RESUMO
BACKGROUND AND OBJECTIVES: (Pre)cancerous skin lesions accumulate more protoporphyrin IX (PpIX) upon topical application of 5-aminolevulinic acid (ALA) than the surrounding normal skin. This might be the result of a higher percutaneous penetration of ALA into (pre)cancerous skin. STUDY DESIGN/MATERIALS AND METHODS: ALA penetration through (1) healthy skin with intact stratum corneum, (2) healthy skin with reduced stratum corneum (i.e. tape stripped skin) and (3) diseased skin with dysplastic and thickened epidermis (chronically UVB-exposed skin) was determined in an in vitro model with hairless mouse skin. RESULTS: More ALA had penetrated through chronically UVB-exposed skin than through normal non-exposed skin after 8 hours ALA application. The amount of ALA penetrated through chronically UVB-exposed skin was smaller than through tape stripped skin. CONCLUSIONS: The stratum corneum barrier function is less effective in chronically UVB-exposed skin than in normal non-exposed skin, but more effective than in tape stripped skin. A higher penetration rate of ALA into (pre)cancerous lesions may be (partly) responsible for the greater accumulation of PpIX in such lesions.
Assuntos
Ácido Aminolevulínico/farmacocinética , Fármacos Fotossensibilizantes/farmacocinética , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Animais , Modelos Animais de Doenças , Feminino , Técnicas In Vitro , Camundongos , Camundongos Pelados , Neoplasias Induzidas por Radiação/etiologia , Lesões Pré-Cancerosas/metabolismo , Neoplasias Cutâneas/etiologiaRESUMO
BACKGROUND AND OBJECTIVES: ALA esters have been developed to improve PpIX production in ALA-PDT, but they do not perform as well in skin as they do in cells and the bladder. STUDY DESIGN/MATERIALS AND METHODS: The in vitro penetration across normal mouse skin of ALA and its methyl and hexyl ester was determined for different application concentrations. ALA and the esters were also applied to tape stripped skin to determine the effect of the stratum corneum. RESULTS: The penetration of ALA and the esters was higher through tape stripped skin than through normal skin (P < 0.01), showing that the stratum corneum is an important barrier. The experiments with different application concentrations indicated that the skin penetration through normal skin and tape stripped skin is highest for ALA and lowest for the hexyl ester. CONCLUSIONS: The differences in skin penetration properties could be (co-)responsible for the finding that ALA esters do not induce substantially higher PpIX levels in in vivo skin.
