SELECTION OF THE COMPOSITION OF A LIPOSOMAL DOSAGE FORM OF A RUSSIAN SOMATOSTATIN ANALOGUE WITH ANTITUMOR ACTIVITY

Objective: Was to create the composition of the liposomal pharmaceutical form for injections of somatostatin analogue cyphetrylin using soybean phosphatidylcholine (SPC). Methods: The cyphetrylin, active pharmaceutical ingredient (API), developed in the Chemical Synthesis Laboratory, the N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation; SPC and polyethylene glycol-2000-distearoylphosphatidylethanolamine (PEG-DSPE, Lipoid, Germany); cholesterol ≥99% (Sigma-Aldrich, Japan). The lipid film hydration method with subsequent liposomal dispersion filtration/extrusion through nylon membrane filters was used for the phospholipid vesicle production. Based on API and lipid components in different molar ratios, we studied over 15 model liposomal compositions and assessed each lipid's impact in use on quality attributes of resulting dispersions. Derived model samples of liposomal dispersion were estimated in terms of quality and efficiency of cyphetrylin encapsulation into vesicles, their average size and the surface charge (zeta potential), polydispersity index (PDI) and dispersion viscosity. We used spectral photometry, dispersion laser spectroscopy, electrophoretic particle mobility assay, and viscometry to assess these features. Results: Pharmaceutical form components' desirable molar ratios determined: cyphetrylin/SPC at 1:60.0 and SPC/cholesterol/PEG-DSPE at 1:0.2:0.004, were determined. This composition allows cyphetrylin liposomal dispersion production with relatively stable vesicles of uniform size, 176 nm in diameter, and a 100% maximum rate of API encapsulation into the bilayer. Conclusion: Technological and chemical/pharmaceutical studies resulted in selecting a preferable composition of an injectable liposomal pharmaceutical form model of somatostatin analog-based on the SPC

DEVELOPMENT OF A TECHNOLOGY FOR PRODUCING A STABLE INJECTABLE DOSAGE FORM OF A HYDROPHOBIC INDOLOCARBAZOLE DERIVATIVE

Objective: Development of a technology for the production of a stable injectable dosage form (IDF) of indolocarbazole derivative LHS-1269. Methods: LHS-1269 is an active pharmaceutical ingredient that was synthesized in the N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation. The IDF includes dimethyl sulfoxide (DMSO), 95% ethanol, Kollidon® 17PF and water for injection. Magnetic stirrer and overhead stirrer with a propeller stirring element were used to prepare the model solution of the IDF of LHS-1269. Sterilizing filtration of the solution was performed with 0.2−0.22 um polycarbonate, cellulose, polyvinylidene fluoride, polyethersulfone and nylon membrane filters. The aqueous solution of LHS-1269 was lyophilized in Edwards Minifast DO.2 freeze dryer. Assay of LHS-1269 was performed by spectrophotometry at 320±3 nm. Potentiometry was used to measure pH, a viscosimetry method was used to measure the viscosity of the solutions. The average weight was estimated by weighing a sample of 10 vials with the concentrate. Results: 0.5% aqueous solution of LHS-1269 was produced by mixing the solution of the active substance in DMSO and ethanol with an aqueous solution of polyvinylpyrrolidone gradually at the ratio of LHS-1269/DMSO/ethanol/Kollidon® of 1/11/32/40 by weight. The aqueous solution of the study substance cannot be lyophilized, so a sequence of technological operations was presented to produce an anhydrous concentrate “LHS-1269, concentrate for solution for injection and infusion 25 mg”. Conclusion: A technology was developed to produce a stable IDF of a hydrophobic indolocarbazole derivative LHS-1269, a high-potential antitumor drug

Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration

Human genetic factors predispose to tuberculosis (TB). We studied 7.6 million genetic variants in 5,530 people with pulmonary TB and in 5,607 healthy controls. In the combined analysis of these subjects and the follow-up cohort (15,087 TB patients and controls altogether), we found an association between TB and variants located in introns of the ASAP1 gene on chromosome 8q24 (P = 2.6 × 10−11 for rs4733781; P = 1.0 × 10−10 for rs10956514). Dendritic cells (DCs) showed high ASAP1 expression that was reduced after Mycobacterium tuberculosis infection, and rs10956514 was associated with the level of reduction of ASAP1 expression. The ASAP1 protein is involved in actin and membrane remodeling and has been associated with podosomes. The ASAP1-depleted DCs showed impaired matrix degradation and migration. Therefore, genetically determined excessive reduction of ASAP1 expression in M. tuberculosis–infected DCs may lead to their impaired migration, suggesting a potential mechanism of predisposition to TB

Survival of Civilian and Prisoner Drug-Sensitive, Multi- and Extensive Drug- Resistant Tuberculosis Cohorts Prospectively Followed in Russia

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Risk factors for drug-resistant tuberculosis patients in Lithuania, 2002–2008: Table 1–

n/

Quality control of fat fraction quantification in magnetic resonance imaging: A two-center phantom study

BACKGROUND: Assessment of quantitative parameters using magnetic resonance imaging (MRI) is a relevant trend. Fat fraction (FF) calculation provides new opportunities for accurate diagnosis and will replace invasive methods such as biopsy in the future. Quantification will enable reliable dynamic monitoring and assessment of drug therapy. However, radiologists and clinical specialists must be confident in the accuracy and reliability of the quantitative measures. AIM: To assess the accuracy of quantitative FF measurement using phantom simulation in the range of 0% to 60%. METHODS: Emulsions of the oil-in-water type were chosen to simulate the objects of the study. Concentrations of vegetable oil-based emulsions were presented in the range of 0% to 60%. Tubes containing the emulsions were placed in a cylindrical phantom. Scans were performed on an Optima, MR450w 1.5 Tesla (GE) tomograph in Lava Flex mode and on an Ingenia, 1.5 Tesla (Philips) tomograph in DIXON mode. FF was determined by formulas using images in In-phase and Out-phase based on signal characteristics (FF=[InOut]/2∙In∙100) and images weighted by Water and Fat data (FF=Fat/[Fat+water]∙100. RESULTS: The accuracy of the fat percentage measurement with the DIXON technique was identical to that of the Lava Flex. The data of the measured fat concentration were systematically overestimated in relation to the target values by an average of 57.6% with an average absolute difference of 17.2%. In addition, an irregular underestimation in the range of 20% to 40% was detected. CONCLUSIONS: Phantom simulation using direct oil-in-water emulsions allowed to control the performance of the Dixon sequences in quantifying the FF. For correct FF quantification, calculation from Water and Fat image data using the formula FF=Fat/(Fat+water)∙100 is preferable. Calculations based on In-phase and Out-phase images provide ambiguous results. The FF calculation in the Lava Flex and DIXON modes must be performed with a correction factor. The use of the phantom allows proper quality control and calibration of the MRI scanner and makes quantitative fat measurement widely available

Global neopolitics: risks of sustainable development of modern society

The article analyzed the peculiarities of the development of modern society. It has been found that the social development of Ukraine corresponds to global trends and is aimed at participating in global cooperation. The matrix of world development, as well as for Ukraine is characterized by turbulence of the processes of functioning of society, which is manifested in the activation of a significant number of negative trends: the economic inability of a number of countries, the moral degradation of humanity, the intensification of protest sentiments by the intensification of terrorist activities. Therefore, these aspects allow to characterize modern global society as a “society of risk”. It was found that in order to achieve its sustainable development, it is necessary: to form a system of positive social, economic, environmental, political and cultural values, not only among the political elite, but also in other socially conscious strata; to restore legitimacy and trust in the existing institutions of power; to develop institutional mechanisms for predicting and managing risks, etc

Some global economic realities and environmental impact in the context of the pandemic: causes and trends

The article examines some of the world’s economic realities in the context of a pandemic. It is noted that the world will experience the economic consequences of the pandemic for several more years. Well-established supply chains have been disrupted, some cranes have fallen into deep recessions, and the recovery of some of the world’s leading economic sectors is still in doubt. No one could have imagined that such a large industry as the oil industry, in the literal sense, will go into negative territory, and the air carriers will remain practically out of work. However, this took place in real life and was reflected in economic history. Therefore, in order to overcome these negative trends in the future, it is necessary to learn from the mistakes of today, this will make it possible to prevent the shutdown of economically important industries in the future and allow the economy to develop, even if not at a high pace, but still within the framework of a certain progressive development.The purpose of the work is to analyze some of the economic events that took place during the pandemic in order to identify the causes of their occurrence and further development trends