RESUMO
This study aimed to assess the phototoxic potential of combined UV-filters and retinyl palmitate (RP) in the presence or not of bemotrizinol (BMTZ), employing photostability and in vitro and in vivo phototoxicity assays. The formulations tested contained octocrylene (OCT), octyl methoxycinnamate (OMC), benzophenone-3 (BZP-3) and RP (photostable) or octocrylene (OCT), octyl methoxycinnamate (OMC), avobenzone (AVO) and RP (less photostable). Both formulations were supplemented with bemotrizinol. Photostability was evaluated by exposing, or not, formulations spread on a glass plate to UVA/UVB irradiation. The resulting products were quantified by HPLC analysis. In vitro phototoxicity of UV-filters and combinations were evaluated using 3T3 viable monolayer fibroblast cultures submitted, or not, to irradiation according to OECD TG 432. In vivo photoallergy and photoxicity were assessed by clinical studies (photopatch test). Photostability assays showed that UV-filter bemotrizinol was a better photostabilizer for RP/benzophenone-3 than for RP/avobenzone. The in vitro phototoxicity of the combination RP/avobenzone was reduced by bemotrizinol. Clinical studies did not indicate phototoxic or photoallergenic potentials in all formulations tested. It is concluded that the 3T3 NRU phototoxicity test may be considered a supplementary assay in formulation developments, since it can detect chemically unstable and potentially phototoxic combinations. However, extrapolation of in vitro positive results to human photopatch tests may be performed only to a limited extent.
Assuntos
Dermatite Fotoalérgica/etiologia , Dermatite Fototóxica/etiologia , Fenóis/efeitos adversos , Protetores Solares/efeitos adversos , Triazinas/efeitos adversos , Vitamina A/análogos & derivados , Células 3T3 , Acrilatos/efeitos adversos , Acrilatos/farmacologia , Acrilatos/efeitos da radiação , Adolescente , Adulto , Idoso , Animais , Benzofenonas/efeitos adversos , Benzofenonas/farmacologia , Benzofenonas/efeitos da radiação , Cinamatos/efeitos adversos , Cinamatos/farmacologia , Cinamatos/efeitos da radiação , Diterpenos , Método Duplo-Cego , Interações Medicamentosas , Estabilidade de Medicamentos , Humanos , Camundongos , Pessoa de Meia-Idade , Vermelho Neutro/metabolismo , Fenóis/farmacologia , Fenóis/efeitos da radiação , Ésteres de Retinil , Medição de Risco , Protetores Solares/farmacologia , Protetores Solares/efeitos da radiação , Triazinas/farmacologia , Triazinas/efeitos da radiação , Raios Ultravioleta , Vitamina A/efeitos adversos , Vitamina A/farmacologia , Vitamina A/efeitos da radiação , Adulto JovemRESUMO
Development of photostable sunscreens is extremely important to preserve the UV protective capacity and to prevent the reactive intermediates of photounstable filter substances behaving as photo-oxidants when coming into direct contact with the skin. Thus, the objective of this study was to evaluate the photostability of four different UV filter combinations in a sunscreen by using HPLC analysis and spectrophotometry. The formulations that were investigated included four different UV filter combinations often used in SPF 15 sunscreens. The UV filter combinations were: octyl methoxycinnamate (OMC), benzophenone-3 (BP-3) and octyl salicylate (OS) (formulation 1); OMC, avobenzone (AVB) and 4-methylbenzilidene camphor (MBC) (formulation 2); OMC, BP-3 and octocrylene (OC) (formulation 3); OMC, AVB and OC (formulation 4). In the photostability studies, 40 mg of each formulation were spread onto a glass plate and left to dry before exposure to different UVA/UVB irradiation. Exposed samples were then immersed in isopropanol and the dried film dissolved ultrasonically. The filter components in the resulting solution were quantified by HPLC analysis with detection at 325 nm and by spectrophotometry. In this study, the four UV filter combinations showed different photostability profiles and the best one was formulation 3 (OMC, BP-3 and OC), followed by formulations 4, 1 and 2. In addition, OC improved the photostability of OMC, AVB and BP-3.