TY - JOUR

T1 - Dexamethasone for Inner Ear Therapy

T2 - Biocompatibility and Bio-Efficacy of Different Dexamethasone Formulations In Vitro

AU - Gao, Ziwen

AU - Schwieger, Jana

AU - Matin-Mann, Farnaz

AU - Behrens, Peter

AU - Lenarz, Thomas

AU - Scheper, Verena

N1 - Funding Information: This study was funded by the BMBF project RESPONSE, Project ID 03ZZ0928L. We acknowledge support by the German Research Foundation (DFG) and the Open Access Publication Fund of Hannover Medical School (MHH) for paying the APC fee.

PY - 2021/12

Y1 - 2021/12

N2 - 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, C22 H29 FO5) and dexamethasone dihydrogen phosphate-disodium (DPS, C22 H28 FNa2 O8 P) 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.

AB - 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, C22 H29 FO5) and dexamethasone dihydrogen phosphate-disodium (DPS, C22 H28 FNa2 O8 P) 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.

KW - Anti-inflammatory

KW - Biocompatibility

KW - Cochlear implant

KW - Dexamethasone

KW - Drug delivery

KW - Fibrosis

KW - LPS

KW - MTT test

KW - TNF-α

UR - http://www.scopus.com/inward/record.url?scp=85121287853&partnerID=8YFLogxK

U2 - 10.3390/biom11121896

DO - 10.3390/biom11121896

M3 - Article

C2 - 34944539

AN - SCOPUS:85121287853

VL - 11

JO - Biomolecules

JF - Biomolecules

IS - 12

M1 - 1896

ER -