between the Department of Otolaryngology, Head and Neck Surgery/Hearing Research Center of the University Hospital Tübingen and the ITWM has now resulted in the development of a mathematical model for the computer simulation of agent distribution in the liquids of the inner ear in the case of a local application of pharmaceuticals. A simplified three-dimensional geometric model of the cochlea has been developed with the software package ANSYS© and used for the simulation of drug application (diffusion process). The necessary physical parameters - permeabilities, diffusion and transition coefficients - were taken from the respective literature as far as they were available.


Inverse Problem connected with Computer Simulations

However, the transition coefficients are generally not very well known; they must therefore be determined by in vivo measurements and the subsequent solution of an inverse problem, in combination with computer simulation. The necessary direct measurement results from animal testing are available in the literature. However, the complete three-dimensional model is not appropriate for real parameter identification due to the required computing time.

Hence, an additional asymptotic one-dimensional model has been developed and implemented which allows for efficient parameter identification. During the evaluation, the ITWM was especially able to prove a considerable scaling error of the measurement results taken from literature. If the respective financial support will be found, the research cooperation can be continued with the development of a realistic model based on CT data.

Type of Project: Industry Project
Project Partner: Klinik für Hals-Nasen-Ohrenheilkunde/ Hörforschungszentrum am Universitätsklinikum Tübingen