TOPICAL 5-AMINOLEVULINIC ACID FOR PHOTODYNAMIC THERAPY OF BASAL-CELL CARCINOMA - EVALUATION OF STRATUM-CORNEUM PERMEABILITY IN-VITRO

5-aminolevulinic acid (ALA) is used as a protoporphyrin-IX-precursor f or photodynamic therapy of superficial skin cancer and cutaneous metas tases of internal malignancies. Attempts to give ALA topically - and a void unpleasant cutaneous photosensitisation - have failed to produce measurable quantities within intact epidermis overlying tumors, in par ticular for deeper epidermal and subepidermal tumors. In this study, t he permeation properties of ALA through excised intact human stratum c orneum were examined to determine realistic application times for clin ical use. ALA shows the typical behaviour of highly polar solutes. Sub stantial amounts pass the SC during the lag phase, but permeability is low (10(-5)-10(-4) cm/h). A thin film of Eudragit RL 100 having 5% AL A-loading was developed, which gives rapid release of ALA. Combined re lease/permeation experiments show a lag phase of similar to 20 h, afte r which a flux of similar to 0.5 mu g ALA/cm(2)/h is achieved. The top ical application of ALA from a thin film for photodynamic therapy is, therefore, feasible, even when there is intact stratum corneum at the tumor site.