Enzyme-Responsive Hydrogels as Potential Drug Delivery Systems—State of Knowledge and Future Prospects

Fast advances in polymer science have provided new hydrogels for applications in drug delivery. Among modern drug formulations, polymeric type stimuli-responsive hydrogels (SRHs), also called smart hydrogels, deserve special attention as they revealed to be a promising tool useful for a variety of pharmaceutical and biomedical applications. In fact, the basic feature of these systems is the ability to change their mechanical properties, swelling ability, hydrophilicity, or bioactive molecules permeability, which are influenced by various stimuli, particularly enzymes. Indeed, among a great number of SHRs, enzyme-responsive hydrogels (ERHs) gain much interest as they possess several potential biomedical applications (e.g., in controlled release, drug delivery, etc.). Such a new type of SHRs directly respond to many different enzymes even under mild conditions. Therefore, they show either reversible or irreversible enzyme-induced changes both in chemical and physical properties. This article reviews the state-of-the art in ERHs designed for controlled drug delivery systems (DDSs). Principal enzymes used for biomedical hydrogel preparation were presented and different ERHs were further characterized focusing mainly on glucose oxidase-, β-galactosidase- and metalloproteinases-based catalyzed reactions. Additionally, strategies employed to produce ERHs were described. The current state of knowledge and the discussion were made on successful applications and prospects for further development of effective methods used to obtain ERH as DDSs.     

Anti-Inflammatory and Antiviral Effects of Cannabinoids in Inhibiting and Preventing SARS-CoV-2 Infection

The COVID-19 pandemic caused by the SARS-CoV-2 virus made it necessary to search for new options for both causal treatment and mitigation of its symptoms. Scientists and researchers around the world are constantly looking for the best therapeutic options. These difficult circumstances have also spurred the re-examination of the potential of natural substances contained in Cannabis sativa L. Cannabinoids, apart from CB1 and CB2 receptors, may act multifacetedly through a number of other receptors, such as the GPR55, TRPV1, PPARs, 5-HT1A, adenosine and glycine receptors. The complex anti-inflammatory and antiviral effects of cannabinoids have been confirmed by interactions with various signaling pathways. Considering the fact that the SARS-CoV-2 virus causes excessive immune response and triggers an inflammatory cascade, and that cannabinoids have the ability to regulate these processes, it can be assumed that they have potential to be used in the treatment of COVID-19. During the pandemic, there were many publications on the subject of COVID-19, which indicate the potential impact of cannabinoids not only on the course of the disease, but also their role in prevention. It is worth noting that the anti-inflammatory and antiviral potential are shown not only by well-known cannabinoids, such as cannabidiol (CBD), but also secondary cannabinoids, such as cannabigerolic acid (CBGA) and terpenes, emphasizing the role of all of the plant’s compounds and the entourage effect. This article presents a narrative review of the current knowledge in this area available in the PubMed, Scopus and Web of Science medical databases.     

Synthesis of Novel Phosphonic‐Type Activity‐Based Probes for Neutrophil Serine Proteases and Their Application in Spleen Lysates of Different Organisms

Neutrophils are a type of granulocyte important in the “first line of defense” of the innate immune system. Upon activation, they facilitate the destruction of invading microorganisms by the production of superoxide radicals, as well as the release of the enzymatic contents of their lysozymes. These enzymes include specific serine proteases: cathepsin G, neutrophil elastase, proteinase 3, as well as the recently discovered neutrophil serine protease 4 (NSP4). Under normal conditions, the proteolytic activity of neutrophil proteases is tightly regulated by endogenous serpins; however, this mechanism can be subverted during tissue stress, thereby resulting in the uncontrolled activity of serine proteases, which induce chronic inflammation and subsequent pathology. Herein, we describe the development of low‐molecular‐weight activity‐based probes that specifically target the active sites of neutrophil proteases.     

High resolution SEM characterization of nano‐precipitates in ODS steels

The performance of the present‐day scanning electron microscopy (SEM) extends far beyond delivering electronic images of the surface topography. Oxide dispersion strengthened (ODS) steel is on of the most promising materials for the future nuclear fusion reactor because of its good radiation resistance, and higher operation temperature up to 750°C. The microstructure of ODS should not exceed tens of nm, therefore there is a strong need in a fast and reliable technique for their characterization. In this work, the results of low‐kV SEM characterization of nanoprecipitates formed in the ODS matrix are presented. Application of highly sensitive photo‐diode BSE detector in SEM imaging allowed for the registration of single nm‐sized precipitates in the vicinity of the ODS alloys. The composition of the precipitates has been confirmed by TEM‐EDS.     

Modification of TiAlV Alloys with Hybrid Layers Containing Metallic Nanoparticles Obtained by the Sol–Gel Method: Surface and Structural Properties

The aim of the work was to obtain hybrid coatings containing silver, copper, and zinc nanoparticles on the TiAlV medical alloy via a sol–gel process. The developed layers were designed to bring about a bactericidal and fungicidal effect, as well as for protection against surgical scratches during the implantation of implants used in veterinary medicine. In this work, the authors focused on evaluating the microstructure (SEM + EDS); the structure (XRD, FTIR); and the surface properties, such as wettability, free surface energy, and roughness of layers with various concentrations of metallic nanoparticles (2 and 5 mol %). Our results confirmed that the sol–gel method enables the easy manufacturing of hybrid layers endowed with different porosity values as well as various shapes and sizes of metallic nanoparticles. A higher concentration of nanoparticles was observed on the surface containing 5 mol % of metallic salts. The highest degree of homogeneity was obtained for the layers containing silver nanoparticles. In addition, the silver nanoparticles were round and had the smallest dimensions, even below 20 nm. The FTIR and XRD structural studies confirmed the presence of an organosilicon matrix containing all three types of the metallic particles. We conclude that the higher concentration of nanoparticles influenced the alloy surface parameters.     

The Combination of Intestinal Alkaline Phosphatase Treatment with Moderate Physical Activity Alleviates the Severity of Experimental Colitis in Obese Mice via Modulation of Gut Microbiota,Attenuation of Proinflammatory Cytokines,Oxidative Stress Biomarkers and DNA Oxidative Damage in Colonic Mucosa

Inflammatory bowel diseases (IBD) are commonly considered as Crohn’s disease and ulcerative colitis, but the possibility that the alterations in gut microbiota and oxidative stress may affect the course of experimental colitis in obese physically exercising mice treated with the intestinal alkaline phosphatase (IAP) has been little elucidated. Mice fed a high-fat-diet (HFD) or normal diet (ND) for 14 weeks were randomly assigned to exercise on spinning wheels (SW) for 7 weeks and treated with IAP followed by intrarectal administration of TNBS. The disease activity index (DAI), grip muscle strength test, oxidative stress biomarkers (MDA, SOD, GSH), DNA damage (8-OHdG), the plasma levels of cytokines IL-2, IL-6, IL-10, IL-12p70, IL-17a, TNF-α, MCP-1 and leptin were assessed, and the stool composition of the intestinal microbiota was determined by next generation sequencing (NGS). The TNBS-induced colitis was worsened in obese sedentary mice as manifested by severe colonic damage, an increase in DAI, oxidative stress biomarkers, DNA damage and decreased muscle strength. The longer running distance and weight loss was observed in mice given IAP or subjected to IAP + SW compared to sedentary ones. Less heterogeneous microbial composition was noticed in sedentary obese colitis mice and this effect disappeared in IAP + SW mice. Absence of Alistipes, lower proportion of Turicibacter, Proteobacteria and Faecalibacterium, an increase in Firmicutes and Clostridium, a decrease in oxidative stress biomarkers, 8-OHdG content and proinflammatory cytokines were observed in IAP + SW mice. IAP supplementation in combination with moderate physical activity attenuates the severity of murine colitis complicated by obesity through a mechanism involving the downregulation of the intestinal cytokine/chemokine network and oxidative stress, the modulation of the gut microbiota and an improvement of muscle strength.     

Two-stage method of obtaining high bulk density sodium tripolyphosphate: Design and mechanism of process

The paper presents a two-step method for obtaining sodium tripolyphosphate (STPP) with a bulk density of about 0.90 kg/dm³ after the first step, using sodium phosphates after spray drying and water as the raw materials. STPP with a bulk density of 0.95–1.00 kg/dm³ was generated in the second stage, using STPP from the first step and water as the raw materials. The paper presents statistical analyses to define the process parameters which significantly affect sodium tripolyphosphate bulk density. The determination of the profile approximation and utility function enabled the optimization of process parameters for obtaining a product with a bulk density of 0.95–1.00 kg/dm³. Mechanisms of increasing bulk density was indicated by studies on the microstructure of the product and phase transformation during the process. The data were empirically verified and satisfactory results were found.     

Effective elastic properties and residual stresses in directionally solidified eutectic Al<Subscript>2</Subscript>O<Subscript>3</Subscript>/YAG/ZrO<Subscript>2</Subscript> ceramics estimated by finite element analysis

Effective elastic properties and residual stresses were assessed in directionally solidified ternary eutectic ceramic, Al₂O₃/YAG/ZrO₂, by finite element analyses. A 3D finite element model was generated from a CT scan, representative of the microstructure and with a similar volume fraction. Effective elastic properties were calculated by numerical homogenisation. They highlight a quasi-isotropic behaviour of the ternary eutectic ceramics. Despite the difficulties to measure the strain, the dispersion observed in the results and the limited reliability of the materials properties, the results constitute a step towards a better understanding of the material behaviour. Thermal residual stresses induced by the manufacturing were also evaluated. Tensile residual stresses in yttria-stabilised zirconia and compressive residual stresses in YAG and alumina were highlighted. This evaluation also shed light on the influence of the phase morphology in the microstructure. Indeed, the computed spatial distribution of the residual stresses showed that they are different from one position to another due to the variation in phase morphology and also to material properties variability. Therefore, it is important when numerically assessing the thermomechanical properties to take into account the microstructure morphology as well as the variability of material properties.     

The Numerical Comparison of Heat Transfer in a Coated and Fixed Bed of an Adsorption Chiller

Ecological adsorption technology is becoming a focus of attention by industry due to the utilization of low grade thermal energy sources for cooling production. It can be a promising part of sustainable development concept of the global economy. Therefore, research aiming at improving their performance i.e. Coefficient of Performance (COP) by optimizing the construction of sorption beds with a built in heat exchanger system is crucial. The heat transfer characteristics between the bed of porous media (sorbent) and surface of the heat exchanger system determine the heating power of an adsorption chiller. The HP increase can be obtained by heat transfer intensification due to the increase in the thermal conductivity of the sorbent layer in the vicinity of the heat exchanger’s surface. The novel modification of the sorbent layer structure is proposed in the paper in order to improve the heat transfer processes in the heat exchanger boundary layer. The analysis of desorption process conditions in the parametric model of a coated and fixed adsorption bed design is presented in the paper. The computational fluid dynamics (CFD) with conjugate heat transfer analysis is used to determine the crucial input parameters (temperature distribution in the sorbent bed) for further analytical calculations. The commercial code Ansys Fluent was used to perform numerical simulations. The developed computational model consisted of three subdomains representing heating water, heat exchanger material (copper) and sorbent (silica gel). The comparison of a novel coated design and a conventional fixed bed is discussed in the paper. The numerical analysis is based on experimental thermal conductivity measurements of the sorbent layer in different configurations, which were performed using Laser Flash Method.     

On Stochastic Modeling of Interface Defects in Composite Materials

The article presents mathematical and computational research dealing with the problem of stochastic interface defects occurring in composite materials between their constituents. A mathematical model of the periodic composite with such defects is presented in detail, as well as probabilistic numerical methods enabling computational experiments which are shown in a further part of the text. The fiber-reinforced and laminated composite has been tested in numerical tests as well as the superconducting coil cable-four-component composite to verify how the structural defects considered, according to the model introduced, influence the static behavior of the composites analyzed. All the results obtained and discussed in the article are summarized in concluding remarks which show the directions of further model development, while numerous references enable the reader to study the problem further.