The influence of the vehicle on the synthesis of porphyrins after topical application of ALA

ADRIANA GABRIELA CASAS; FUKUDA, HAYDÉE; DIVENOSA, GABRIELA; BATLLE, ALCIRA MARÍA DEL CARMEN

British Journal of Dermatology

Lugar: Londres; Año: 2000 vol. 143 p. 564 - 572

Background The optimal vehicle to ensure adequate penetration of 5-aminolaevulinic acid (ALA) forits use in photodynamic therapy (PDT) of skin lesions has not been determined.Objectives We aimed to study the effects of ALA in various vehicle formulations [saline lotion withand without dimethylsulphoxide (DMSO), cream, liposomes and vaseline] after topical application ina murine subcutaneous adenocarcinoma model.Methods The effect of DMSO on porphyrin synthesis and ALA penetration through the skin wasstudied by measuring the uptake of 14C label from ALA, ALA and porphobilinogen accumulation,and some haem enzyme activities. The tissue distribution and kinetics of porphyrin synthesis aftertopical application of ALA entrapped in large multilamellar liposomes was also determined.Results ALA in saline lotion, alone or with 10% DMSO, proved to be the most efficient vehicle fortumour porphyrin accumulation (mean +/- SD 1.75 +/- 0.25 and 2.09 +/- 0.39 ug/g, respectively),whereas cream and liposomes induced lower levels and identical porphyrin accumulation(0.60 ug/g). Using ALA 1 DMSO saline lotion, a higher porphyrin accumulation was found inskin overlying the tumour tissue and in the first 2 mm of tumour, probably due to increased ALApenetration, or greater interconversion to porphyrins, or greater retention of ALA and/orporphyrins.Conclusions These findings reinforce the importance of the vehicle in topical ALA-based PDT, andexplain the mechanism of action of DMSO in enhancing protoporphyrin IX biosynthesis insuperficial lesions.