Pharmacokinetic and phototherapeutic studies of monocationic methoxyphenylporphyrin derivative

Background and objetive: Photodynamic therapy, a novel treatment for cancer, works through photoactivation of a tumor-localized photosensitive drug, and localized through oxidative damage to kill cells and ablate tumors. Pharmacokinetic and phototherapeutic properties of a cationic porphyrin were assayed in a Balb/c mouse cancer model in order to evaluate its efficiency as photosensitizer. Methods: Biodistribution studies were carried out by intraperitoneal injection of 5 mg/kg CP incorporated into a liposome solution. CP was recovered from serum and organs at various times after treatment. The serum biochemical parameters and histological studies were used to test hepatic and renal functionality. For phototherapeutic studies, the light source used was a slide projector (360 J/cm(2)). The efficiency of CP was evaluated by following tumor growth curves for 10 days after PDT doses. Immunohistochemical detection was carried out to evaluate caspase-3 activation in CP-PDT-treated tumors. Results and conclusions: The photosensitizer distribution suggests that CP is mainly eliminated from the organism via the bile-gut pathway, and that neurotoxic and cutaneous photosensitivity effects are reduced or absent. The porphyrin distribution from bloodstream to tissue began at 24 h of drug administration. CP did not affect the hepatic and renal functionality, as was demonstrated by the physiological parameters. PDT-treated tumors showed delay in growth rate as compared to untreated control mice. Biochemical studies showed that the efficient tumor regression is dependent on caspase-3 activity signaling response associated with apoptosis. The results obtained suggest that the porphyrin CP may be a promising candidate for further use in PDT treatments. (c) 2004 Elsevier B.V. All rights reserved.