A vehicle for photodynamic therapy of skin cancer: influence of dimethylsulphoxide on 5-aminolevulinic acid in vitro cutaneous permeation and in vivoprotoporphyrin IX accumulation determined by confocal microscopy

Topical application of 5-aminolevulinic acid (5-ALA) followed by light irra diation is a new concept of photodynamic therapy (PDT) of skin cancers. 5-A LA is a prodrug that can be converted by the heme biosynthetic pathway into protoporphyrin IX, an effective photosensitizer. In the present work we pr opose the enhancement of 5-ALA-induced protoporphyrin IX accumulation by di methylsulphoxide (DMSO) and ethylenediamine-tetraacetic acid disodium salt (EDTA). The presence of 20% DMSO (w/w) in oil-in-water emulsions increased the in vitro permeation of 5-ALA through hairless mouse skin. In vivo studi es demonstrated a significant increase in the amount of protoporphyrin IX e xtracted from healthy hairless mouse skin after 3 h treatment with an oil-i n-water emulsion containing 10% 5-ALA (w/w), 3% EDTA (w/w) and 20% DMSO (w/ w), By confocal scanning laser microscopy imaging, an observed increase in red fluorescence, at 476 nm excitation and emission detected longer than 59 0 nm, in skin that had received this treatment, was attributed to protoporp hyrin IX accumulation. Although no effect of EDTA on short-term protoporphy rin IX accumulation in skin was detected, this chelator could protect 5-ALA from decomposition during prolonged topical administration. The results ob tained indicate that association of 5-ALA, EDTA and 20% DMSO may enhance th e delivery of 5-ALA to the skin in the topical PDT. (C) 2000 Elsevier Scien ce B.V. All rights reserved.