Topical 5-aminolevulinic acid for photodynamic therapy of basal cell carcinoma. Evaluation of stratum corneum permeability in vitro

• Published in: Journal of controlled release 1996-12, Vol.42 (3), p.203-208
• Main Authors: Bretschko, Eleonor, Szeimies, Rolf-Markus, Landthaler, Michael, Lee, Geoffrey
• Format: Article
• Language: English
• Subjects: 5-Aminolevulinic acid; Basal cell carcinoma; Biological and medical sciences; Medical sciences; Miscellaneous; Pharmacology. Drug treatments; Stratum corneum
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/0168-3659(96)01338-7

5-aminolevulinic acid (ALA) is used as a protoporphyrin-IX-precursor for photodynamic therapy of superficial skin cancer and cutaneous metastases of internal malignancies. Attempts to give ALA topically - and avoid unpleasant cutaneous photosensitisation - have failed to produce measurable quantities within intact epidermis overlying tumors, in particular for deeper epidermal and subepidermal tumors. In this study, the permeation properties of ALA through excised intact human stratum corneum were examined to determine realistic application times for clinical use. ALA shows the typical behaviour of highly polar solutes. Substantial 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% ALA-loading was developed, which gives rapid release of ALA. Combined release/permeation experiments show a lag phase of ∼20 h, after which a flux of ∼0.5 μg ALA/cm 2/h is achieved. The topical application of ALA from a thin film for photodynamic therapy is, therefore, feasible, even when there is intact stratum corneum at the tumor site.