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 aim of the study was to obtain and characterize liposomal silibinin, as well as to study its antitumor and antimicrobial activity. Liposomes were obtained by hydration of a thin-layer film with a buffer solution followed by multiple freezing-thawing of the dispersion of phosphatidylcholine-cholesterol-silibinin. It has been established that liposomal silibinin has an inhibitory effect against liver (HepG2 line) and prostate gland (DU145 line) tumor cells. In addition, liposomalosilinin has a pronounced antibacterial effect against bacteria and a fungistatic effect on toxigenic micromycetes, which may indicate its effectiveness as an antimicrobial and fungistatic agent for reducing the negative effect of mycotoxins of mold fungi.

A stable preparation of agaricinic acid nanoparticles was obtained. The mean hydrodynamic size of nanoparticles according to photon correlation spectroscopy was 200 nm and zeta potential was -57 mV. Cytotoxic activity of agaricinic acid nanoparticles against human HepG2 hepatoma cells was evaluated. Nanoparticles with a low concentration of agaricinic acid stimulated and with high concentration - suppressed metabolic activity and viability of hepatoma cells. The EC50 for the stimulating effect was 32.8 μg/ml, and the IC50=602.1 mg/ml. The preparation of agaricinic acid nanoparticles can be used in medicine as a potential antitumor agent.

Chitosan beads with colloidal silver nanoparticles inclued in the polymer matrix have been obtained by the introduction of chitosan into an acidified nanosilver sol. Dual interconnection of drops of the resulting solution was then carried out by ionotropic gelation at the first stage and covalent crosslinking of the polymer matrix with adipic acid at the second stage. The surface morphology of the obtained beads was studied by scanning electron microscopy. Data of Fourier transform IR spectroscopy confirmed the formation of covalent bonds between chitosan and adipic acid. The antibacterial activity of obtained beads against S. aureus and E. coli was evaluated using agar diffusion test. It was shown that the сhitosan beads modified with nanostructured silver exhibited an antibacterial effect against the tested strains, and they can be used as a basis for creating biodegradable wound healing dressings with a prolonged antibacterial effect. chitosan, silver nanoparticles, antibacterial activity, wound dressings This work was supported by the "Russian Academic Excellence Project 5-100". The study was carried out with the financial support of the Russian Foundation for Basic Research in the framework of the Scientific Project no. 18-29-18039.

Sanguinarin is a plant alkaloid with a wide spectrum of biological activity. The effectiveness of sanguinarin can be increased by its integration into liposomal nanoparticles. The aim of this study was to obtain and purify the pegylated liposome sanguinarine, to study its properties, as well as antitumor and antimicrobial activity in vitro. Pegylated liposome nanoparticles containing sanguinarinewere obtained. The size of the liposomes was 61.8+5.7 nm; the effectiveness of the inclusion of sanguinarine in liposomes was 82.3+4.9%. The article studies the release of sanguinarin from liposome particles and demonstrates its prolonged nature. An in vitro study showed that liposomal sanguinarine exhibited dose-dependent cytotoxic activity against tumor cells of MCF-7 (12.8 μM), L1210 (17.4 μM), A431 (18.67 μM) and HepG2 (20.7 μM). The antimicrobial effect of the liposome form of the drug was established for Gram-positive (B.subtilis ATC 6633 and B.coagulans 429) and Gram-negative (E.coli ATCC 8739) bacteria, as well as opportunistic fungi Aspergillus ustus 6K. The results indicate the prospects of further study of pegylated liposomal sanguinarine as an antitumor and antimicrobial agent.

Silver nanoparticles were synthesized by chemical reduction of silver nitrate using arabinogalactan polysaccharide as a reducing agent and a stabilizer. The average size of nanoparticles, obtained by analyzing TEM-images, was 10.8[Formula: see text]nm; zeta potential [Formula: see text][Formula: see text]mV. A study of the sol by electron diffraction showed that silver in the sample is in metallic form. The resulting preparation of silver nanoparticles showed both antibacterial and antifungal activity. A pronounced antibacterial activity of silver nanoparticles was demonstrated both in relation to conditionally pathogenic gram-positive (Bacillus subtilis and B. coagulans) and gram-negative (Escherichia coli) bacteria. Silver nanoparticles also possess antifungal activity against macromycete Fomitopsis sp., as well as two strains of micromycetes Trichoderma citrinoviride and Fusarium sporotrichioides. Using the methods of light and fluorescence microscopy, MTT-analysis and Real-time cell analysis, the cytotoxic activity of silver nanoparticles was investigated on HepG2 human hepatocellular carcinoma cells. It was demonstrated that nanoparticles cause a suppression of cell metabolic and proliferative activity, as well as dose-dependent induction of cell death (average relative EC[Formula: see text] value was [Formula: see text]g/ml). The preparation of silver nanoparticles stabilized by arabinogalactan can be used in medicine, as a potential antimicrobial and antitumor agent.

The article discusses the development of a new method of producing Laetiporus sulphureus (Bull.) Murrill basidiomycete mycelium immobilized on a bacterial cellulose matrix. Mycelium contains biologically active compounds with antimicrobial activity against Gram-positive bacteria, including resistant staphylococcus. The aim of the work was to obtain immobilized mycelium by co-cultivation of L.sulphureus with the producer of bacterial cellulose Gluconacetobacter hansenii. The authors found that when co-culturing the basidial L.sulphureus strain with the bacterial cellulose producing G.hansenii strain, productivity increases by 3.2 times on H5/1 synthetic medium and by 1.9 times on natural Maltax-10 medium (concentration 5%). The resulting immobilized L.sulphureus mycelium has antibacterial properties; its aqueous extracts contain glucans.

The article describes the development of a new method for obtaining mycelium of the basidiomycete Fomitopsis officinalis (Vill.:Fr.) Bond. Et Sing., immobilized on a matrix of bacterial cellulose. Mycelium of F.officinalis contains biologically active compounds, the most important of which is agaricic acid. The known methods for producing mycelium using surface solid-phase and submerged cultivation make it possible to obtain biomass of mycelium in an amount of 3.5 to 5 g/L of absolutely dry mass. Considering that F.officinalis is a xylotrophic macromycete, the use of cellulose as a food source can show higher productivity in the cultivation of mycelium in artificial biotechnological systems. The aim of the work was to obtain immobilized mycelium by co-cultivation of F.officinalis with the producer of bacterial cellulose Gluconacetobacter hansenii. The research established that with the co-cultivation of the basidial strain of F.officinalis with G.hansenii, the producer strain of bacterial cellulose, the productivity increases by 3.2 times on synthetic medium H5/1 and on the natural medium Maltax-10 (5% concentration) — by 1.9 times. The obtained immobilized mycelium of F.officinalis contains agaricic acid, the amount of which is 5.4—6.8%. The study of the structure of agaricic acid, isolated from the mycelium of the strain, was carried out by comparing the 13C NMR spectra with the spectra of a standard sample (Sigma cat). The results of the research confirmed the identity of the compounds.

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.

Sanguinarine is a benzophenanthridine alkaloid contained in Chelidonium majus, Macleaya microcarpa, Sanguinaria canadensis etc. Sanguinarine has a broad spectrum of biological activity, including antimicrobial and antifungal, antiinflammatory, antiadrenergic and antitumour effect. Using a modified emulsion method with solvent evaporation, lipid nanoparticles including sanguinarine were obtained, with a size of 182.3±6.7 nm and a zeta potential of -20.6 ± 1.3 mV. The efficiency of the inclusion of sanguinarine in nanoparticles was 72.9 ± 1.5%. The release of the active substance from nanoparticles had prolonged nature (only 18.2% of sanguinarine was released after 4 h of the experiment, and 39.4% after 24 h). Lipid nanoparticles with sanguinarine were able to effectively sorb and gradually release from the matrix of bacterial cellulose produced by the strain Komagataeibacter nataicola BC-B0007. The maximum inclusion of sanguinarine in the composition of nanoparticles in hydrated films of bacterial cellulose was achieved in 3 h and was 848.0 ± 43.2 μg/g. The obtained bacterial cellulose films carrying lipid nanoparticles with sanguinarine were investigated for their ability to exert an antimicrobial effect in vitro. The sanguinarine released from the films effectively suppressed the growth of Gram-negative and Gram-positive bacteria, and also showed fungistatic activity against conditionally pathogenic fungi.

Синтезированы наночастицы серебра с использованием для их восстановления и стабилизации арабиногалактана и диоктилсульфосукцината натрия. Средний гидродинамический размер наночастиц, определенный по данным фотонной корреляционной спектроскопии, составлял 30 нм, дзета-потенциал –34.04 ± 1.54 мВ. По данным метода электронной дифракции серебро в образце золя находится в металлической форме. Препарат наночастиц серебра проявлял антибактериальную активность в отношении условно-патогенных грамотрицательных (Escherichia coli) и грамположительных (Bacillus subtilis и B. coagulans) бактерий. Наночастицы серебра также обладали антифунгальной активностью в отношении штаммов фитопатогенных грибов рода Fusarium sporotrichioides и F. solani. Проведено исследование цитотоксической активности наночастиц серебра в отношении клеток гепатомы печени человека линии HepG2. Продемонстрировано ингибирующее действие наночастиц серебра в отношении метаболической активности и жизнеспособности опухолевых клеток. Средние относительные значения EC50 для наночастиц серебра составляли 1.5 ± 0.4 и 41.2 ± 3.9 мкг/мл. Препарат стабилизированных наночастиц серебра может найти применение в медицине в качестве потенциального антимикробного и противоопухолевого средства, а также в сельском хозяйстве в качестве средства подавления роста фитопатогенных грибов.

Bacterial cellulose is a biomaterial produced by Gluconacetobacter hansenii bacteria with peculiar properties. The aim of this research was to assess three methods for washing bacterial cellulose from producer cells: 5% SDS, RIPA and RIPA with the addition of nucleases. Atomic force microscopy showed that all methods provide the removal of bacterial cells. The authors carried out a quantitative estimation of residual DNA on the bacterial cellulose matrix and demonstrated a significant difference (p < 0.05) in the DNA content between the group of RIPA with the addition of nucleases and the non-washed matrix. The authors evaluated the cytotoxicity of the extracts and the matrix of bacterial cellulose in regard to protozoa (Tetrahymena) and the mammalian cell culture (NIH/3T3), respectively. The results from the assay with the Biolat device and the MTT assay indicated that the samples are not cytotoxic. The Live/Dead assay of NIH/3T3 showed that bacterial cellulose is an adhesive matrix in regard to mammalian cells and maintains cell viability. In accordance with the authors' data, a bacterial cellulose matrix may provide with washing 5% SDS and RIPA; however, the addition of nucleases is necessary to reduce residual bacterial DNA.

Sanguinarine is a benzophenanthridine alkaloid of plant origin showing antitumour, anti-inflammatory and a number of other activities. To increase the effectiveness of its therapeutic effect, sanguinarine was introduced into the pH-sensitive liposomes by the remote loading method using ammonium citrate. The average diameter of the obtained liposomes was equal to 144.8 +/- 2.3 nm; zeta potential was equal to -16.3 +/- 1.5 mV, the effectiveness of sanguinarine inclusion in liposomes was 68.7%. The release of sanguinarine from liposomes was prolonged; the lowest level of release was observed in a medium with a pH of 7.4, the highest at pH 5.5, which may be useful in preventing the release of the active substance in the blood stream and, conversely, in activating its release in the tumour growth zone. The cytotoxic activity of liposomal sanguinarine against cells of human squamous carcinoma A431 (IC50 9.5 mu M) was significantly higher than its activity against the normal epidermal keratinocytes (NHEK) (IC50 25.1 mu M). The drug also caused an effective dose-dependent induction of apoptosis in tumour cells of A431, while not affecting normal cells. Thus, liposomal sanguinarine can be considered as a promising antitumour agent acting on tumour cells by inducing apoptosis and exhibiting low cytotoxicity to normal human cells.

— Silver nanoparticles were synthesized using arabinogalactan and sodium dioctyl sulfosuccinate to reduce and stabilize them. The average hydrodynamic size of the nanoparticles, determined by photon correlation spectroscopy, was 30 nm, and the zeta potential was –34.04 ± 1.54 mV. According to the electron diffraction method, silver in the sol sample is in metallic form. The preparation of silver nanoparticles showed antibacterial activity against opportunistic Gram-negative ( Escherichia coli ) and Gram-positive ( Bacillus subtilis and B. coagulans ) bacteria. Silver nanoparticles also had antifungal activity against strains of phytopathogenic fungi of the genus Fusarium sporotrichioides and F. solani . A study of the cytotoxic activity of silver nanoparticles was made on human hepatoma cells of the HepG2 line. The inhibitory effect of silver nanoparticles on the metabolic activity and viability of tumor cells has been demonstrated. The average relative EC 50 values for silver nanoparticles were 1.5 ± 0.4 μg/ml and 41.2 ± 3.9 μg/mL. The preparation of stabilized silver nanoparticles can find application in medicine, as a potential antimicrobial and antitumor agent, as well as in agriculture as a means of suppressing growth of phytopathogenic fungi.

AIM: to obtain and investigate the activity of silver nanoparticles stabilized with arabinogalactan in relation to clinically relevant strains of filmforming microorganisms. MATERIALS AND METHODS: silver nanoparticles were obtained by reduction from silver nitrate in the presence of arabinogalactan with additional stabilization with dioctyl sodium sulfosuccinate. The shape and size of the nanoparticles were determined by the method of transmission electron microscopy, the zeta potential by the method of electrophoretic light scattering. The study of the effect of the nanoparticles on biofilm formation was carried out on 17 clinically relevant strains of bacteria isolated from blood culture and the clinical biomaterial of postoperative patients. RESULTS: the silver nanoparticles with an average diameter of 11.4 nm and a zeta potential of –24 mV were obtained. The minimum inhibitory concentration of the nanoparticles in relation to planktonic form of bacteria was 120 µg/ml; the use of the drug at a concentration of 100 µg/ml reduced the amount of CFU by 7 orders of magnitude compared with the initial culture. The study of the effect of silver nanoparticles on the formation of biofilms showed that, in the presence of the drug, the growth of biofilms was significantly reduced; at a drug concentration of 150 µg/ml, the growth of bacterial films was completely suppressed. Incubation of the formed daily biofilms with the silver nanoparticles in the concentration range from 150 to 120 µg/ml for 48 h resulted in the partial or complete destruction of the biopolymer matrix. CONCLUSION: the studied preparation of silver nanoparticles has a great potential for use in the treatment of infectious diseases caused by biofilm forming microorganisms.

In the present work, a promising method was proposed for the formation of new functional nanocomposite materials based on bacterial cellulose and Au nanoparticles obtained by a biocompatible and environmentally friendly metal vapor synthesis. The structure and composition of the composite films surface were studied by XPS, SEM, and IR spectroscopy. It was determined that Au nanoparticles effectively chemisorb the bacterial cellulose nanofibrils forming nanoparticles with a size of about 25 nm with a metal core-hydrocarbon shell structure.