Details
| Original language | English |
|---|---|
| Article number | 1896 |
| Number of pages | 14 |
| Journal | Biomolecules |
| Volume | 11 |
| Issue number | 12 |
| Early online date | 17 Dec 2021 |
| Publication status | Published - Dec 2021 |
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, 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.
Keywords
- Anti-inflammatory, Biocompatibility, Cochlear implant, Dexamethasone, Drug delivery, Fibrosis, LPS, MTT test, TNF-α
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
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In: Biomolecules, Vol. 11, No. 12, 1896, 12.2021.
Research output: Contribution to journal › Article › Research › peer review
}
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 -