The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization

Background The optimal vehicle to ensure adequate penetration of 5-aminolae vulinic acid (ALA) for its use in photodynamic therapy (PDT) of skin lesion s has not been determined. Objectives We aimed to study the effects of ALA in various vehicle formulat ions [saline lotion with and without dimethylsulphoside (DMSO), cream, lipo somes and vaseline] after topical application in a murine subcutaneous aden ocarcinoma model. Methods The effect of DMSO on porphyrin synthesis and ALA penetration throu gh the skin was studied by measuring the uptake of C-14 label from ALA. ALA and prophobilinogen accumulation, and some haem enzyme activities. The tis sue distribution and kinetics of porphyrin synthesis after topical applicat ion 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 for tumour porphyrin accumulation (mean +/- SD 1 . 75 +/ - 0 . 25 and 2 . 09 +/- 0 . 39 mu g g(-1), respectively), whereas cream and liposomes induced lower levels and identical porphyrin accumulation (0 . 6 0 mu g g(-1)). Using ALA + DMSO saline lotion, a higher porphyrin accumulat ion was found in skin overlying the tumour tissue and in the first 2 mm of tumour, probably due to increased ALA penetration, or greater interconversi on to porphyrins, or greater retention of ALA and/or porphyrins. Conclusions These findings reinforce the importance of the vehicle in topic al ALA-based PDT, and explain the mechanism of action of DMSO in enhancing protoporphyrin IX biosynthesis in superficial lesions.