Oleic acid influence as a cutaneous penetration enhancer for 5- aminolevulinic acid photodynamic therapy of skin cancer: in vitro and in vivo studies in animal model. / Influência do ácido oléico como promotor de absorção cutânea para o ácido 5-aminolevulínico na terapia fotodinâmica do câncer de pele: estudos in vitro e in vivo em modelo animal

AUTOR(ES)

Aline Regina Hellmann Carollo

DATA DE PUBLICAÇÃO

2007

RESUMO

The topical administration of 5-ALA has been distinguished on skin cancer photodynamic therapy (PDT) because of its efficiency in the treatment of tumors and the reduced phototoxic collateral effects. However, this effectiveness is limited by its low penetration in the skin. A proposal to optimize the 5-ALA penetration in the skin is the use of cutaneous penetration enhancers, which seek to alter the cutaneous barrier for many bioactive molecules. The aim of this work was the pharmaceutical development of formulations containing oleic acid (OA) as a cutaneous penetration enhancer, seeking the increase of the cutaneous penetration of 5-ALA for skin cancer PDT. The in vitro flux of 5-ALA from formulations containing OA (10% w/w) was significantly increased after 12 hours of experiment, in comparison with formulations without OA, mainly for the groups containing 5% and 10% of 5-ALA. The stratum corneum (SC) and [epidermis + dermis] without SC retention were also significantly increased, showing an enhancer effect of the fatty acid. In addition, in vivo experiments were accomplished in mice, with the purpose of analyzing the formulation effect on the PpIX production and accumulation in the skin. It was observed that the penetration enhancer s presence significantly increased the amount of PpIX extracted from the skin, in contrast with formulations without this addition. To visualize the PpIX presence in the tissue, confocal microscopy of the treated animal skins was made. The images were suitable with the in vivo experiments, with increased intensity of fluorescence in the tissue samples that were treated with formulations containing OA. Both in vitro and in vivo results showed the potentiality of the formulations containing OA as a cutaneous penetration enhancer for 5-ALA delivery on the skin cancer PDT.

ASSUNTO(S)

câncer de pele photodynamic therapy skin cancer 5-aminolevulinic acid oleic acid terapia fotodinâmica Ácido oléico Ácido 5-aminolevulínico

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