Topical Administration of Tetrasodium-Mesotetraphenyl-Porphinesulfonate (TPPS): Correlation between Drug Penetration and Depth of Necrosis in Skin of Nude Mice following Red Light Irradiation

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Abstract
The main side effect in photodynamic therapy is photosensitization of the patient's skin following systemic administration of the photosensitizing agent. In the case of superficial lesions, this problem can be avoided by topically applying the drug: in this way a local treatment can be performed. We tested the photosensitizing properties of a 2 % solution of TPPS (tetrasodium-tetraphenylporphinesulfonate) in a vehicle containing a penetration enhancer, Azone, on skin of nude mice. An aliquot of 0.1 ml/cm2 of the solution was painted on the skin overlying an s.c. implanted NMU-1 tumor. Subsequently, animals were sacrificed at different times after application. Fluorescence microscopy revealed that TPPS penetration depth was related to time elapsed after application and to painting modalities. Solution penetration was enhanced by wiping with ether immediately before painting. Irradiation at 80 mW/cm2 for 20 min with a dye laser emitting at 640 am, 4 h after TPPS application, produced necrosis of the upper skin layers, up to 0.2 mm in depth. These findings suggest that topical TPPS administration, followed by laser irradiation, may be a suitable treatment modality for skin lesions involving epithelial layers, even though several aspects of this metodology need further investigation.