Introduction. Special attention has been recently paid to photosensitizers that absorb and fluoresce in the near infrared region of the spectrum. One of the most promising photosensitizers is bacteriosens, a synthetic bacteriochlorin derivative. Objective. To conduct a preclinical study of the biodistribution and pharmacokinetics of bacteriosens in animals.Materials and methods. The active ingredient of bacteriosens is (meso-tetra(3-pyridyl)bacteriochlorin) with of λmax 747 nm). The biodistribution and pharmacokinetics of the agent were studied in mice and rabbits. It was administered intravenously once at three doses: 1.0; 2.5 and 6.25 mg/kg for the mice and 0.236; 0.59 and 1.475 mg/kg for the rabbits. Local fluorescence spectroscopy was used for the quantitative determination of the pharmacokinetic parameters of bacteriosens.Results. Bacteriosens was removed quickly from the mouse bloodstream at 1 and 4 days after using minimal (1.0 mg/kg) and maximal (6.25 mg/kg) doses, respectively. When given at doses of 6.25 mg/kg and 1.0 mg/kg, bacteriosens was recorded in the skin, muscle, and spleen for 4 days and 24 h, respectively. The agent most intensively accumulated and long persisted in the omentum, liver, and kidneys for more than 6 days (6.25 mg/kg) and 2 days (1.0 mg/kg). A similar pattern was observed in the rabbits. Bacteriosens was rapidly removed from the rabbit bloodstream at 1 and 3 days after using at doses of 0.236 and 1.475 mg/kg, respectively. The agent was recorded in the skin, muscle, and spleen up to 4 days (1.475 mg/kg) and 3 days (0.236 mg/kg). It most intensively accumulated and long persisted in the omentum, liver, and kidneys for more than 6 days (1.475 mg/kg) and 4 days (0.236 mg/kg).Conclusion. Bacteriosens was removed from the animal bloodstream within 3–4 days after administration of the maximum dose that was 2.5 times higher than therapeutic one. The half-life of bacteriosens for mice was directly proportional to the dose and increased from 8 to 24 min; the half-life for rabbits was 20 min, irrespective of the dose. The drug was recorded in the skin for no more than 4 days. The main routes of bacteriosens elimination from the body of animals were the kidneys and liver.The study was performed in accordance with ethical principles adopted by the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes.

Purpose of the study. The objectives of the research are to evaluate the potential toxicity of Bacteriosens when administered to animals once only («acute» toxicity) or repeatedly («chronic» toxicity) and to study its biocompatibility with blood components.Materials and methods. Bacteriosens is the medicine on the basis of photoactive compound of mezo-tetra (3-pyridyl) bacteriochlorin with λmax of 747 nm. Ex vivo study of its biocompatibility with blood components included the evaluation of the impact of the solution on the coagulability of non-stabilized venous blood. The in vitro method of detecting erythrocyte osmotic resistance to hemolytic ability of Bacteriosens was used. The «acute» toxicity was studied in F1 hybrid mice (CBA x C57Bl/6j) and non-bred rats, male and female, after single intravenous and intraperitoneal injections of Bacteriosens. The «chronic» toxicity was studied in non-bred rats, male and female, and Soviet Chinchilla rabbits after multiple intravenous injection of the drug (over the period of 14 days). Time period before toxicity-induced death of animals, clinical signs of intoxication, and the impact of the medicine on the inner organs and body systems were evaluated using physiologic and pathophysiologic, clinical, and laboratory methods.Results. Incompatibility of non-stabilized rat blood with Bacteriosens after the incubation with the medicine in concentrations varying from 0.5 till 0.005 mg/ml has not been discovered. The aquatic solution of Bacteriosens should be injected into animals and later on into humans slowly or by drip feed in concentrations not exceeding 0.5 mg/ml. A single injection of Bacteriosens in doses from 5.0 to 50.0 mg/kg and from 1.3 to 20.8 mg/kg to mice and rats (male and female), respectively, was tolerated by the animals satisfactorily. No toxicity-induced deaths or skin phototoxicity have been detected. The studied doses of Bacteriosens in mice 25-250 times exceeded the calculated equitherapeutic dose for humans, and in rats, 6.5-104 times. Bacteriosens in total doses from 18.2 to 72.8 mg/kg and from 8.3 to 33 mg/kg administered as multiple intravenous injections for 14 days to rats and rabbits respectively, did not induce the death of the animals and demonstrated no toxic impact on blood, liver, kidneys, heart, hemostasis system, or central nervous system. The drug did not adversely affect carbohydrate and lipid metabolism.Conclusion. Bacteriosens when administered as a single dose or as multiple injections in the range of studied doses did not have adverse toxic effect on mice, rats, and rabbits. The studied doses of Bacteriosens in rats 91-364 times exceeded the calculated equitherapeutic dose for humans, and 41-165 times, in rabbits.

Introduction.Bacteriochlorins are the most promising photosensitizers absorbing in the near-infrared spectral region. Their use can enhance the efficiency of photodynamic therapy due to the deeper penetration of radiation into the tumor.Objectiveto conduct a preclinical study of the photoinduced antitumor activity and biodistribution of Bacteriosens.Materials and methods.Bacteriosens is a preparation based on meso-tetra(3-pyridyl)bacteriochlorin absorbing at 747 nm. Photoinduced cytotoxicity was investigated in vitro using human tumor cells: A549, Hep 2, BT-474, MCF-7, SK-BR-3, PC3, and EJ and murine tumor cells: S37, C26, and LLC. In vivo studies were performed in mice with large and small tumors (S37, LLC, and C26).Results.In vitro investigation show that bacteriosens during optical irradiation led to the effective suppression of tumor cell growth in culture (the IC50 value varied from 0,08μМ to 1,21 μМ) and had no toxicity without exposure to light. The effective photodynamic therapy regimen using Bacteriosens in mice with inoculated small and large tumors of different genesis resulted in regression of a primary tumor node on 90–100 % of the animals in the absence of tumor recurrence within 90 days after treatment.Conclusion.Bacteriosens is a promising agent for the photodynamic therapy of small and large tumors; it can be successfully used as an alternative, organ-sparing minimally invasive treatment for malignant tumors, including prostate cancer.