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].
Prerequisites for the use of photodynamic therapy (PDT) to treatment of atherosclerosis, as well as the development and structure of atherosclerotic vascular lesions in humans are analyzed. The basic requirements for PDT components, specifically photosensitizers (PS), and the radiation source, and the current state of their development are overviewed. Some original results of in vitro studies of the effect of PS on the basis of phthalocyanines and radiation on cells from the atherosclerotic plaques are presented.
The paper outlines the role of such innovations as standardization and quality assurance in forensic operations conducted on the territory of the Commonwealth of Independent States (CIS). Rationales are provided for pathways towards standardization of forensic practice as a means of improving the efficiency of forensic contribution to the due process of law by resolving issues that require special knowledge. The authors examine different approaches to the understanding of quality in forensic practice and offer a definition that reflects the hierarchically structured system of law enforcement and courts' forensic needs.
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