Photosensitizers for photodynamic therapy of cutaneous disease.

Photodynamic therapy is a rapidly developing treatment modality in dermatology. A sensitizer drug is activated by light in the presence of oxygen. This results in the release of reactive oxygen species that damage the target tissue. The ideal features of a photosensitizer are that it should be highly selective for lesional tissue, activated by light of a sufficiently long wavelength for tissue penetration, and have a high photodynamic yield (i.e. production of singlet oxygen). A short time interval between administration and its maximal accumulation in tumour tissue, followed by rapid tissue clearance, are also desirable. First-generation sensitizers were complex chemical mixtures, needing parenteral administration and causing troublesome and prolonged photosensitivity. A range of second-generation sensitizers of different chemical families show several advantages including purity, longer activation wavelength and less prolonged photosensitivity, but effective topical formulations have not been developed. Currently, the most convenient and widely practised form of PDT for cutaneous disorders is the topical application of the pro-drug delta-aminolevulinic acid or its methylated ester, which are activated by light following metabolism to the endogenous sensitizer protoporphyrin IX.