Scientific relevance. In recent years, antimicrobial resistance in pathogenic microorganisms has become a global problem that threatens the health of humans and animals and poses a risk to the biosafety of Russia.Aim. The study aimed to analyse the prevalence of antimicrobial resistance, consider the risks and medical consequences of this biological phenomenon, and suggest ways to optimise the use of existing antimicrobial agents and search for new ones.Discussion. The emergence of antibiotic resistance in bacteria is a natural biological process; the selection of resistant microorganisms occurs constantly with the use of the entire spectrum of antimicrobial agents in healthcare, agriculture, and other fields. The World Health Organisation (WHO) monitors these processes using the Global Antimicrobial Resistance Surveillance System (GLASS). Russia has adopted the Strategy to prevent the spread of antimicrobial resistance in the Russian Federation to 2030. The country has established a regulatory framework that supports the operation of the national antimicrobial resistance prevention system. The strategy to prevent the spread of antimicrobial resistance is being implemented through making organisational arrangements and developing novel medicines with mechanisms of action based on an understanding of the molecular mechanisms of infection and resistance. This review considers the main approaches to designing exploratory studies and evaluating the antimicrobial activity of the innovative molecules obtained. The rapid development of synthetic biology increases the likelihood of creating synthetic biological pathogens with high virulence and resistance to antimicrobial agents, which might pose risks of artificial epidemics.Conclusions. The antimicrobial resistance prevention system in Russia should be considered a strategically essential medical technology ensuring the biosafety of the country and the people.

Examples of modern research conducted within the framework of the concept of human improvement with the use of artificial intelligence technologies, genomics, nanotechnology and robotics to improve the functional characteristics of the human body are considered. It is shown that the creation of bioengineering systems «man-machine» can be considered as a supertechnology of the XXI century, which is capable of influencing the entire course of human history, the biosphere, and the process of its development and application may turn out to be a new area of confrontation, the beginning of a «supernova» arms race. In connection with the above, prospective and applied research in this area should be considered in the context of the national security strategy. Along with the work on modeling, creation and application of individual bioengineering systems «man-machine», it is necessary to intensify the development of legal, bioethical and other norms and rules that ensure both technological development (In a given corridor of possibilities) and a high level of safety (by type) of new technologies and developments.

The plant alkaloid sanguinarine has antitumour, antiangiogenic, antimicrobial and antiviral activity. However, the maximum manifestation of the therapeutic potential of sanguinarine is hindered by relatively low bioavailability and a number of side effects. To increase the bioavailability and effectiveness of the therapeutic effect, sanguinarine was introduced into the pH-sensitive liposomes by the remote loading method. The average diameter of liposome particles with sanguinarine was 107.4 +/- 3.7 nm; the zeta potential -12.7 +/- 1.5 mV. The effectiveness of the inclusion of sanguinarine in liposomes was 75.94 +/- 2.18%. In the model experiments, the dynamics of the release of sanguinarine from liposomes was studied, and the prolonged release pattern was demonstrated. The cytotoxic activity (CTA) of liposomal sanguinarine against tumour cells of the MCF-7, HeLa and K 562 lines was studied in vitro. Liposomal sanguinarine exhibited a dose-dependent CTA for tumour cells of all the lines studied; the highest CTA was seen with HeLa cells (IC50 3.2 mu M). For this cell line CTA of liposomal sanguinarine significantly (similar to 2.2 times) exceeded the activity of the free drug. A comparative study of liposomal and free sanguinarine with respect to the ability to induce apoptosis of HeLa cells has also been performed. At a concentration of 5 mu M the liposomal sanguinarine induced apoptosis in 41.96% of tumour cells, whereas the free sanguinarine - only in 20.32% of the cells. It is likely that the use of sanguinarine in the composition of pH-sensitive liposomes can promote its effective release from the acid medium of the endosomal compartment of tumour cells and the manifestation of a toxic effect. The presented data allow to consider liposomal sanguinarine as a promising antitumour agent.

Silymarin (SM) from Silybum marianum (L.) is a sum of flavolignans (silibinin, silychristin, silydianin, and isosilibinin), exhibiting a wide spectrum of biological activity and having anti-inflammatory, antitumor, hepatoprotective, immunomodulatory effects. Using a modified emulsion method with solvent evaporation, lipid nanoparticles with silymarin (LNP-SM) were obtained, the size of which was 257 ± 6 nm, and the ζ potential was –20.8 ± 1.6 mV. The efficiency of SM inclusion in the LNP-SM was 89.8%, the loading degree was 5.4%. The release of CM from the composition of the resulting nanoparticles was prolonged; after 48 h, only 68.3 ± 5.4% of the active substance was released into the dialysis medium. The dynamics of the inclusion/release of SM in the composition of LNP into the films of bacterial cellulose (BC) produced by the Gluconacetobacter hansenii GH-1/2008 strain has been studied. It was shown, that after 24 h of incubation the maximum of BC film saturation with SM reached 0.745 ± 0.038 mg/cm2, and the maximum release was 0.520 ± 0.041 mg/cm2. It was demonstrated that both LNP-SM sols and samples of BC saturated with LNP-SM exhibited low hemolytic activity, which indicates the potential biosafety of these preparations. The preparation LNP-SM, in contrast to free SM, exhibited fungistatic action against the fungi of A. niger and C. albicans. Both free SM and LNP-SM suppressed the growth of gram-positive bacteria; however, the effect of LNP-SM was much more effective. The minimum inhibitory concentration of the LNP-SM preparation for B. subtilis and B. coagulans was 105 and 210 μg/mL, respectively. The possibility of developing biocompatible coating materials based on BC saturated with LNP-SM is discussed.

The article is devoted to biological threats and ensuring biosafety in Russia. Special attention is given to the relevance of this work. The article contains such sections as introduction, biological threats, ensuring biological safety and conclusion. In accordance with Presidential Decree No. 97, the characteristics of the most significant infectious agents that can potentially be used as a biological weapon are given. At the same time, the issue of the rapid spread of antibiotic resistance and the introduction of genetically modified objects into widespread practice is being considered. The necessity of improving the regulatory framework and the biosafety system as a whole is substantiated.

The article is devoted to biological threats and ensuring biosafety in Russia. Special attention is given to the relevance of this work. The article contains such sections as introduction, biological threats, ensuring biological safety and conclusion. In accordance with Presidential Decree No. 97, the characteristics of the most significant infectious agents that can potentially be used as a biological weapon are given. At the same time, the issue of the rapid spread of antibiotic resistance and the introduction of genetically modified objects into widespread practice is being considered. The necessity of improving the regulatory framework and the biosafety system as a whole is substantiated.

Benzophenanthridine alkaloid sanguinarine from Macleaya macrocarpa shows antitumor and anti-angiogenic activity, among others. Some side effects of sanguinarine, which significantly limit the possibilities of its therapeutic use, are described. To increase the effectiveness of its therapeutic effect, sanguinarine was introduced into the pH-sensitive liposomes by remote loading using ammonium dihydrogen phosphate. pH-sensitive liposomes, appearing in the acidic environment of the tumor or endosomal compartment, release sanguinarine, which causes the death of tumor cells. The average diameter of the liposome particles measured by the method of dynamic light scattering was 112.6 ± 1.8 nm; the zeta potential was –13.9 ± 1.7 mV. The effectiveness of the inclusion of sanguinarine in liposomes was 89.54 ± 2.13%. The dynamics of release of sanguinarine from the composition of a liposome preparation was studied, and the prolonged release pattern was demonstrated. The cytotoxic activity (CTA) of liposomal sanguinarine against prostate cancer cell lines LNCaP, DU 145, and PC-3 was studied. Liposomal sanguinarine exhibited dose-dependent CTA against cells of all the studied lines in the micromolar range of concentrations. The highest CTA of liposomal sanguinarine was seen against the hormone-sensitive LNCaP cells (IC50 2.86 μM). For the hormone-independent cells of the DU 145 and PC-3 lines, the cytotoxic activity of liposomal sanguinarine was somewhat lower and amounted to 3.37 μM and 3.63 μM, respectively. A dose-dependent induction of apoptosis of LNCaP, DU 145, and PC-3 cells was also demonstrated. The liposomal sanguinarine with high efficiency induced apoptosis of both hormone-sensitive and hormone-independent cells. The liposomal sanguinarine at a concentration of 8 μM induced apoptosis in 93.14% of LNCaP cells, 90.65% of DU 145 cells, and 98.12% of PC-3 cells. Thus, liposomal sanguinarine can be considered as a promising antitumor agent for the therapy of both hormone-sensitive and hormone-independent tumors.