Microparticle Formation Research Articles

Кальцийфосфатные брушитные цементы из замещенного трикальцийфосфата Ca3(PO4)2, армированные силикатным стекловолокном

The reinforcement of reaction hardening phosphate materials (phosphate cements) for bone implants, based on isomorphically cation- (Na+, K+) and anion- (SiO44-, SO42-) substituted tricalcium phosphate (β and α-TCP, Ca3(PO4)2), that are reinforced with silicate (basalt-based) fiberglass, is considered. The obtained materials were characterized by the XRD and SEM methods, mechanical compression tests were carried out, the setting times of cements were determined, changes in the pH of the aqueous medium in contact with the cements under study were measured. Microstructure analysis has been shown that the surface of the reinforcing fiber in contact with the matrix of hardening cement is partially corroded with the formation of phosphate microparticles on it. By pH-metry it was found that the samples during prolonged contact with water do not significantly change the pH value of the aquatic environment, which remains in the nearly neutral range from 5 to 7.5, favorable for further biological tests.

In situ Formation of Polymer Microparticles in Bacterial Nanocellulose Using Alternative and Sustainable Solvents to Incorporate Lipophilic Drugs

Bacterial nanocellulose has been widely investigated in drug delivery, but the incorporation of lipophilic drugs and controlling release kinetics still remain a challenge. The inclusion of polymer particles to encapsulate drugs could address both problems but is reported sparely. In the present study, a formulation approach based on in situ precipitation of poly(lactic-co-glycolic acid) within bacterial nanocellulose was developed using and comparing the conventional solvent N-methyl-2-pyrrolidone and the alternative solvents poly(ethylene glycol), CyreneTM and ethyl lactate. Using the best-performing solvents N-methyl-2-pyrrolidone and ethyl lactate, their fast diffusion during phase inversion led to the formation of homogenously distributed polymer microparticles with average diameters between 2.0 and 6.6 µm within the cellulose matrix. Despite polymer inclusion, the water absorption value of the material still remained at ~50% of the original value and the material was able to release 32 g/100 cm2 of the bound water. Mechanical characteristics were not impaired compared to the native material. The process was suitable for encapsulating the highly lipophilic drugs cannabidiol and 3-O-acetyl-11-keto-β-boswellic acid and enabled their sustained release with zero order kinetics over up to 10 days. Conclusively, controlled drug release for highly lipophilic compounds within bacterial nanocellulose could be achieved using sustainable solvents for preparation.

INFLUENCE OF MICROENCAPSULATION PARAMETERS ON THE SIZE AND MORPHOLOGY OF MICROCAPSULES BY ECO-FRIENDLY SOLVENT EVAPORATION METHOD ORIENTED TO MEDICAL TEXTILES

Application of microcapsules in medical textile has been studied and commercially developed widely in recent years. The aim of this work was to propose an eco-friendly microencapsulation by solvent evaporation method that can contribute to the manufacture of medical textile products using microcapsules. Quillaja saponin was used as bio-sourced surfactant and ethyl acetate was used as the less toxic, non-halogenated organic solvent. The influences of saponin concentration, stirring speed during emulsification step and the volume of ethyl acetate used to saturate the aqueous phase before emulsification on the microcapsule size and morphology were investigated. The results showed that eudragit microcapsules of ibuprofen with diameter in range from 17 to 34 µm, which were suitable for medical textile applications, were successfully elaborated. The saponin concentration varied from 0.025 to 0.1 wt%. The stirring speed was changed from 700 to 600 rpm. The volume of ethyl acetate used in saturation step was 0, 8 and 12 ml. In the scope of investigation, the saponin concentration and the volume of ethyl acetate used in saturation step did affect the microcapsule size and morphology while the stirring speed did not. The saturation step really helped to reduce the formation of irregular microparticles and to narrow the size distribution, but the microcapsules became more porous, weaker and were deformed significantly by drying in the fabric treatment process.

Evaluation of subvisible particles in human immunoglobulin and lipid nanoparticles repackaged from a multi-dose vial using plastic syringes

The multi-dose vial (MDV) is widely used for most biopharmaceuticals that are repackaged in plastic syringes before use. However, subvisible particle formation with the use of plastic syringes containing silicone oil (SO syringes) for handling therapeutic proteins can be problematic. This study aimed to evaluate the extent of and trends in microparticle (>1 μm) formation and accumulation in repackaged syringes from MDVs containing human immunoglobulin (IgG) and lipid nanoparticles (LNPs). Light obscuration (LO) and flow imaging (FI) were used to analyze the microparticles. The number of microparticles observed with the use SO syringes was greater than that with SO-free syringes, and the number of microparticles continuously increased as did the number of times of repackaging in syringes for both drugs. However, a large variation was observed across different brands of SO syringes. In contrast, using a different technique of drug withdrawal from the vial significantly reduced the number of microparticles. Furthermore, the use of filter-integrated needles or the inclusion of stabilizers such as acetyl-arginine and Tween 20 into the formulation also helped reduce particle formation.

Artificial cerebrospinal fluid restores aspirin-inhibited physiological hemostasis through recovery of platelet aggregation function.

Optimal hemostasis provides safety and reliability during neurosurgery which improves surgical outcomes. Previously, artificial cerebrospinal fluid (aCSF) and its component sodium bicarbonate were found to facilitate physiological hemostasis by amplifying platelet aggregation. This study aimed to verify whether aCSF amplifies platelet-dependent hemostasis in the presence of antiplatelet agents. We prepared platelet-rich plasma (PRP) or washed platelets using aspirin (acetylsalicylic acid, (ASA)) or normal saline (NS). We evaluated samples treated with a commercially available aCSF solution or NS for amplification of aggregation, activation of integrin αIIbβ3, phosphatidylserine (PS) exposure, P-selectin (CD62P) expression, and formation of microparticles (MPs). We assessed the effect of aCSF on in vivo hemostasis in the presence of ASA by measuring the tail bleeding time in ASA-or NS-injected C57BL/6N mice. Compared with NS, aCSF amplified ASA-inhibited platelet aggregation by recovering platelet activation including PS exposure, MP release, CD62P expression, and integrin αIIbβ3 activation. When using washed platelets, aCSF almost completely counteracted the inhibition of platelet aggregation by ASA. Prolonged bleeding time from the amputated tail of ASA-injected mice was significantly shortened by the treatment with aCSF compared to NS. Sodium bicarbonate also directly amplified ASA-inhibited platelet aggregation. aCSF and sodium bicarbonate facilitate physiological hemostasis through the recovery of inhibited platelet aggregation even in the presence of ASA. The utilization of aCSF in the operative field may be advantageous for facilitating hemostasis in patients with impaired platelet function and contribute to improving outcomes of neurosurgery.

Effect of Water-Air Microemulsion of Flotation Agent Solution on Flotation of Polymetallic Sulfide Ores

The enrichment of polymetallic sulfide ore is a complex task. Fine grinding is carried out to reveal useful minerals, resulting in the formation of microparticles. It is difficult to achieve the floatation of microparticles and fine useful minerals are lost with flotation tailings. The problem of microparticle flotation can be solved by using air bubbles smaller than 50 µmin for the flotation process. Water-air microemulsion (WAME)of a frothersolution obtained using the generator was used as microbubbles. The effect of WAME on flotation was studied on polymetallic ores and gold-bearing ore from Kazakhstan deposits.The use of WAMEin the processing of polymetallic ore allowed for themaintenance of the quality of rougher concentrates, to increase the copper extraction in Cu-Pb rougherconcentrate by 7.41%, of lead by 5.98% in the copper-lead flotation cycle (Cu-Pb-Zn-Fe ore), copper extraction in Cu-Mo rougherconcentrate by 5.2%, and molybdenum by 4.7% in the copper-molybdenum flotation cycle (Cu-Mo ore). The indicators of flotation gold extraction into the gold-containing concentrate significantly improved in comparison with the basic mode when using the generator in rougher and scavenger flotation cycles: the quality increased by 5.3 g/t, and the extraction increased by 4.27%.

Dynamic Sickling Assay: Using Enzymatically Induced Hypoxia to Assess Real-Time Sickling Scalable from Large Erythrocyte Populations to Individual Cells

Background: There is a pressing need for assays to assess both patient condition and to monitor the progress of Sickle Cell Disease (SCD) therapies. It would be beneficial for an assay to allow assessment of oxygen dissociation, hemoglobin polymerization and Red Blood Cell (RBc) sickling under both equilibrium (mimicking longer-term effects) and non-equilibrium (simulating in-vivo process) conditions. Also desirable is the CLIA-waived system suitable for use in clinical trials and ultimately for clinical management of patients on SCD therapies including those those targeting Hb oxygen affinity. Our proposed work introduces an RBC hypoxia-induced sickling assay as a clinical tool to assess SCD patient condition and to assist in development, monitoring, and optimization of SCD therapies. Methods: The system uses an enzymatic oxygen scrubbing system allowing for a wide range of deoxygenation rates and final hypoxia severity. Diluted blood samples were supplemented with Protocatechuic acid (PCA) and then with Protocatechuate 3,4-Dioxygenase (PCD) enzyme inducing hypoxia at a predetermined rate. The sample was injected into an anaerobic microfluidic chamber with the resulting Red Blood Cell (RBC) morphological changes observed through time-lapsed photography. Image analysis allows for identification and quantification of sickled RBC linked to different polymerization scenarios/mechanisms. An oxygen probe was used to track the rate of medium deoxygenation. Sickling profiles were constructed to represent a percent of sickled RBC in a total cell population measured every two seconds after the enzymatic reaction is initiated. Profiles were assessed though i) percent sickling at normoxia, ii) morphological Point of Sickling (mPoS) and iii) time delay of sickling both measured at 5% increase in sickling over the normoxia sickling baseline, iv rate of sickling, v) size of the sickling fraction and vi) Area under the Curve (AUC). The last four parameters are measured for each sickling fraction if more than one such is present. Results: In control experiments PCA/PCD system was shown to allow reliable and reproducible sample deoxygenation currently enabled in a range from seconds to hours. Comprehensive multidimensional profiles were constructed presenting fraction of sickled RBC as a function of a) time from enzymatic reaction initiation, and b) one or more of rate of oxygen consumption, end of reaction hypoxia level, or oxygen tension in the medium. Such profiling allows for fast optimization of assay parameters to target assay conditions most suitable for detection of desired effects.Significant changes in sickling profiles, with marked delay in sickling, were observed upon treatment of RBC with hemoglobin-modifying drugs like voxelotor.Sickling profiles of Sickle Trait (SCT) patients showed significant delay in sickling compared to SS-type SCD patients. The method shows the potential to differentiate SCT patients based on the risk of adverse conditions to occur due to the patient's trait status.By stopping the flow, the system allows tracking of morphological status of individual cells over the full course of medium deoxygenation. Individual cells show pronounced differences in their propensity to sickle, potentially correlated to individual cell Hb F content. Change in morphology of sickling cells from biconcave disk to crescent and then to holly leaf and granular forms had been observed upon progressively decreasing medium oxygen tension.RBC microparticle formation can be observed and tracked over time as an additional metric of erythrocyte response to developing hypoxia Conclusions: By using enzymatically induced hypoxia in a microfluidic environment, presented system allows comprehensive analysis of RBC sickling dynamics in a wide range of deoxygenation rates and conditions. It would find utility in SCD therapy development by offering a robust and high throughput method for assessing critical RBC response to therapies. With no need for cumbersome gas cylinders and low training requirements, a stand-alone system with single use disposable cartridges would also have utility in clinical trials both in the US and abroad, due to simplicity of use suitable for developing countries with limited infrastructure. When validated, the system can be adapted for Point of Care use either as complementary to other blood tests or in an independent monitoring mode.

A comprehensive investigation on the sorption of U(VI) and Eu(III) by polyamide microplastics: Surface-assisted microparticle formation

The sorption of Eu(ΙΙΙ) and U(VI) on microplastics (MP) has been investigated at pH 4 and increased metal ion concentrations ([Eu(ΙΙΙ)], [U(VI)] ≤ 1 mmol). The sorption studies have been carried out in batch type experiments and the characterisation of MP prior and after metal ion sorption was performed by FTIR and Raman, and Fluorescence (FS) and X-ray photoelectron (XPS) spectroscopy, ζ-potential measurements and SEM-EDS. The data clearly indicate that up to a certain concentration the metal ion sorption occurs via electrostatic interaction resulting in a surface charge neutralization and further metal ion concentration results in surface precipitation in the form of microparticles. The uranium microparticles have a well defined crystalline structure whereas in the case of europium amorphous particles are formed. The formation of microparticles on the MP surfaces is of cardinal importance regarding both, the preparation of a new type of microparticles as well as the environmental impact of such microparticle structures.

On the influence of protein aggregate sizes for the formation of solid and hollow protein microparticles

Microparticles can function as carriers of e.g. pharmaceuticals and food ingredients. Hollow microparticles can enhance the capacitance due to their large interior void. For preparing microparticles, polymers have been assembled into spherical structures through the use of porous CaCO3 templates, followed by polymer cross-linking and selective template removal. However, this often results in the formation of microparticles with a solid core. Here we use proteins with different aggregate size distributions (<10 nm or >100 nm) to either form solid or hollow microparticles. Proteins were mixed with CaCl2 and Na2CO3 solutions, which from CaCO3 microcrystals (with 20–60 nm pores) with encapsulated proteins. Here it will be shown that small protein aggregates uniformly distributed into the CaCO3 templates. However, larger protein aggregates accumulated at the template edges. Au3+ ions were then added, which oxidize and cross-link proteins and are reduced to form gold nanoparticles (AuNPs). After removal of the templates, the small proteins formed solid microparticles and the larger protein aggregates hollow microparticles. This method of fabrication of solid and hollow protein microparticles, with embedded AuNPs, could be used for generating biomaterials with a broader range of applications, such as hosting molecules and multimodal imaging due to the presence of the AuNPs.

Controlled Fabrication of Carbon Nanotube Microspheres from Emulsion Templates: Exploring the Dynamics of Solvent Loss and Nanoparticle Assembly

AbstractThe use of emulsions as templates for nanomaterial assembly is a versatile method to create controlled microstructures. However, production rates are often low, particularly where the droplet phase solvent must be removed to achieve consolidation. Here, the emulsion templated fabrication of microparticles from multi‐walled carbon nanotubes (CNTs) is studied. As an exemplar primary nanoparticle for microparticle assembly, CNTs present particular challenges due to their strong inter‐particle interactions and limited dispersion in solvents. Nevertheless, small batches of CNT microparticles have demonstrated promising performances in energy storage, environmental remediation, and sensing due to their controlled structures. Improving CNT microparticle production through emulsion processing is therefore interesting to promote these real‐world applications. In this work, it is shown that the slow rate of CNT microparticle formation from water‐in‐oil emulsions is due to spontaneous emulsification. Then methanol‐in‐oil emulsions are tested, which rapidly form fragile CNT capsules. Using mixtures of methanol and water, a faster rate of solvent loss can be balanced alongside nanoparticle assembly; CNT microparticle formation is up to twice as fast using 40% methanol compared to aqueous dispersions. In addition to facilitating faster CNT microparticle production, these findings offer more broadly applicable insights into the mechanisms of solvent transport in emulsions.

Microfluidic formation of biodegradable PCLDA microparticles as sustainable sorbents for treatment of organic contaminants in wastewater

Polymeric microparticles (MPs) have attracted remarkable interest in environmental remediation owing to their economic benefits, simple manipulation and recyclability. However, most polymeric MPs have intrinsic issue for microplastic pollution, which can only be resolved for different materials using a biodegradable polymer. Here, we synthesize the photocurable polycaprolactone diacrylate (PCLDA) via an acrylation reaction for use as a sustainable sorbent in the treatment of organic contaminants. PCLDA can form chemically interconnected network, ensuring a solid state with the swelling phenomenon in their organic solvent. Using a flow-focusing droplet generator, we generate monodisperse oil-in-water (O/W) emulsions with the PCLDA solution as the oil dispersed phase and form MPs via in situ photopolymerization under UV light. Compared to the general solvent evaporation method, PCLDA MPs are found to have a fine morphology and narrow size distribution. We also evaluate the degree of swelling behavior of PCLDA MPs in various solvents based on their solubility parameter. Further we demonstrate that these PCLDA particles, as sustainable organic sorbents, exhibit high performance in the treatment of toluene oil droplets and solutes from water with good recyclability.

Synthesis, characterization, and photocatalytic applications of novel sword-like copper oxide microparticles

• Novel CuO microparticles in sword-like morphology were prepared by microemulsion and calcination. • The major composition of the prepared materials was confirmed by XRD and EDS. • The photocatalytic property of the CuO microparticles was established using methylene blue model dye compound. • The degradation of methylene blue dye followed first-order kinetic model according to the general Langmuir–Hinshelwood mechanism. This letter aimed to synthesize novel copper oxide (CuO) microparticles via the microemulsion method followed by calcination. The synthesized material was characterized by scanning electron microscopy, energy dispersive spectroscopy, X-ray diffractometry, and diffuse reflectance spectroscopy techniques; and subsequently applied for the degradation of methylene blue (MB) using the heterogeneous photo-Fenton method. SEM images revealed the formation of homogeneous sword-like CuO microparticles. The XRD pattern and EDS spectrum confirmed that the main part of the material was CuO with the formation of Na 8 Cu 5 O 10 as an impurity. The photocatalytic degradation of MB followed the first-order kinetic model according to the general Langmuir–Hinshelwood mechanism. The as-prepared materials can be successfully applied in the visible-light-induced photocatalytic degradation of hazardous organic compounds and industrial wastewaters.

Microfluidic Generation of Therapeutically Relevant Polycaprolactone (PCL) Microparticles: Computational and Experimental Approaches

Drug releasing microparticles play an important role in drug delivery as they can be used for site specific delivery as well as control over the release time of therapeutics. The use of microfluidic technologies for the fabrication of these particles is of increasing interest since they provide enhanced control over microparticle size and size distribution compared to bulk production methods. However, the use of microfluidic platforms in the production of drug releasing microparticles with therapeutically relevant cargo still requires optimization depending on their application, and the effect of the addition of cargo on the production process is still unexplored. Here we show the formation of therapeutically relevant (in terms of size and dose of cargo) polycaprolactone (PCL) microparticles using a microfluidic platform and analyze the effect of the addition of cargo in the microparticle size and size distribution. This microfluidic platform was designed with the aid of computational fluid dynamic simulations, allowing us to construct a polydimethylsiloxane (PDMS) microfluidic device capable of making microparticles in the range of 15 to 35 μm with low coefficient of variation (CV) both with and without cargo by varying the flow rate ratios of the phases used during droplet generation. Our data show the effect of the addition of cargo on the droplet and microparticle sizes and monodispersity. Our fabrication method allows the formation of spherical microparticles, optimal for biomedical applications. In addition, our microfluidic platform can maintain the generation of monodisperse droplets (with an average size of 52.5 μm) over extended periods of time, suggesting it has the capacity to be used for scaled-up production of PCL microparticles. This microfluidic device is a robust and reliable method for the fabrication of PCL microparticles with cargo, which can potentially be loaded with other relevant therapeutic molecules for biomedical applications.

Implications of particle size on the respective solid-state properties of naltrexone in PLGA microparticles

A thorough understanding of the complexities in formulating and manufacturing polymeric microspheres is required for new and generic drug applications. Specifically, for an ANDA application for polymeric microsphere-based products, the applicant must meet Q1 (qualitative) and Q2 (quantitative) sameness, and in some cases, Q3 (e.g., microstructural) sameness. Herein, we report the naltrexone crystallinity in a PLGA microparticle system prepared from a dichloromethane-benzyl alcohol solvent system results in a crystallinity dependence as a function of microparticle size from the same batch – illustrating intrabatch microstructural variability. As the particle size increases, the crystallinity increases, with additional polymorphic forms more readily noted at the large particle sizes. Furthermore, during dissolution, a polymorphic transition and/or crystallization occurs at larger size fractions. This study highlights the importance of controlling the manufacturing parameters during microparticle formation, specifically solvent extraction and particle size control. Furthermore, with the approval of generic microparticles formulations on the horizon, this study highlights the importance of Q3, the same components in the same concentration with the same arrangement of matter, whereby microparticles can have varying microstructural properties across particle sizes from the same batch.

Self-transformation of solid CaCO3 microspheres into core-shell and hollow hierarchical structures revealed by coherent X-ray diffraction imaging.

The self-transformation of solid microspheres into complex core-shell and hollow architectures cannot be explained by classical Ostwald ripening alone. Here, coherent X-ray diffraction imaging and 3D X-ray fluorescence were used to visualize in 3D the formation of hollow microparticles of calcium carbonate in the presence of polystyrene sulfonate (PSS). During the dissolution of the core made from 10-25 nm crystals, the shell developed a global spheroidal shape composed of an innermost layer of 30 nm particles containing high PSS content on which oriented vaterite crystals grew with their c axis mainly oriented along the meridians. The stabilizing role of PSS and the minimization of the intercrystal dipolar energy can explain in combination with Ostwald ripening the formation of these sophisticated structures as encountered in many systems such as ZnO, TiO2, Fe2O3, Co3O4, MnO2, Cu2O, ZnS, CaCO3 and Ca8H2(PO4)6·5H2O.

Four-Level Structural Hierarchy: Microfluidically Supported Synthesis of Polymer Particle Architectures Incorporating Fluorescence-Labeled Components and Metal Nanoparticles.

Hierarchical assemblies of functional polymer particles are promising due to their surface as well as physicochemical properties. However, hierarchical composites are complex and challenging to form due to the many steps necessary for integrating different components into one system. Highly structured four-level composite particles were formed in a four-step process. First of all, gold (Au) nanoparticles, poly(methyl methacrylate) (PMMA) nanoparticles, and poly(tripropylene glycol diacrylate) (poly-TPGDA) microparticles were individually synthesized. By applying microfluidic techniques, polymer nano- and microparticles were formed with tunable size and surface properties. Afterwards, the negatively charged gold nanoparticles and PMMA particles functionalized with a positively charged surface were mixed to form Au/PMMA assemblies. The Au/PMMA composites were mixed and incubated with poly-TPGDA microparticles to form ternary Au/PMMA/poly-TPGDA assemblies. For the formation of composite-containing microparticles, Au/PMMA/poly-TPGDA composites were dispersed in an aqueous acrylamide-methylenebisacrylamide solution. Monomer droplets were formed in a co-flow microfluidic device and photopolymerized by UV light. In this way, hierarchically structured four-level composites consisting of four different size ranges─0.025/0.8/30/1000 μm─were obtained. By functionalizing polymer nano- and microparticles with different fluorescent dyes, it was possible to visualize the same composite particle under two different excitation modes (λex = 395-440 and λex = 510-560 nm). The Au/PMMA/poly-TPGDA composite-embedded polyacrylamide microparticles can be potentially used as a model for the creation of composite particles for sensing, catalysis, multilabeling, and biomedical applications.

Hollow Silica Microparticles Based on Amphiphilic Polyphosphazenes.

Hollow microparticles are important materials, offering a larger surface area and lower density than their solid counterparts. Furthermore, their inner void space can be exploited for the encapsulation and release of guest species in a variety of applications. Herein, we present phosphazene-based silica hollow microparticles prepared via a surfactant-free sol-gel process through self-assembly of the alkoxysilyl-containing polymer in water–ethanol solution. Solely, a silane-derived polyphosphazene was used as the precursor for the microparticle formation, without additional classical silica sources. These novel hollow silica-based microparticles were prepared without surfactant, using a designed amphiphilic polyphosphazene for the particle formation made by two components, a hydrophilic unit consisting of 3-mercaptopropyl(trimethoxysilane), and a hydrophobic unit (dodecanethiol) attached to the double bonds from the poly(allylamine)phosphazene backbone via a thiol-ene photoreaction. Due to these two functionalities, a “vesicle”-like self-assembled structure was formed in the reaction medium, which could be then utilized for the microparticle preparation. The influence of NaOH during the synthesis was shown to affect the size and the wall thickness of the microparticles. This effect may enhance the possibilities to tailor such microparticles for drug delivery purposes or for future controlled release of other substances, such as drugs, fragrances, or anticorrosive pigments.

Experimental pastes containing niobophosphate and 45S5 bioactive glasses for treatment of dentin hypersensitivity: dentin permeability and tubule obliteration.

This study tested the ability of bioactive pastes containing niobophosphate and 45S5 glasses to reduce dentin permeability and to obliterate dentinal tubules, as a mean of reducing human dentin hypersensitivity. Experimental pastes with concentrations of 10, 20, and 30 wt% of two bioactive glasses (45S5 or niobophosphate [NbG]) were formulated. A paste without bioactive glass (placebo) and a commercial paste (Nano P, FGM) were used as controls. Forty dentin disc specimens were obtained from caries-free extracted third human molars and divided in 8 groups (n = 5). Percentage of permeability (%Lp) was assessed in a dental permeability machine considering hydraulic conductance, immediately after pastes application and at day 7, day 14, and day 21. The precipitates formed on the surface of the dentin discs (and dentinal tubules) were analyzed by SEM/EDS and micro-Raman spectra. Data of dentin permeability (%) 2-way repeated-measures (ANOVA) and Holm-Sidak post-tests (α = 0.05). Dentinal tubule obliteration was visually (and elemental) evaluated and descriptively reported. The experimental bioactive glass pastes containing NbG and 45S5, regardless of the concentration, reduced dentin permeability in comparison with pastes without bioactive glasses (P < 0.05). The formulated placebo and commercial paste did not reduce permeability over time (P < 0.05). SEM/EDS and micro-Raman analyses showed that both type of bioactive pastes (NbG or 45S5-based) presented mineral precipitates obliterating the dentinal tubules at day 21. NbG seems to offer a better initial effect than 45S5, while at 21 days there is no difference between both glasses. Experimental bioactive pastes containing NbG and 45S5 (at concentrations of 10%, 20%, or 30%) have potential to reduce dentin permeability (over time) in comparison with pastes without bioactive glasses; and this occurs on behalf of obliteration of dentinal tubules by microparticle and precipitate formation. Bioactive pastes containing NbG and 45S5 may benefit patients presenting dentin hypersensitivity, because these pastes can start acting fast after application and maintain their action up to 21 days.

Markers of hemostasis activation and endothelial damage in patients with active cancer

Introduction. Increased expression of tissue factor by tumor cells, formation of procoagulant microparticles and secretion of proinflammatory cytokines that activate leukocytes and endothelial cells are considered to be the main factors provoking blood coagulation activation in cancer patients.The aim of the investigation was to study the peculiarities of hemostasis activation markers and endothelial damage in patients with active cancer.Materials and methods. Patients with active cancer were included in the study. We determined the following biomarkers: fibrinogen (Fg), von Willebrand factor (vWF), D-dimer (D-d), growth differentiation factor 15 (GDF-15), vascular endothelial growth factor A (VEGF-A).Results. Twenty-two patients with active cancer were included in the study. The median follow-up of the patients was 180 days (minimum 90, maximum 240). The presence of metastatic lesion was found in 62% of patients. At the end of the follow-up period (after 6 months) remission of the underlying disease was observed in 45.5% of patients, and 54.5% of patients were found to have progressed oncoprocess. GDF-15 levels ranged from 1486 to 11,722 pg/ml and were above normal values in all patients. Significant variability was also revealed in the level of VEGF-A - from 1 to 2944 pkg/ml, and only in 7 (32%) patients its level corresponded to normal values (0-66 pkg/ml). High levels of Fg (&gt;3.6 g/L), D-d (&gt;500 ng/ml), and vWF (&gt;160%) were detected in 19 (86%), 18 (82%), and 17 (77%) patients, respectively.Conclusions. The pilot study demonstrates a pronounced activation of the blood coagulation system and endothelial damage in patients with active cancer receiving chemotherapy and having a high risk of venous thromboembolic complications. The detected relationship of markers characterizing blood coagulation activation (D-d) and endothelial damage (vWF) with the progression of oncoprocess necessitates their further study in this category of patients.

Correlation of laboratory markers of hemostatic system activation with concentration and size of plasma extracellular microparticles in patients with COVID-19

Introduction. In recent years, much attention has been paid to the study of extracellular microparticles (microvesicles and exosomes) and their role in the pathogenesis of human diseases.The objective of this study was to determine the number and size of plasma extracellular microparticles (PEMP) in patients with severe and extremely severe COVID-19 and correlate these data with the markers of hemostasis activation, inflammation, and tissue damage.Methods and Materials. The study included 29 patients with severe and extremely severe COVID-19. Concentration and size of PEMP were determined by nanoparticle trajectory analysis (NTA). All patients underwent the complete blood count and the thromboelastometry (TEM). Hemostatic, biochemical, and immunological parameters were assessed including fibrinogen, prothrombin time, activated partial thromboplastin time, D-dimer, C-reactive protein, lactate dehydrogenase, procalcitonin, von Willebrand factor antigen, interleukin 6, and interleukin 18.Results. There were 14 patients (48.3 %) discharged from the ICU with improvement (group 1— survived patients), and 15 patients (51.7 %) with lethal outcomes (group 2 — lethal outcome); the PEMP concentration did not differ between these groups. In group 2, there were heterogeneity of PEMP population, and a tendency to the larger PEMP size (p=0.074). In all patients, the PEMP concentration correlated negatively with both prothrombin time and the number of large platelets; the size of PEMP correlated negatively with the level of von Willebrand factor antigen, and positively with the fibrinogen. In group 1, the PEMP concentration had a direct correlation with both the level of interleukin 18 and maximum clot lysis in TEM; the PEMP size had a direct correlation with the maximum clot lysis in TEM and an inverse correlation with both the level of procalcitonin and maximum clot density in TEM.Conclusion. Our study confirms the importance of the process of extracellular microparticles formation in the COVID-19 pathogenesis. Our findings are consistent with the hypothesis that the parameters of PEMP population can be predictive biomarkers of the COVID-19 severity.