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The use of liposomes as drug delivery systems today is a recognized approach to improving the effectiveness of treatment. Compared with other nanosized carriers, liposomes are highly biocompatible. However, in the literature, there are a number of data on the immunogenicity of some liposomal drugs. Hypersensitivity reactions of moderate to severe severity were noted in some patients with intravenous administration of liposomes Doxil®, Ambisome®, DaunoХome®. The technology of production of liposomes is a laborious process and obtaining liposomal forms on an industrial scale is problematic for researchers and manufacturers around the world. In connection with this, studies on the scaling up of technology for obtaining liposomes and studying the specific toxicity of liposomal preparations are relevant. Objective – evaluation of the quality of prototypes of liposomal dosage form based on tetra-3-phenylthiophthalocyanine hydroxyaluminum obtained by scaled technology in comparison with samples produced in laboratory conditions, as well as studying their mutagenic and immunotoxic properties. Object of the study – tetra-3-phenylthiophthalocyanine hydroxyaluminum liposomal, lyophilizate for the preparation of injection for injection of 1,5 mg, in bottles with a capacity of 20 ml (LLF). Materials and methods. Bengem’s method, extrusion, sterilizing filtration, lyophilization, intercellular contact integrity test (for promoter activity), Ames bacterial test, cytogenetic study of chromosomal aberrations, DNA damage test (DNA comet test), Erne method; hypersensitivity reaction of delayed type, determination of mass and cellness of central and peripheral immunity organs, evaluation of phagocytic activity of peritoneal macrophages. Results. Based on the results of the research, the LLF production technology is scaled, which allows obtaining up to 400 LLF flasks per production cycle. It has been established that LLF at doses of 6 and 24 mg/kg does not cause an increase in the number of chromosomal abnormalities in mice and does not cause DNA damage, in doses of 1,1–22,0 μg/dish LLF does not show mutagenic activity in the Ames bacterial test, in the range concentrations of 0,062–3,1 μg in the test for promoter activity does not separate intercellular contacts. It is determined that in doses of 6 and 12 mg/kg, LLF does not affect humoral and cellular immunity, does not change the mass and cellularity of the central and peripheral organs of the immune system. LLF, 24 hours after administration at doses of 6 and 12 mg/kg, dose-dependently decreases the phagocytic activity of peritoneal macrophages, which is restored after 7 days. Conclusion. The technology of LLF production is scaled. In the doses studied, it was found that LLF does not have the ability to promote the process of carcinogenesis and the lack of influence on the humoral and cellular immune response.

Introduction. Glucocorticoids are the important component of combined chemotherapy of blood cancer. Therapeutic effects of glucocorticoids is realized via activation of glucocorticoid receptor transrepression, the development of side effects is associated with transactivation. We demonstrated earlier that compound belonging the class of selective glucocorticoid receptor agonists, CpdA, selectively induced transrepression in blood cancer cells. CpdA represents a mixture of two enantiomers, which can differ in interaction with the receptor. Aim. The main aim of present study was to synthesize CpdA enantiomers and to evaluate their biological properties. Materials and methods. Synthesis was carried out based on Sharpless dihydroxylation; anti-tumor activity in vitro was evaluated by antiproliferative and pro-apoptotic effects. Ligand properties were estimated by PCR-analysis of glucocorticoid- and NF-kB-dependent genes expression. Results and conclusions. We demonstrated that CpdA enantiomers revealed anti-tumor activity in vitro and did not induce transactivation. Moreover, S-enantiomer of CpdA in the most tests demonstrated more pronounced activity and is more perspective molecule for future studies in vivo.

Hematological disorders include a wide spectrum of malignancies of hematopoietic and lymphoid tissues. The genetic changes underlying the pathogenesis of the diseases are specific for each disease. High incidence of chromosomal aberrations (deletion, translocation, insertion) is one of the principal characteristics of oncohematological diseases. In addition, mutations in individual genes or blocking of normal regulation of gene functioning in relation to epigenetic events can occur. Progression of oncohematological diseases could be a result of accumulation of different genetic abnormalities. Modern classification of malignancies of hematopoietic and lymphoid tissues is based on the analysis of clinical data, morphological and functional characteristics of tumor cells and identification of specific cytogenetic and molecular-genetic changes. A large number of genetic abnormalities specific for certain types of hematological malignancies has been discovered to date. It allows to optimize the treatment strategy, as well as to design, test and introduce to the clinical practice a number of targeted drugs (inhibitors of chimeric proteins formed as a result of trans-locations and triggering the malignant cell transformation). Drugs based on monoclonal antibodies (Rituximab, Alemtuzumab, etc.) or low molecular weight compounds (Imatinib, Bortezomib, Carfilzomib) form this group of medications. The knowledge about not only specific gene abnormalities but also about the corresponding changes in cell efferent signaling pathways could be of great interest for the development of new targeted molecules or the repurposing of known chemotherapeutic agents. The present review compares genetic aberrations in diseases listed in the 2008 WHO classification (amended in 2016) of hematopoietic and lymphoid tissue malignancies and main changes in cell signaling pathways associated with malignant transformation of hematopoietic cells.