Репозиторий Университета

© 2020 Wiley Periodicals LLC. Presently, most of anticancer drugs are high toxic for normal cells and, and as a result, they have severe side effects. Moreover, most of the formulations are lipophilic and have poor selectivity. To overcome these limitations, various drug delivery systems could be proposed. The aim of the current study was to fabricate novel polysaccharide nanocontainers (NC) by one-step ultrasonication technique and to evaluate their accumulation efficacy and cytotoxicity in 2D (monolayer culture) and 3D (tumor spheroids) in vitro models. NC with mean sizes in a range of 340–420 nm with the core-shell structure are synthetized and characterized. The NC shell is composed from diethylaminoethyl dextran/xanthan gum polyelectrolyte complex, while the hydrophobic core was loaded with the lipophilic anticancer drug thymoquinone. To enhance NC accumulation in human breast adenocarcinoma MCF-7 cells, the NC surface was modified with poly-L-lysine (PLL) or polyethylene glycol. Cell uptake of the NC loaded with Nile Red into the tumor cells was investigated by laser scanning confocal microscopy, fluorescent flow cytometry and fluorimetry. Modification of the NC with PLL allowed to obtain the optimal drug delivery system with maximal cytotoxicity, which was tested by MTT-test. The developed NC are promising for lipophilic anticancer drug delivery.

© 2020 Wiley Periodicals LLC. Presently, most of anticancer drugs are high toxic for normal cells and, and as a result, they have severe side effects. Moreover, most of the formulations are lipophilic and have poor selectivity. To overcome these limitations, various drug delivery systems could be proposed. The aim of the current study was to fabricate novel polysaccharide nanocontainers (NC) by one-step ultrasonication technique and to evaluate their accumulation efficacy and cytotoxicity in 2D (monolayer culture) and 3D (tumor spheroids) in vitro models. NC with mean sizes in a range of 340–420 nm with the core-shell structure are synthetized and characterized. The NC shell is composed from diethylaminoethyl dextran/xanthan gum polyelectrolyte complex, while the hydrophobic core was loaded with the lipophilic anticancer drug thymoquinone. To enhance NC accumulation in human breast adenocarcinoma MCF-7 cells, the NC surface was modified with poly-L-lysine (PLL) or polyethylene glycol. Cell uptake of the NC loaded with Nile Red into the tumor cells was investigated by laser scanning confocal microscopy, fluorescent flow cytometry and fluorimetry. Modification of the NC with PLL allowed to obtain the optimal drug delivery system with maximal cytotoxicity, which was tested by MTT-test. The developed NC are promising for lipophilic anticancer drug delivery.

© 2020 Elsevier Ltd Coconut water (Cocos Nucifera) is shown to be a source of essential elements present in the form of low-molecular weight stable complexes known for their bio-availability. The total element concentrations were in the range of 0.2–2.7, 0.3–1, 3–14 and 0.5–2 ppm for Fe, Cu, Mn, and Zn, respectively, and varied as a function of the origin of the nut and its maturity. Speciation was investigated by size-exclusion chromatography - inductively coupled plasma mass spectrometry (ICP MS), and hydrophilic interaction liquid chromatography (HILIC) - electrospray-Orbitrap MS. The metal species identified included: iron complexes with citrate and malate: FeIII(Cit)3(Mal), FeIII(Cit)2(Mal)2, FeIII(Mal)2, glutamine: FeIII(Glu)2 and nicotianamine: FeII(NA); copper complexes with phenylanine: CuII(Phe)2 and CuII(Phe)3 and nicotianamine: CuII(NA); zinc complexes with citrate: ZnII(Cit)2 and nicotianamine ZnII(NA) and manganese complex with asparagine MnII(Asp)2. The contributions of the individual species to the total elements concentrations could be estimated by HILIC – ICP MS.

© 2019 Most researchers associate the increase in the permeability of lipid bilayers of artificial and biological membranes observed in various experiments with the formation of hypothetical hydrophobic and hydrophilic pores. Although the existence of hydrophobic defects, as the first stage of the formation of a hydrophilic pore, was hypothesized decades ago from electroporation experiments, the difficulty of describing this stage is determined by the lack of experimental data confirming the existence or at least associated with hydrophobic pores. We explored the increase in the current variance through the lipid membrane, observed when approaching the phase transition from the side of high temperatures, and have associated it with capacitive currents arising in response to the formation of hydrophobic pores. Assuming that the number of hydrophobic pores in a membrane follows a Poisson distribution, and thus, the mean number of hydrophobic pores is equal to the variance of that number, we used the measurements of the membrane current variance to evaluate the number of hydrophobic pores. Analysis of experimental data within this model allows us to estimate the number of hydrophobic pores at or above the phase transition and shows that the number of hydrophobic pores in a membrane close to the phase transition increased 20 times compared to the number of hydrophobic pores existing in the membrane far from the melting transition.

© 2019 Most researchers associate the increase in the permeability of lipid bilayers of artificial and biological membranes observed in various experiments with the formation of hypothetical hydrophobic and hydrophilic pores. Although the existence of hydrophobic defects, as the first stage of the formation of a hydrophilic pore, was hypothesized decades ago from electroporation experiments, the difficulty of describing this stage is determined by the lack of experimental data confirming the existence or at least associated with hydrophobic pores. We explored the increase in the current variance through the lipid membrane, observed when approaching the phase transition from the side of high temperatures, and have associated it with capacitive currents arising in response to the formation of hydrophobic pores. Assuming that the number of hydrophobic pores in a membrane follows a Poisson distribution, and thus, the mean number of hydrophobic pores is equal to the variance of that number, we used the measurements of the membrane current variance to evaluate the number of hydrophobic pores. Analysis of experimental data within this model allows us to estimate the number of hydrophobic pores at or above the phase transition and shows that the number of hydrophobic pores in a membrane close to the phase transition increased 20 times compared to the number of hydrophobic pores existing in the membrane far from the melting transition.

© 2019 Most researchers associate the increase in the permeability of lipid bilayers of artificial and biological membranes observed in various experiments with the formation of hypothetical hydrophobic and hydrophilic pores. Although the existence of hydrophobic defects, as the first stage of the formation of a hydrophilic pore, was hypothesized decades ago from electroporation experiments, the difficulty of describing this stage is determined by the lack of experimental data confirming the existence or at least associated with hydrophobic pores. We explored the increase in the current variance through the lipid membrane, observed when approaching the phase transition from the side of high temperatures, and have associated it with capacitive currents arising in response to the formation of hydrophobic pores. Assuming that the number of hydrophobic pores in a membrane follows a Poisson distribution, and thus, the mean number of hydrophobic pores is equal to the variance of that number, we used the measurements of the membrane current variance to evaluate the number of hydrophobic pores. Analysis of experimental data within this model allows us to estimate the number of hydrophobic pores at or above the phase transition and shows that the number of hydrophobic pores in a membrane close to the phase transition increased 20 times compared to the number of hydrophobic pores existing in the membrane far from the melting transition.

© 2019 Most researchers associate the increase in the permeability of lipid bilayers of artificial and biological membranes observed in various experiments with the formation of hypothetical hydrophobic and hydrophilic pores. Although the existence of hydrophobic defects, as the first stage of the formation of a hydrophilic pore, was hypothesized decades ago from electroporation experiments, the difficulty of describing this stage is determined by the lack of experimental data confirming the existence or at least associated with hydrophobic pores. We explored the increase in the current variance through the lipid membrane, observed when approaching the phase transition from the side of high temperatures, and have associated it with capacitive currents arising in response to the formation of hydrophobic pores. Assuming that the number of hydrophobic pores in a membrane follows a Poisson distribution, and thus, the mean number of hydrophobic pores is equal to the variance of that number, we used the measurements of the membrane current variance to evaluate the number of hydrophobic pores. Analysis of experimental data within this model allows us to estimate the number of hydrophobic pores at or above the phase transition and shows that the number of hydrophobic pores in a membrane close to the phase transition increased 20 times compared to the number of hydrophobic pores existing in the membrane far from the melting transition.

© 2019 Most researchers associate the increase in the permeability of lipid bilayers of artificial and biological membranes observed in various experiments with the formation of hypothetical hydrophobic and hydrophilic pores. Although the existence of hydrophobic defects, as the first stage of the formation of a hydrophilic pore, was hypothesized decades ago from electroporation experiments, the difficulty of describing this stage is determined by the lack of experimental data confirming the existence or at least associated with hydrophobic pores. We explored the increase in the current variance through the lipid membrane, observed when approaching the phase transition from the side of high temperatures, and have associated it with capacitive currents arising in response to the formation of hydrophobic pores. Assuming that the number of hydrophobic pores in a membrane follows a Poisson distribution, and thus, the mean number of hydrophobic pores is equal to the variance of that number, we used the measurements of the membrane current variance to evaluate the number of hydrophobic pores. Analysis of experimental data within this model allows us to estimate the number of hydrophobic pores at or above the phase transition and shows that the number of hydrophobic pores in a membrane close to the phase transition increased 20 times compared to the number of hydrophobic pores existing in the membrane far from the melting transition.

© 2019 Most researchers associate the increase in the permeability of lipid bilayers of artificial and biological membranes observed in various experiments with the formation of hypothetical hydrophobic and hydrophilic pores. Although the existence of hydrophobic defects, as the first stage of the formation of a hydrophilic pore, was hypothesized decades ago from electroporation experiments, the difficulty of describing this stage is determined by the lack of experimental data confirming the existence or at least associated with hydrophobic pores. We explored the increase in the current variance through the lipid membrane, observed when approaching the phase transition from the side of high temperatures, and have associated it with capacitive currents arising in response to the formation of hydrophobic pores. Assuming that the number of hydrophobic pores in a membrane follows a Poisson distribution, and thus, the mean number of hydrophobic pores is equal to the variance of that number, we used the measurements of the membrane current variance to evaluate the number of hydrophobic pores. Analysis of experimental data within this model allows us to estimate the number of hydrophobic pores at or above the phase transition and shows that the number of hydrophobic pores in a membrane close to the phase transition increased 20 times compared to the number of hydrophobic pores existing in the membrane far from the melting transition.

© 2019 Most researchers associate the increase in the permeability of lipid bilayers of artificial and biological membranes observed in various experiments with the formation of hypothetical hydrophobic and hydrophilic pores. Although the existence of hydrophobic defects, as the first stage of the formation of a hydrophilic pore, was hypothesized decades ago from electroporation experiments, the difficulty of describing this stage is determined by the lack of experimental data confirming the existence or at least associated with hydrophobic pores. We explored the increase in the current variance through the lipid membrane, observed when approaching the phase transition from the side of high temperatures, and have associated it with capacitive currents arising in response to the formation of hydrophobic pores. Assuming that the number of hydrophobic pores in a membrane follows a Poisson distribution, and thus, the mean number of hydrophobic pores is equal to the variance of that number, we used the measurements of the membrane current variance to evaluate the number of hydrophobic pores. Analysis of experimental data within this model allows us to estimate the number of hydrophobic pores at or above the phase transition and shows that the number of hydrophobic pores in a membrane close to the phase transition increased 20 times compared to the number of hydrophobic pores existing in the membrane far from the melting transition.

© 2019 Elsevier Ltd Four inhibitors of human carbonic anhydrase II (hCA II) were designed based on the previously reported subnanomolar 1,3-oxazole-based sulfonamide inhibitors of the enzyme to incorporate primary and secondary amine functionality in the carboxamide side chain. The new hydrophilic compounds were found to inhibit the target isoform in sub-nanomolar to low nanomolar range with a good degree of selectivity to several other hCA isoforms. The hydrophilic character of these compounds is advantageous for intraocular residence time but not for corneal permeability which generally requires that a drug be sufficiently lipophilic. Two of the four compounds investigated, however, were found to exert comparable efficacy as 1% eye drops in PBS to that of the clinically used 2% dorzolamide (Trusopt®) eye drops. This indicated that the absorption of the compounds may occur via alternative route across conjunctiva and sclera.

©2018 by the authors. Licensee MDPI, Basel, Switzerland. Engineering of a “smart” drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer surface biomarker are critical for a targeted treatment to work. Currently, the available delivery systems use a two-dimensional monolayer of cancer cells to test the efficacy of the drug delivery system, but designing a “smart” drug delivery system to be specific for a tumour in vivo and to penetrate the inner core remains a major design challenge. These challenges can be overcome by using a study model that integrates the three-dimensional aspect of a tumour in a culture system. Here, we tested the efficacy of a functionalized folic acid-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) to specifically target and penetrate the inner core of three-dimensional avascular human pancreatic and breast tumour spheroids in culture. The copolymer was quantitatively analyzed for its hydrophobic drug encapsulation efficiency using three different chemical drug structures with different molecular weights. Their release profiles and tumour targeting properties at various concentrations and pH environments were also characterized. Using the anticancer drug curcumin and two standard clinical chemotherapeutic hydrophobic drugs, paclitaxel and 5-fluorouracil, we tested the ability of FA-DABA-SMA nanoparticles to encapsulate the differently sized drugs and deliver them to kill monolayer pancreatic cancer cells using the WST-1 cell proliferation assay. The findings of this study revealed that the functionalized folic acid-conjugated amphiphilic alternating copolymer shows unique properties as an active “smart” tumor-targeting drug delivery system with the ability to internalize hydrophobic drugs and release the chemotherapeutics for effective killing of cancer cells. The novelty of the study is the first to demonstrate a functionalized “smart” drug delivery system encapsulated with a hydrophobic drug effectively targeting and penetrating the inner core of pancreatic and breast cancer spheroids and reducing their volumes in a dose-and time-dependent manner.

© 2018 Elsevier Masson SAS A series of analogues of potent antiviral perylene nucleoside dUY11 with methylthiomethyl (MTM), azidomethyl (AZM) and HO-C1–4-alkyl-1,2,3-triazol-1,4-diyl groups at 3′-O-position as well as the two products of copper-free alkyne-azide cycloaddition of the AZM derivative were prepared and evaluated against tick-borne encephalitis virus (TBEV). Four compounds (4, 6, 8a, 8b) showed EC50 ≤ 10 nM, thus appearing the most potent TBEV inhibitors to date. Moreover, these nucleosides have higher lipophilicity (clogP) and increased solubility in aq. DMSO vs. parent compound dUY11.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Research results supporting the manufacturing technology for floating prolonged-release oral tablets based on a hydrophilic matrix with the nonselective α-adrenoblocker proroxan are presented.Wet granulation of the effervescent ingredients with the matrix produced tablets with the required buoyancy lag-time, float time, and proroxan release kinetics.

© 2017, European Biophysical Societies' Association. The Smoluchowski equation with an energy profile of a special type and an assumed hydrophobic (“half”) pore source term is used to describe the process of hydrophilic pore formation in a lipid bilayer at the gel-liquid phase transition. The source term reflects the occurrence of molecule packing defects in a lipid bilayer at phase transition. The time sequences of the pore formation and closure events are treated as non-stationary, second-order Erlang flows whose characteristics depend on the equation solution. The computed distributions of the time intervals between hydrophilic pores, and pore lifetimes agree with the previously published experimental interpulse interval and pulse duration histograms for the current fluctuations through planar bilayer membranes of DPPC immersed in a LiCl aqueous solution containing polyethylene glycol. Thus, the statistical analysis of pore formation and closure times leads us to conclude that firstly, the increased permeability of a lipid bilayer during the gel-liquid phase transition is accounted for by the emergence of additional hydrophobic defects in the heterogeneous structure of the bilayer and secondly, that the non-exponential distributions of the lipid channel closed and open times observed in experiments are evidence that the process of hydrophilic pore formation is not a one-step process but involves at least two dependent events.

© 2018, SPb RAACI.  Modern studies have shown a high plasticity and phenotypic diversity of neutrophilic granulocytes (NG) provided by different receptors, which are diagnostic markers for the functional capacity of the cell in the course of their activities. We investigated NG from peripheral blood, obtained from healthy people of both sexes aged from 26 to 66 years. Evaluation of the neutrophil membrane receptor expression was carried out by flow cytometry. The relative amount of neutrophilic granulocytes expressing membrane CD62L, CD63, CD66d receptors and the intensity of their expression were determined according to their fluorescence intensities. The surface NG membrane receptors, i.e., CD62L, CD63, CD66d were studied upon the in vitro experimental influence of the following bacterial peptides: N-formyl-methionyl-leucyl-phenylalanine (FMLP, model 1); glucosaminylmuramyldipeptide (GMDP, model 2), and simultaneous incubation of NG blood with fMLP and GMDP (model 3). The in vitro treatment with fMLP in the in vitro model was used to transform the NG phenotype of conventionally healthy subjects, expressing CD62, CD63, CD66d molecules. The treatment caused a significantly decrease in both CD62L and the CD62L expression in relative amounts of neutrophilic granulocytes with a parallel increase of CD63 expression density. The effect of GMDP on the NG phenotype of conditionally healthy subjects did not change the amount of CD62L + NG and CD63 + NG, and did not affect CD62L and CD63 expression density on the surface of NG. However, the amount of CD66d + NG was significantly increased with the unchanged expression of CD66d molecules. GMDP introduced together with the bacterial fMLP peptide was shown to neutralize some features of the NG phenotype transformation caused by fMLP, i.e., the amount of CD62L + NG was restored by 22 % and the CD62L expression density increased significantly. At the same time, GMDP did not correct the negative effect of fMLP upon the number of CD63 + NG and CD66d + NG, and on the CD63 and CD66d expression. Simultaneous addition of fMLP and GMDP did significantly increase the amount of CD66d + NG and expression density of CD63 molecules on the CD63 + NG membrane as compared to intact NG of conditionally healthy subjects. The obtained data are important in order to justify some new immunotherapeutic strategies aimed at correction of the negatively transformed NG phenotype, which accompanies some infectious and inflammatory diseases of bacterial etiology with atypical clinical course.

The formation of hydrophilic pores in lipid bilayer during phase transition is described using Smolukhowski's equation with an additional term of the hydrophobic pore source. This term is added to account for defects in lipid packing during phase transition. We assume that the temporal sequence of the pores is a stochastic process, a non -stationary second- order Erlang flow. Flow characteristics depend on the equation solution and determine the formation times of the hydrophilic pore. The calculated distribution of the durations of intervals between hydrophilic pore formations is in a good agree ment with experimental data published before. In terms of this model we describe the influence of poly (ethylene glycol) on the pore formation frequency.

Приведены результаты исследования лекарственных средств, содержащих амариллисовые алкалоиды, методом ВЭЖХ-УФ в режиме хроматографии гидрофильных взаимодействий. Объектами исследования являлись препарат «Нивалин» (Софарма, Болгария), настойки гомеопатические матричные (НГМ) подснежника Воронова и белоснежного. Аналитическая область метода составляет 2,5 – 25 мкг/мл для галантамина и ликорина. Содержание амариллисовых алкалоидов составило: в НГМ G. woronowii галантамина — 0,0005 – 0,0010 %; ликорина — 0,0012 – 0,0025 %, в НГМ G. nivalis ликорина — 0,0004 – 0,0011 %, в препарате «Нивалин» галантамина — 0,9315 %. Полученные данные могут быть использованы в фармацевтическом анализе лекарственных средств, содержащих амариллисовые алкалоиды, а также будут включены в нормативную документацию, регламентирующую их качество.

Приведены результаты исследования лекарственных средств, содержащих амариллисовые алкалоиды, методом ВЭЖХ-УФ в режиме хроматографии гидрофильных взаимодействий. Объектами исследования являлись препарат «Нивалин» (Софарма, Болгария), настойки гомеопатические матричные (НГМ) подснежника Воронова и белоснежного. Аналитическая область метода составляет 2,5 – 25 мкг/мл для галантамина и ликорина. Содержание амариллисовых алкалоидов составило: в НГМ G. woronowii галантамина — 0,0005 – 0,0010 %; ликорина — 0,0012 – 0,0025 %, в НГМ G. nivalis ликорина — 0,0004 – 0,0011 %, в препарате «Нивалин» галантамина — 0,9315 %. Полученные данные могут быть использованы в фармацевтическом анализе лекарственных средств, содержащих амариллисовые алкалоиды, а также будут включены в нормативную документацию, регламентирующую их качество.

The formation of hydrophilic pores in lipid bilayer during phase transition is described using Smolukhowski's equation with an additional term of the hydrophobic pore source. This term is added to account for defects in lipid packing during phase transition. We assume that the temporal sequence of the pores is a stochastic process, a non -stationary second- order Erlang flow. Flow characteristics depend on the equation solution and determine the formation times of the hydrophilic pore. The calculated distribution of the durations of intervals between hydrophilic pore formations is in a good agree ment with experimental data published before. In terms of this model we describe the influence of poly (ethylene glycol) on the pore formation frequency.