K. Kassab¹, G. Jori¹, C. Fabris¹, E. Reddi¹, G. Roncucci², D.Dei², M.P. De Filippis²

Although systemically administered porphyrin-based photosensitizers have been used in the treatment of many non-oncological and oncological skin diseases such as psoriasis, actinic keratosis and non melanoma skin cancers, yet prolonged general skin photosensitivity which persists for many weeks with the risk of severe accidental phototoxic reactions is a major disadvantage of this form of therapy.

Topical PDT utilizing a variety of sensitizers could bypass this unwanted effect. Thus,the topical application of ALA and HpD followed by visible light irradiation has shown good response rates in the treatment of solar keratosis, verrucae vulgaris, psoriasis and some other superficial skin cancers. In addition, the second generation photosensitizer zinc-phthalocyanine showed to be a promising agent in the treatment of hyperproliferative skin conditions.

With the aim to define the efficiency of second generation photosensitizers in topical PDT, a series of newly synthesized phthalocyanine derivatives were tested for:

1. Photostability after different intervals of irradiation with a diode laser at 675nm.
2. Photooxidative efficiency towards biological macromolecules such as aminoacids (tryptophan or N-acetyltryptophanamide).

In addition, in vivo studies were carried out involving detailed pharmacokinetics of one selected phthalocyanine in skin, serum, and liver as a function of time and topically applied dose. On the basis of the information thus obtained, topical PDT studies have been fulfilled with the aim to define the minimal erythemal dose (MED) (fluence rate and total light fluence). Ultrastructural as well as optical microscopy techniques were used to identify the subcellular targets during PDT as well as the depth and mechanism of photodamage.