title: Photoactivation of corticosteroids in UVB-exposed skin.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Padova, Italy. giorgia.miolo@unipd.it
authors.forename: G
authors.initials: G
authors.lastname: Miolo
authors.forename: S
authors.initials: S
authors.lastname: Caffieri
authors.forename: D
authors.initials: D
authors.lastname: Dalzoppo
authors.forename: F
authors.initials: F
authors.lastname: Gallocchio
authors.forename: E
authors.initials: E
authors.lastname: Fasani
authors.forename: G M J
authors.initials: GM
authors.lastname: Beyersbergen van Henegouwen
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002417:Cattle; D005443:Flumethasone / Q000737:chemistry* / Q000378:metabolism; D005446:Fluocinolone Acetonide / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D010455:Peptides / Q000378:metabolism; D010782:Photolysis / Q000528:radiation effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D000596:Amino Acids; D010455:Peptides; D017382:Reactive Oxygen Species; D005446:Fluocinolone Acetonide; D012710:Serum Albumin, Bovine; D005443:Flumethasone