Betamethasone phototoxicity: in vitro, in vivo and ex vivo studies

Betamethasone is a synthetic glucocorticosteroid present in numerous systemic and topical commercial formulations for the treatment of rheumatic diseases and skin disorders. The drug is highly unstable under UV light (UVB > UVA) and it has demonstrated moderate photosensitizing activity in patients exposed to solar radiation. Since this drug is taken to treat cutaneous diseases, it’s likely that its induced photosensitization reactions are not always recognized as they are taken for mild sunburn or solar eczemas as well. Three methods (in vitro, in vivo and ex vivo) were used to test drug phototoxicity. The in vitro phototoxicity was determined by exposing Balb/c 3T3 fibroblasts to UVB radiation in the presence of 100 µM drug. The results showed that dark incubation and low UVB dose (0.4 J/cm2) did not affect cell viability. On the contrary, upon exposure to this low UVB dose, Betamethasone was able to induce a decrease of cell viability (30%). In vivo phototoxicity was assayed by means of skin erythema induction in albino guinea pig skin. The drug (200 g) induced skin erythema both when applied as a methanol solution (+/--) and as a commercial formulation (cream containing 0.1% Betamethasone) (++/-). An ex vivo model, epidermis and dermis from isolated pig skin, was also employed. By working both with intact skin and with isolated epidermal cells, it has been possible to determine the extent of intact drug recovery and the cell viability after drug phototreatment. The three methods used gave comparable results and therefore in vitro and ex vivo tests may be an alternative to in vivo phototoxicity studies. From our results, Betamethasone can be considered a photosensitizing drug.