Cytotoxicity and antifungal effects of combined dexamethasone and miconazole on human oral keratinocytes, gingival fibroblasts, and Candida albicans

Abstract

Oral lichen planus (OLP), a prevalent immune-mediated inflammatory condition, requires effective therapies. Topical corticosteroids, such as dexamethasone, are widely used for OLP treatment. However, they can predispose patients to secondary candidiasis, necessitating adjunctive therapy with antifungal agents like miconazole. Little is known about the cellular dynamics and toxicity of the combined use of dexamethasone and miconazole. This study examined the effect of dexamethasone on the antifungal activity of miconazole against Candida albicans and the effect of miconazole on the immunosuppressive activity of dexamethasone on human T cells. The cytotoxicity of dexamethasone alone and dexamethasone combined with miconazole on human oral keratinocytes and gingival fibroblasts was also determined using both in vitro monolayer and Transwell co-culture models. A 5-min incubation thrice daily cell treatment protocol was employed for all assays. Dexamethasone did not affect miconazole’s antifungal efficacy, and a single exposure of miconazole inhibited over 99% of C. albicans growth. In monolayer cultures, 0.05% dexamethasone was non-toxic to keratinocytes and fibroblasts, while miconazole exhibited dose-dependent cytotoxicity at high concentrations. Transwell co-culture models confirmed this dose-dependent cytotoxicity, with higher miconazole concentrations causing increased apoptosis. Dexamethasone significantly reduced T cell viability, activation, and proliferation, unaffected by miconazole co-treatment. In conclusion, when used in combination at optimal concentrations, miconazole’s antifungal activity and dexamethasone’s anti-T-cell proliferation activity are retained without cytotoxicity to human oral cells. Further research is needed to validate these findings and develop evidence-based treatments for oral lichen planus.