The photodynamic activity and pharmacokinetics of a new liposomal form (LF) of the sensitizer Photosense based on aluminum sulfophthalocyanine salts have been studied in comparison to those of the standard form (SF) representing a 0.2% aqueous solution of the parent substance. The effective therapeutic doze of the LF of Photosense in mice bearing Ehrlich's tumor was 1 mg/kg, which is four times as small as the effective dose of the SF. The selectivity of accumulation in the tumor tissue 24 h after administration for the LF of Photosense was 1.5 times higher than for the SF. The drug accumulation in skin (determined by the fluorescence intensity) on the 7th days of experiment for the LF of Photosense was 1.6 times lower than for the SF. The pharmacokinetics of the LF of Photosense in mice without tumors significantly differs from the behavior of the SF.In recent years, the photodynamic therapy (PDT) and fluorescent diagnostics (FLD) of neoplasms have been extensively developed both in the experimental oncology and on the clinical level. In Russia, several potential photosensitizers for PDT and FLD are currently under clinical investigation [1 -4]. Among these, most thoroughly studied is Photosense -a domestic photosensitizer of the second generation -representing a mixture of sodium salts of sulfonated aluminum phthalocyanine, which is synthesized using an original patented technology developed at the State Research Institute of Organic Semiproducts and Dyes (Moscow) [5,6].Previous investigations into the mechanisms of the photodynamic damage of inoculated tumors by Photosense showed that the therapeutic activity of this drug is a multifactor process including (i) necrosis and apoptosis of tumor cells under the direct action of cytotoxic agents (singlet oxygen, free radicals) generated in the course of PDT and (ii) ischemic necrosis caused by the violated blood flow in vessels of the tumor [7]. The results of pathomorphological investigations [7] showed that the direct photodynamic effect of Photosense on the cells and tissues of parenchyma was more pronounced when the period of time between the photosensitizer administration and irradiation exceeds 24 h. The active components of Photosense have various degrees of sulfonation and, hence, differently penetrate through vessel walls and influence the parenchyma [8,9]. The amphiphilic character of the photosensitizer also significantly influences the ability of Photosense to penetrate through the membranes of tumor cells. The attachment of two biotin residues to the molecule of Photosense provided for nearly optimum amphiphilic properties and significantly increased the efficacy of the drug action [10].

Background. In connection with the prospect of the use of an analog of the hypothalamic hormone somatostatin synthesized by the laboratory of chemical synthesis Institute of experimental diagnostics and chemotherapy of FSBI «N.N. Blokhin Russian Cancer Research Center» and showed a high anti-tumor activity as a drug arises a need to establish an optimal technology of its receipt. In preliminary studies in a modelformulation for an analog of the hypothalamic hormone somatostatin selected liposome technological process of which has a series of specific steps comprising. Objective. Development of technology for obtaining liposomal formulation hypothalamic hormone somatostatin analogue. Materials and methods. Liposomes analog of the hypothalamic hormone somatostatin obtained by method Bengema in modification for hydrophobic substances. To reduce the diameter of the liposome are used methods extrusion, homogenization and ultrasonic. Analysis of the size of the liposomes was performed by correlation spectroscopy light scattering using nanosizer. The pH of the liposomal dispersion was determined by potentiometry. The quantitative content of the drug substance was determined by spectrophotometry using a standard sample with X (282 ± 3) nm and an alcoholic solution of empty liposomes as a reference solution. Amount of incorporated drug was calculated as the ratio of the concentration of drug in the liposome dispersion after filtration to the concentration of drug in the dispersion after preparation. Results and Conclusion. The hydrophobic nature of the substance causes an analog of the hypothalamic hormone somatostatin technological features of obtaining liposomal formulation. Since the step of forming a film of the lipid substance is dissolved in an organic solvent together with lipids, film is hydrated by a solution of cryoprotectant. Grinding liposomes an analog of the hypothalamic hormone somatostatin appropriate to be carried out using homogenization or extrusion methods, due to the high efficiency of these methods, the preservation stability of the liposomes and a high percentage of inclusion an analog of the hypothalamic hormone somatostatin, included in the liposomal bilayer. At the stage of separating the non-inclusion of substance an analog of the hypothalamic hormone somatostatin due to the insolubility of the substance in the water, you can use the filtering method, without the need for complicated procedures gel filtration, dialysis, etc. Furthermore the process of separating a substance not included can be combined with the sterilization of the liposome dispersion by selecting a particular filter material.

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The optimum composition of temperature-sensitive liposomes (TSLs) has been chosen and a method of doxorubicin loading in TSLs by ammonium ion gradient has been developed. The TSL-encapsulated doxorubicin was lyophilized for better stabilization with 4.0% sucrose added as a cryoprotective agent. A method based on spectrophotometry at 252 nm is proposed for the determination of oxorubicin concentration in TSLs. It is established that TSLs encapsulate 89.5 ± 3.5% of doxorubicin. The particle size of the vesicles is 165 ± 10 nm. The proposed TSL doxorubicin formulation possesses selective action, shows higher efficiency and lower toxicity in comparison to the traditional doxorubicin, and can be recommended for use in the chemo-thermotherapy of solid tumors.

Despite the rapid development of medical technologies, chemotherapy treatment still occupies an important place in clinical oncology. In this regard, the current research in this area focuses on the synthesis of new highly effective antitumor substances that have minimal side effects and the development of stable pharmaceutical formulations (PF) on their basis. In order to solve this problem, the I. Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences actively sought for original substances, namely, nitrosourea (NU) derivatives, one of the most promising classes of anticancer drugs. As a result of this research, a novel NU derivative was synthesized, namely ormustine, which showed high antitumor activity in preliminary preclinical trials. It is now crucial to develop an ormustine pharmaceutical formulation. Conducted technological studies showed that the most suitable solvent for the drug substance is 0.1 M hydrochloric acid, which ensures its rapid dissolution by ultrasonic treatment. A significant reduction in the concentration of the active ingredient during the storage of the solution required the development of a technique of its lyophilization and the selection of a shaper such as a Kollidon 17 PF. Upon completion of the development of a pharmaceutical formulation of ormustine, its stability after lyophilization was demonstrated, and a sufficient amount of the drug has been acquired for preclinical research.