Optimized irradiation regimens for intraperitoneal photodynamic therapy with porphyrin and phthalocyanine photosensitizers are determined in in vitro and in vivo studies. The experimental study on НЕр2 cell line showed that reduce of power density for constant light dose increased significantly the efficacy of photodynamic therapy (the reduce of power density from 20-80 mW/cm 2 to 10 mW/cm 2 had the same results (90% cell death) for half as much concentration of the photosensitizer). The obtained results were confirmed in vivo in mice with grafted tumor S-37. For light dose of 90 J/cm 2 and power density of 25 mW/cm 2 none of animals in the experimental group had total resorption of the tumor. For the same light dose and decrease of power density to 12 mW/cm 2 total tumor resorption was achieved in 34% of animals, 66% of animals died from phototoxic shock. For twofold decrease of light dose – to 45 J/cm 2 with the same low-intensity power density (12 mW/cm 2 ) we managed total tumor resorption in 100% of animals. In the following studies of optimized irradiation regimen for intrapleural photodynamic therapy the reaction of intact peritoneum of rats on photodynamic exposure was assessed and optimized parameters of laser irradiation, which did not cause necrosis and intense inflammatory reaction of peritoneum, were determined – light dose of 10 J/cm 2 with power density of mW/cm 2 . Thus, the reasonability for use of low-intensity regimens of irradiation for intraperitoneal photodynamic therapy was confirmed experimentally with possibility of high efficacy of treatment without inflammatory reactions of peritoneum.
We have experimentally investigated the detoxifying and modifying effects of remaxol in the framework of traditional and high-dose chemotherapy in mice with transplanted tumors. The influence of remaxol in comparison with heptral was studied on the toxic and therapeutic action of cytostatic drugs gemzar, lastet (etoposide), and methotrexate during their traditional and high-dose administration in mice with transplanted P388 lympholeukosis. Remaxol demonstrated a detoxifying action with respect to these cytostatic agents, which decreased in the following series: gemzar lastet methotrexate (according to the results of lethality evaluation). Remaxol significantly increased the therapeutic efficacy of gemzar used in both traditional and high-dose regimes. This was manifested by slowing down tumor growth and increasing animal lifetime during combined administration of the drugs. This may be due to the remaxol potentiation of the antitumor effect of gemzar. In combination with lastet and methotrexate, remaxol does not alter their therapeutic efficacy. The detoxifying action of remaxol with respect to these cytostatics is more pronounced than that of heptral.