Ultrahigh-throughput screening (uHTS) techniques can identify unique functionality from millions of variants. To mimic the natural selection mechanisms that occur by compartmentalization in vivo, we ...developed a technique based on single-cell encapsulation in droplets of a monodisperse microfluidic double water-in-oil-in-water emulsion (MDE). Biocompatible MDE enables in-droplet cultivation of different living species. The combination of droplet-generating machinery with FACS followed by next-generation sequencing and liquid chromatography-mass spectrometry analysis of the secretomes of encapsulated organisms yielded detailed genotype/phenotype descriptions. This platform was probed with uHTS for biocatalysts anchored to yeast with enrichment close to the theoretically calculated limit and cell-to-cell interactions. MDE–FACS allowed the identification of human butyrylcholinesterase mutants that undergo self-reactivation after inhibition by the organophosphorus agent paraoxon. The versatility of the platform allowed the identification of bacteria, including slow-growing oral microbiota species that suppress the growth of a common pathogen, Staphylococcus aureus, and predicted which genera were associated with inhibitory activity.
In this work, the preparation procedure and properties of anionic magnetic microgels loaded with antitumor drug doxorubicin are described. The functional microgels were produced via the in situ ...formation of iron nanoparticles in an aqueous dispersion of polymer microgels based on poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAM-PAA). The composition and morphology of the resulting composite microgels were studied by means of X-ray diffraction, Mössbauer spectroscopy, IR spectroscopy, scanning electron microscopy, atomic-force microscopy, laser microelectrophoresis, and static and dynamic light scattering. The forming nanoparticles were found to be β-FeO(OH). In physiological pH and ionic strength, the obtained composite microgels were shown to possess high colloid stability. The average size of the composites was 200 nm, while the zeta-potential was -27.5 mV. An optical tweezers study has demonstrated the possibility of manipulation with microgel using external magnetic fields. Loading of the composite microgel with doxorubicin did not lead to any change in particle size and colloidal stability. Magnetic-driven interaction of the drug-loaded microgel with model cell membranes was demonstrated by fluorescence microscopy. The described magnetic microgels demonstrate the potential for the controlled delivery of biologically active substances.
The rapid growth in the prevalence of infectious diseases requires timely action from drug developers. In recent years, the COVID-19 pandemic has demonstrated the unpreparedness of the population for ...such emergencies. The introduction of modern methods of Design of Experiments (DoE) is required to accelerate the process of drug development and bring a drug to market. The main objective of this study was to develop an ion-triggered in situ system for intranasal delivery of VLP using a Quality by Design approach. Based on a literature review and initial studies, the key QTPP, CQA, CPP, and CMA were identified to develop a novel delivery system for virus-like particles. As a result of the studies on the quality attributes of the developed delivery system, an ion-triggered in situ gel meeting all the specified parameters was obtained using the Quality by Design method.
Water solubility of prothionamide and its solid dispersions with polyethylene glycol-1500, polyvinylpyrrolidone-10000, and β-cyclodextrin was studied. The most promising results were obtained with ...the solid dispersion with polyvinylpyrrolidone, which provided a 2.6-fold general increase of drug’s solubility and about a 6-fold dissolution rate increase, the maximal values among the studied drug forms. The results of complex physicochemical studies suggested that the improved drug release was due to micronization and solubilizing action of the polymer. A principal factor was the destruction of the crystal lattice and formation of amorphous particles in the solid dispersion. The obtained data can be useful for the development of modified pharmaceutical forms of prothionamide with improved drug release profile.
In vitro selection of antibodies from large repertoires of immunoglobulin (Ig) combining sites using combinatorial libraries is a powerful tool, with great potential for generating in vivo scavengers ...for toxins. However, addition of a maturation function is necessary to enable these selected antibodies to more closely mimic the full mammalian immune response. We approached this goal using quantum mechanics/molecular mechanics (QM/MM) calculations to achieve maturation in silico. We preselected A17, an Ig template, from a naïve library for its ability to disarm a toxic pesticide related to organophosphorus nerve agents. Virtual screening of 167,538 robotically generated mutants identified an optimum single point mutation, which experimentally boosted wild-type Ig scavenger performance by 170-fold. We validated the QM/MM predictions via kinetic analysis and crystal structures of mutant apo-A17 and covalently modified Ig, thereby identifying the displacement of one water molecule by an arginine as delivering this catalysis.
Introduction. The article is devoted to the current but understudied problem in psychology: the speed of social processes. The interdisciplinary approach (theories of P. Virilio, H. Rosa) is used ...when discussing the issue, substantiating the purpose and hypotheses of the study. The article is aimed to propose the author’s Attitudes towards the Speed of Social Processes inventory, determine its psychometric properties and test its validity. The attitude towards speed is considered as an aspect of subjective time. Methods. The sample size was 521 people. The average age was 31.5 years (min – 21, max – 45), 48.8% of them were men, and 65.6% with higher education; the sample included advanced workers and graduates of vocational educational institutions (work experience 2-3 years). To assess convergent validity, the following were used: Questionnaire of Attitudes towards Technology by G. U. Soldatova, T. A. Nestik, E. I. Rasskazova, E. A. Dorokhova; Personal Flexibility at the Labour Sphere Scale by A. N. Diomin, O. V. Kireeva; scales measuring attitudes towards remote technologies. To assess the criterion validity, the graduates of vocational educational institutions and advancing-age workers were compared (age criterion). Exploratory and confirmatory factor analysis, Spearman’s ρ correlation coefficient and the Mann-Whitney U-test were used. Results. The structure of the inventory is set apart and confirmed. It includes two scales: awareness of the social acceleration (the cognitive component) and rejection of the social acceleration (the affective component); their internal and retest reliability is acceptable. The scales correlate with technophilia, technophobia, technopessimism, attitude to remote technologies, and flexibility of the individual at the labour sphere. It has been established that graduates of vocational educational institutions demonstrate a significantly higher level of awareness and emotional acceptance of social acceleration compared to advanced-age workers. Discussion. The correlations and differences expected in theoretical terms are empirically confirmed. The conclusion is made: the Attitudes Towards the Speed of Social Processes inventory is a new compact psychodiagnostic tool that can be used in psychological and interdisciplinary research. Ideas are formulated that aim to expand the list of criteria for the validity of the new inventory.
Taking into account the current Product specification file,
the aim
of the work
was
to develop the composition and technology for obtaining effervescent tablets based on solid dispersions of ...furazolidone in the form of an aqueous solution for external use.
Materials and methods.
The used substances were: furazolidone, anhydrous sodium carbonate (chemically pure), polyvinylpyrrolidone-24000±2000 (chemically pure), malic acid (analytically pure), tartaric acid (chemically pure), citric acid (chemically pure), sodium benzoate (chemically pure), ethyl alcohol 96% (chemically pure), purified water. Preparation of granulates is separate wet granulation in a fluidized bed (Mycrolab, BOSCH, Germany). Obtaining tablets is the process of pressing on a manual hydraulic test press (“PRG”, VNIR, Russia). The dependence of disintegration, abrasion capacity and crushing resistance on compacting pressure was investigated. Technological parameters of granulates, еру obtained effervescent tablets, shelf life and storage conditions were investigated according to the State Pharmacopoeia of the Russian Federation XIV
th
ed.
Results.
Two compositions of effervescent tablets containing solid dispersions of furazolidone as an active substance were obtained, which, when dissolved in 100 ml of water at room temperature (20°C), form a solution of furazolidone with a concentration of 0.004% in less than 5 minutes. The method of quantitative determination of the furazolidone content in the effervescent tablets was validated. A complex of physicochemical methods for the analysis of tablets was carried out. Quality standards have been developed. The developed compositions stability of instant tablets during storage during accelerated and long-term tests has been experimentally confirmed. The preliminary shelf life and storage conditions have been determined.
Conclusion.
The result of technological and chemical-pharmaceutical research is the creation and evaluation of the quality of a new instant furazolidone dosage form as effervescent tablet formulations.
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