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

CASAS A, FUKUDA H, DI VENOSA G, BATLLE A

Londres, Inglaterra

Workshop; Tetrapyrrole Discussion Group; 1999

Tetrapyrrole Discussion Group

The optimal vehicle to ensure adequate penetration of 5-aminolevulinic acid (ALA) for its use in photodynamic therapy (PDT) of skin lesions has not been determinated. We aimed to study the effects of ALA in various vehicle formulations after topical application in a murine subcutaneous adenocarcinoma model. The effects of DMSO on porphyrin synthesis and ALA penetration through the skin was studied by measuring of 14C label fron ALA. ALA and porphobilinogen accumulation and some haem enzyme activities. The tissue distribution and kinetics of porphyrin synthesis after topical application of ALA entrapped in large multilamellar liposomes was also determinated. ALA in saline lotion, alone or with 10% DMSO proved to be the most efficient vehicle for tumour porphyrin accumulation, whereas cream and liposomes induced lower levels and identical porphyrin accumulation. Using ALA+DMSO saline lotion, a higher porphyrin accumulation was found in skin overlaying the tumour tissue and in the first 2 mm of tumour, probably due to increased ALA penetration, or greater retenetion of ALA and/or porphyrins. These findings reinforce the importance of the vehicle in topical ALA-based PDT, and explain the mecanism of action of DMSO in enhancing protoporphyrin IX biosynthesis in superficial lesions.