Dexamethasone for Inner Ear Therapy: Biocompatibility and Bio-Efficacy of Different Dexamethasone Formulations In Vitro

Biomolecules

Peter Behrens¹  Ziwen Gao²  Jana Schwieger²  Farnaz Matin-Mann²  Thomas Lenarz²  Verena Scheper² 

[1] Cluster of Excellence “Hearing4all” EXC 1077/2, 30625 Hannover, Germany;Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Department of Otorhinolaryngology, Head and Neck Surgery, Hanover Medical School, Stadtfelddamm 34, 30625 Hannover, Germany;

关键词: cochlear implant;    dexamethasone;    LPS;    TNF-α;    fibrosis;    anti-inflammatory;   

DOI  :  10.3390/biom11121896

来源: DOAJ

【 摘 要 】

Dexamethasone is widely used in preclinical studies and clinical trials to treat inner ear disorders. The results of those studies vary widely, maybe due to the different dexamethasone formulations used. Laboratory (lab) and medical grade (med) dexamethasone (DEX, C₂₂H₂₉FO₅) and dexamethasone dihydrogen phosphate-disodium (DPS, C₂₂H₂₈FNa₂O₈P) were investigated for biocompatibility and bio-efficacy in vitro. The biocompatibility of each dexamethasone formulation in concentrations from 0.03 to 10,000 µM was evaluated using an MTT assay. The concentrations resulting in the highest cell viability were selected to perform a bio-efficiency test using a TNFα-reduction assay. All dexamethasone formulations up to 900 µM are biocompatible in vitro. DPS-lab becomes toxic at 1000 µM and DPS-med at 2000 µM, while DEX-lab and DEX-med become toxic at 4000 µM. Bio-efficacy was evaluated for DEX-lab and DPS-med at 300 µM, for DEX-med at 60 µM, and DPS-lab at 150 µM, resulting in significantly reduced expression of TNFα, with DPS-lab having the highest effect. Different dexamethasone formulations need to be applied in different concentration ranges to be biocompatible. The concentration to be applied in future studies should carefully be chosen based on the respective dexamethasone form, application route and duration to ensure biocompatibility and bio-efficacy.

【 授权许可】

Unknown