Examination of Synergistic Effects of Anti-Inflammatory Glucocorticoids and Antifibrotic Antimalarials in an Inner Ear Cell Culture Model

Project Investigators:
Prof. Dr. Stefan Plontke
MLU, Ear, Nose, and Throat Medicine
Prof. Dr. Karsten Mäder
MLU, Pharmaceutical Technology
Prof. Dr. Christian Schmelzer
IMWS, Biological and macromolecular materials
Project summary:
The background of this study is to explore the possibility of a combined administration of anti-inflammatory and antifibrotic drugs to suppress insertion trauma after cochlear implant surgery. We aim to develop biodegradable intracochlear inner ear drug delivery systems IEDDS loaded with antimalarials and glucocorticoids to reduce fibrotic tissue growth in a cell culture model. (1) We will identify therapeutic and tolerated drug concentrations. Various biodegradable IEDDS with drug combinations in selected ratios will be produced using PLGA, PEG-PLGA, or phospholipids as implant matrix. In addition to biodegradable IEDDS, the drugs will also be incorporated into self-made electrode-free cochlear implant arrays made of silicone through mold injection. (2) Physico-chemical characterization of the IEDDS will be performed using microscopic images, X-ray powder diffraction (XRPD), texture analysis, and differential scanning calorimetry (DSC). The surface of the IEDDS will be observed through electron microscopy images after incubation in artificial perilymph buffer. (3) The most promising formulations will be evaluated regarding cytotoxicity and antifibrotic effects during drug release of the IEDDS in cell culture using real-time cell analysis.
