Vol 15, No 2 (2016)

Target delivery of antitumor drugs to cancer cells seems to be the very promising way of cancer therapy. The study on the application of immunoliposomes as nanocontainers for anticancer drugs started in the 90-ies. Immunoliposomal drug formulations of antitumor preparations have some advantages over traditional forms of drugs: lipid capsule reduces toxicity of drug due to the selective delivery to tumor and improves its bioavailability. However, despite these benefits, at present immunoliposomal drugs application is limited in the clinic. This review discusses current research status in field of development immunoliposomes and the possible targets for anticancer immuno-liposomes.

Background. Class III beta-tubulin (TUBB3) is one of the eight beta tubulin isotypes identified in human. It is constitutively expressed in brain and testis but not in lung tissue. TUBB3 is also known to appear in solid tumors, in particular in non-small cell lung cancer (NSCLC), and it is often associated with poor prognosis and resistance to taxanes and Vinka alkaloids. Objective: We have suggested that TUBB3 expression may cover not only the primary tumor but also a wide adjacent area of morphologically normal lung tissue. To check the hypothesis we have measured TUBB3 expression both in the non-small cell lung carcinoma (NSCLC) and remote lung tissue derived from the same lung. 60surgical biopsy specimens of NSCLC and morphologically normal lung tissue of 30patients were investigated. Materials and methods. Biopsy specimens were converted to suspension, fixed in 4 % formaldehyde and analyzed by flow cytometry using monoclonal antibodies to TUBB3. The method was developed in the laboratory of medicinal chemistry research Institute of experimental diagnostics and therapy of tumors (N.N. Blokhin Russian Cancer Research Center) and patented. Results. Fraction of TUBB3-positive cells in the group of adjacent lung tissue specimens was lower compared to NSCLC group but still positive in the majority of adjacent lung tissue specimens (25 of 30) and achieved up to 39 % of cells. Conclusion. We suggest that TUBB3 expression in adjacent morphologically normal lung tissue indicates presence of transformed and potentially malignant cells far from the primary site.

Objective: Evaluation of antitumor activity of a novel alkylnitrosoureas derivative Ormustine (an alkylnitrosocarbamoyl L-ornithine) in mouse lymphoid leukemia models. Materials and methods Antitumor activity of Ormustine has been evaluated in B6D2F1 mice with ascites form of leukemia (L1210, L1210/arenosa, L1210/citrullin and P388) and the solid (P388) form. In this study we used preparations from the alkylnitrosourea group: Ormustine, Aranoza and Lizomustine. Treatment of animals was started 24 hours after inoculation of leukemia intraperitoneally, and 48 hours after inoculation subcutaneous P388. Drugs in a wide range of doses were administrated once intravenously. The follow up period of the animals continued until their death. Criteria of antitumor effect were increasing life expectancy and cure. Evaluation criteria of antitumor effect was the increase in life of experimental mice compared to control ones. Results. Antitumor activity of a novel alkylnitrosoureas derivative, Ormustine has been studied in vivo on the growth of transplanted lymphoid leukemia, such as L1210 (ascites version) and P388 (ascites and solid tumor). Effective dose of single intravenous injection Ormustine against lymphoid leukemia L1210 and P388 was 125 mg/kg. The drug effectively inhibited growth of experimental leukemia. The significant part of the mice with limfoleukemia has been cured. We have also established the single intravenous therapeutic dose of Ormustine on L1210 and Р388 leukemia - 125mg/kg of body weight. Conclusion. The data obtained characterizes Ormustin as a promissing anticancer drug.

Background. Present study was dedicated to identification and evaluation of the biologically active components in multiphytoadapto-gene preparation phytomix-40 (PhM-40). It consists of forty plant extracts components including Panax ginseng. PhM-40 demonstrates wide spectrum of biological effects including antimutagenic, antitumor, radioprotective, hormone-modulating, antioxidant, neuropro-tective and ummunomodulating activities. Objective: of this study was to identify and to quantify ginsenosides content in the preparation. Materials and method. Experimental design included the comparison of ginsenosides content evaluation in PhM-40, comparison preparation (which contains similar to PhM-40 plant extracts components but another rations) and Panax ginseng extract by means of LC-MS/MS spectroscopy method. Two different gradients were used: the short and the long ones. By means of the short one rapid compound identification with economical consumption of chemicals was possible as well as the long one allowed us to identify compounds with better resolution capability. Commercially available ginsenosides were the standards for calibration. Literature data were also used for ginsenosides identification. Results. High through liquid chromatography method with tandem mass-spectrometry was successfully used for ginsenosides identification quantitatively and qualitatively in plant preparation PhM-40. The data obtained show the ginsenosides qualitative composition which has been identified as Rb, Rb₂, Rc, Rd, Rg_p Rg₂, Re, Rf, Ro, malonyl-Rb_p -Rb₂/Rb₃/Rc, -Rd enumeration in PhM-40

Objective. Aim of this work was to create a stable liposomal dosage form of native hydrophobic antitumor compound from the group of indolocarbazoles - LHS-1208. Materials and methods. Quantitative analysis of the drug content in liposomes was determined by spectrophotometry with a standard sample at X = 320 ± 2 nm. The encapsulation was investigated as the ratio of LHS-1208 concentration in the liposomal dispersion after extrusion through nylon membrane filters 0.22 ^m “Pall” to concentration LHS-1208 in liposomal dispersions before filtration. pH of the liposome was determitaned by the method of potentiometry. The size of liposomes was evaluated by nanosizer. Cytotoxic activity was studied by MTT-test. Results. Experimental liposomal models of LHS-1208 with different molar ratios of the components were obtained and analyzed. Composition with the molar ratios LHS-1208: lecithin 1:150, and lecithin : cholesterol: PEG-2000 - 1:0,2:0,003 was selected. Encapsulation percentage of LHS-1208 was 94 % and size of the vesicles was 185±10 nm. Cytotoxic activity of liposomal LHS-1208 was studied, IC₀ was 1.24 ^g/ml. Conclusion. As a result of complex pharmaceutical research determined the optimum composition of the components and the technology for production of liposomal dosage form LHS-1208.