Evaluation of the influence of iontophoresis on the penetration and distribution of a photosensitizing agent in hydrophilic skin cancer for topical photodynamic therapy

Abstract

Topical photodynamic therapy is a novel therapeutic modality for the treatment of skin tumors. Research in this area are directed to the study of photosensitizing agents and delivery systems to increase its penetration and location in the target tissue. The phthalocyanines have been identified with potential systemic photosensitizers due to, among other advantages, its high affinity for tumor tissue and its marked effect when under light irradiation. However, the high lipid solubility and low partition coefficient oil / water these substances hinder its diffusion in the stratum corneum (EC), the main barrier to skin penetration of drugs into the layers of the skin where the skin tumors are located. Full of phthalocyanines derivatives, such as zinc tetrasulfonated anion (ZnPcS4) have been synthesized in an attempt to increase its solubility in water, as well as change / improve its uptake by tumor cells.owever, non-charged molecules can not even penetrate the EC. Iontophoresis is a noninvasive technique able to increase and control the penetration of large molecules and loaded on the skin by applying an electrical current of low intensity. The application of iontophoresis as a delivery system for hydrophilic derivatives of phthalocyanines appears to be an alternative to topical administration of photosensitizing agents for the treatment of skin tumors by PDT. In fact, our group found that iontophoresis significantly increases the penetration of ZnPcS4 in the viable epidermis. These studies have been done, however, healthy skin. In this study, the penetration of the skin and intratumoral ZnPcS4 be directly evaluated in vivo in tumors of squamous cell carcinoma induced in immunosuppressed mice after application of iontophoresis. The confocal laser scanning will be used to investigate the distribution of fluorescent drug in the tumor after treatment. In a second step, the treated tumors will undergo PDT and tumor regression evaluated. It is expected that the application of iontophoresis to increase the penetration and improve the distribution of ZnPcS4 the tumor, making topical PDT with this drug more promising.