Photoactivation of corticosteroids in UVB-exposed skin

The photodegradation of flumethasone (FM) and fluocinolone acetonide (FC) was studied in solution and
in the pig skin. Both glucocorticosteroids applied to the pig skin were unstable under UVB light. The
photoproducts formed in the skin were the lumi-, photolumi- and andro-derivatives for FM, the same
found in vitro. Instead, FC hydroperoxide formed in solution was not found in the skin: the reactivity
and oxidative ability of this photoproduct towards biological substrates (lipids, proteins) seems the reason
of the lack of its detection in the ex vivo model. In fact, it demonstrated to quickly oxidize amino acids
and peptides, and to react with BSA both in the dark and under irradiation. Moreover, the presence in the
irradiated pig skin of the FC andro-derivative, which usually forms in H-donating environment, seems
consistent with the mechanism of Norrish I fragmentation followed by H-abstraction, likely from the surrounding
biological substrates. These findings indicate that photoreactivity of these compounds may take
place in the skin of patients exposing themselves to sunlight and is a warning about possible skin damage
as a result of that. Furthermore, photolability of these drugs in the skin might cause loss of their therapeutic
activity.