Selecting the ALA formulation for optimizing ALA-photodynamic therapy

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

Granada. España.

Congreso; 8th European society for photobiology; 1999

European society for photobiology

The aim of this work was to optimize ALA penetration for its use in photodynamic therapy of skin lesions employing varios vehicle formulatios such as lotion, cream, liposomes, vaseline and DMSO. We have also determined the tissue destribution and kinetics of porphyrin synthesis after topical application of liposomal ALA on a subcutaneously implanted murine adenocarcinoma as well as the effect of DMSO on porphyrin synthesis and ALA penetration through the skin. Tumour porphyrins are synthesized and/or accumulated even in the deepest tumour layers, demonstrating that ALA and/or porphyrins are distributed by microvasculature through the whole tupour, independently of the vehicle employed. ALA lotion alone or with 10% DMSO proved to be most efficient vehicle (1.75 ± 0.25 and 2.09 ± 0.39 mg porphyrins/g tumour respectively), whereas cream and liposomes induced lower levels and identical tetrapyrrole accumulation (0.60 ± 0.18 mg/g). The higher porphyrin production detected upon addition of DMSO to the ALA lotion may be explaneid by three factors :1) Activation of tunour PBGase, which is a regulatory enzyme, 2) higher accumulation of porphyrins in the upper tumour layers due to a higher penetration and/or confinement of ALA, 3) lower efflux from the tumour to the bloodstream.