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

Abstract

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.

Individualized, Additively Manufactured Drug-Releasing External Ear Canal Implant for Prevention of Postoperative Restenosis: Development, In Vitro Testing, and Proof of Concept in an Individual Curative Trial

“…However, although many studies highlight the therapeutic effect of DEX, factors such as the polarity of pro-drugs, the concentration to be applied or the delivery route affect its biological effects. In in vitro studies, the same DEX used as in this study was shown to be biocompatible up to 2000 µM (0.0784 mg/mL) [23]. In addition, this DEX was used for delivery through hydrophobic materials such as silicone in previous studies [24,25].…”

Liquid Crystalline Nanoparticles Conjugated with Dexamethasone Prevent Cisplatin Ototoxicity In Vitro

“…Dexamethasone is a glucocorticoid with anti-inflammatory and antioxidant properties widely used in hearing loss treatment but also in basic research [ 53 , 54 ]. However, it is known that systemic administration can cause numerous side effects due to steroids accumulation.…”

“…However, it is known that systemic administration can cause numerous side effects due to steroids accumulation. For this reason, local administration, for example, through the tympanic membrane, is preferred for the inner ear [ 54 , 55 ]. In the recent literature, there is an increasing number of studies in which dexamethasone is spread through the electrode of cochlear implants [ 56 , 57 , 58 ].…”

Long term behavior of dexamethasone-loaded cochlear implants: In vitro & in vivo

“…To overcome these drawbacks, the local release of low amounts of dexamethasone over prolonged periods of time has been proposed ( Astolfi et al, 2016 ; Bas et al, 2016 ; Douchement et al, 2015 ; Qnouch et al, 2021 ). Several beneficial effects of such a glucocorticoid treatment can be expected: (i) The importance of inflammation caused by implant placement can be reduced, (ii) fibrosis be limited, and (iii) the life-time expectancy of remaining hair cells be increased ( Jia et al, 2016 ; Liu et al, 2015 ; Gao et al, 2021 ; Toulemonde et al, 2021 ). One possible strategy is to incorporate dexamethasone into the silicone matrices separating the metal electrodes in the cochlear implants ( Farahmand Ghavi et al, 2010 ; Krenzlin et al, 2012 ; Farhadi et al, 2013 ; Liu et al, 2016 ).…”