Combinations of Piperine with Hydroxypropyl-β-Cyclodextrin as a Multifunctional System

Piperine is an alkaloid that has extensive pharmacological activity and impacts other active substances bioavailability due to inhibition of CYP450 enzymes, stimulation of amino acid transporters and P-glycoprotein inhibition. Low solubility and the associated low bioavailability of piperine limit its potential. The combination of piperine with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) causes a significant increase in its solubility and, consequently, an increase in permeability through gastrointestinal tract membranes and the blood–brain barrier. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) were used to characterize interactions between piperine and HP-β-CD. The observed physicochemical changes should be combined with the process of piperine and CD system formation. Importantly, with an increase in solubility and permeability of piperine as a result of interaction with CD, it was proven to maintain its biological activity concerning the antioxidant potential (2,2-diphenyl-1-picryl-hydrazyl-hydrate assay), inhibition of enzymes essential for the inflammatory process and for neurodegenerative changes (hyaluronidase, acetylcholinesterase, butyrylcholinesterase).     

Enhancement of the Magnetic Coupling in Exfoliated CrCl3 Crystals Observed by Low-Temperature Magnetic Force Microscopy and X-ray Magnetic Circular Dichroism

Magnetic crystals formed by 2D layers interacting by weak van der Waals forces are currently a hot research topic. When these crystals are thinned to nanometric size, they can manifest strikingly different magnetic behavior compared to the bulk form. This can be the result of, for example, quantum electronic confinement effects, the presence of defects, or pinning of the crystallographic structure in metastable phases induced by the exfoliation process. In this work, an investigation of the magnetism of micromechanically cleaved CrCl₃ flakes with thickness >10 nm is performed. These flakes are characterized by superconducting quantum interference device magnetometry, surface-sensitive X-ray magnetic circular dichroism, and spatially resolved magnetic force microscopy. The results highlight an enhancement of the CrCl₃ antiferromagnetic interlayer interaction that appears to be independent of the flake size when the thickness is tens of nanometers. The estimated exchange field is 9 kOe, representing an increase of ≈900% compared to the one of the bulk crystals. This effect can be attributed to the pinning of the high-temperature monoclinic structure, as recently suggested by polarized Raman spectroscopy investigations in thin (8–35 nm) CrCl₃ flakes.     

Microfluidic architectures for efficient generation of chemistry gradations in droplets

We demonstrate a strategy for construction of high-throughput microfluidic systems generating gradations of chemistry in micro-droplets. The productivity of the systems that we propose is limited only by the maximum rate of the droplet formation, and does not need to be limited by the rate of mixing. Multilayer polycarbonate chips transform two miscible input streams A and B into N streams of droplets, containing mixtures [A] _i , [B] _i . Exemplary devices generate linear ([B] _i  ∝ i) and logarithmic gradations (ln[B] _i  ∝ i). We also analyze the use of the same strategy for the generation of concentration gradation in the streams of droplets comprising mixtures of liquids of different viscosities. The devices preserve the required distribution of compositions, while allowing the volume of the droplets to be tuned over almost two orders of magnitude (i.e. between 3 and 80 nL).     

The Influence of the Particle Size on the Adhesion Between Ceramic Particles and Metal Matrix in MMC Composites

This study investigated the influence of the particle size on the adhesion force between ceramic particles and metal matrix in ceramic-reinforced metal matrix composites. The Cu-Al₂O₃ composites with 5 vol.% of ceramic phase were prepared by a powder metallurgy process. Alumina oxide powder as an electrocorundum (Al₂O₃) powder with different particle sizes, i.e., fine powder <3 µm and coarse powder of 180 µm was used as a reinforcement. Microstructural investigations included analyses using scanning electron microscopy with an integrated EDS microanalysis system and transmission microscopy. In order to measure the adhesion force (interface strength), we prepared the microwires made of the investigated materials and carried out the experiments with the use of the self-made tensile tester. We have observed that the interface strength is higher for the sample with coarse particles and is equal to 74 ± 4 MPa and it is equal to 68 ± 3 MPa for the sample with fine ceramic particles.     

Solid-state stability studies of faropenem based on chromatography,spectroscopy and theoretical analysis

Aim: The purpose of this study was to investigate the stability of faropenem in solid state.

Results: The kinetic and thermodynamic parameters of degradation of faropenem were studied using an RP-HPLC method while the changes of spectral properties were investigated using derivative UV and FT-IR. Quantum-chemical calculations, based on the density functional theory, were carried out to support the estimation of the intra-ring stresses of faropenem and for theoretical interpretation of the spectra. The degradation of faropenem was a first-order reaction depending on the substrate concentration at an increased relative humidity and in dry air. The dependence ln k = f(1/T) became the ln k?=?(2.03?±?3.22)?×?10⁴–(9761?±?3052)(1/T) in dry air and ln k?=?(1.25?±?0.22)?×?10⁵–(9004?±?3479)(1/T?) at 90.0% RH. The thermodynamic parameters E_a, ΔH^≠a, and ΔS^≠a of the degradation of faropenem were calculated. The dependence ln k?=?f(RH%) assumed the form ln k?=?(7.58?±?1.88)?×?10^?2 (RH%) – (5.90?±?3.90)?×?10^?8.

Conclusions: Stability studies of faropenem showed that the fusion of β-lactam and thiazolidine rings reduces the intra-ring stress, leading to a lower susceptibility to degradation in dry air and at increased RH.     

Sodium Butyrate Enhances Curcuminoids Permeability through the Blood-Brain Barrier,Restores Wnt/β-Catenin Pathway Antagonists Gene Expression and Reduces the Viability of Glioblastoma Cells

Glioblastoma (GBM) is an extremely aggressive brain tumor awaiting novel, efficient, and minimally toxic treatment. Curcuminoids (CCM), polyphenols from Curcuma longa, and sodium butyrate (NaBu), a histone deacetylase inhibitor naturally occurring in the human body, await elucidation as potential anti-GBM agents. Thus, the aim of this study was to analyze CCM and NaBu both separately and as a combination treatment using three GBM cell lines. MTT was used for cytotoxicity evaluation, and the combination index was calculated for synergism prediction. Cell cycle, apoptosis, and reactive oxygen species (ROS) generation were analyzed using flow cytometry. DNA methylation was verified by MS-HRM and mRNA expression by qPCR. The permeability through the blood-brain barrier (BBB) and through the nasal cavity was evaluated using PAMPA model. The results of this study indicate that CCM and NaBu synergistically reduce the viability of GBM cells inducing apoptosis and cell cycle arrest. These effects are mediated via ROS generation and changes in gene expression, including upregulation of Wnt/β-catenin pathway antagonists, SFRP1, and RUNX3, and downregulation of UHRF1, the key epigenetic regulator. Moreover, NaBu ameliorated CCM permeability through the BBB and the nasal cavity. We conclude that CCM and NaBu are promising agents with anti-GBM properties.     

New polyester biodegradable scaffolds for chondrocyte culturing: Preparation,properties, and biological activity

An innovative modification of the wet inversion phase method, consisting in the use of a polymer nano-nonwoven as a nonclassic pore precursor. Mechanical properties of the obtained scaffolds were determined, their hydrophilic properties (serum absorbability) were tested, and the content of residues of materials used in the scaffold preparation was determined. Nontoxicity of the developed scaffolds toward T lymphocyte cells was proved. Cultures of primary chondrocytes were obtained successfully. It was proved that an addition of a polymer nano-nonwoven changes the properties of the scaffolds favorably in respect of their subsequent application in tissue engineering.     

Effect of Chronic Administration of 5-(3-chlorophenyl)-4-Hexyl-2,4 -Dihydro-3H-1,2,4-Triazole-3-Thione (TP-315)—A New Anticonvulsant Drug Candidate—On Living Organisms

About 70 million people suffer from epilepsy—a chronic neurodegenerative disease. In most cases, the cause of the disease is unknown, but epilepsy can also develop as the result of a stroke, trauma to the brain, or the use of psychotropic substances. The treatment of epilepsy is mainly based on the administration of anticonvulsants, which the patient must most often use throughout their life. Despite significant progress in research on antiepileptic drugs, about 30% of patients still have drug-resistant epilepsy, which is insensitive to pharmacotherapy used so far. In our recent studies, we have shown that 4-alkyl-5-aryl-1,2,4-triazole-3-thiones act on the voltage-gated sodium channels and exhibit anticonvulsant activity in an MES (maximal electroshock-induced seizure) and 6Hz test in mice. Previous studies have shown their beneficial toxic and pharmacological profile, but their effect on a living organism during chronic use is still unknown. In the presented study, on the basis of the previously conducted tests and the PAMPA (parallel artificial membrane permeability assay) BBB (blood–brain barrier) test, we selected one 1,2,4-triazole-3-thione derivative—TP-315—for further studies aimed at assessing the impact of its chronic use on a living organism. After long-term administration of TP-315 to Albino Swiss mice, its effect on the functional parameters of internal organs was assessed by performing biochemical, morphological, and histopathological examinations. It was also determined whether the tested compound inhibits selected isoforms of the CYP450 enzyme system. On the basis of the conducted tests, it was found that TP-315 does not show nephrotoxic nor hepatotoxic effects and does not cause changes in hematological parameters. In vitro tests showed that TP-315 did not inhibit CYP2B6, CYP2D6, CYP3A4, or CYP3A5 enzymes at the concentration found in the serum of mice subjected to long-term exposure to this compound.     

Fabrication and Oxidation Resistance of TiAl Matrix Coatings Reinforced with Silicide Precipitates Produced by Heat Treatment of Warm Sprayed Coatings

Ti-Al-based intermetallics are promising candidates as coating materials for thermal protection systems in aerospace vehicles; they can operate just below the temperatures where ceramics are commonly used, and their main advantage is the fact that they are lighter than most other alloys, such as MCrAlY. Therefore, Ti-Al-Si alloy coatings with five compositions were manufactured by spraying pure Ti and Al-12 wt.% Si powders using warm spray process. Two-stage hot pressing at 600 and 1000 °C was applied to the deposits in order to obtain titanium aluminide intermetallic phases. The microstructure, chemical composition, and phase composition of the as-deposited and hot-pressed coatings were investigated using SEM, EDS, and XRD. Applying of hot pressing enabled the formation of dense coatings with porosity around 0.5% and hard Ti₅(Si,Al)₃ silicide precipitates. It was found that the Ti₅(Si,Al)₃ silicides existed in two types of morphologies, i.e., as large particles connected together and as small isolated particles dispersed in the matrix. Furthermore, the produced coatings exhibited good isothermal and cyclic oxidation resistance at a temperature of 750 °C for 100 h.     

Acid-base catalysis of N-[(morpholine)methylene]daunorubicin

The stability of N-[(morpholine)methylene]-daunorubicin hydrochloride (MMD) was investigated in the pH range 0.44-13.54, at 313, 308, 303 and 298 K. The degradation of MMD as a result of hydrolysis is a pseudo-first-order reaction described by the following equation: ln c = ln c(0) - k(obs)? t. In the solutions of hydrochloric acid, sodium hydroxide, borate, acetate and phosphate buffers, k(obs) = k(pH) because general acid-base catalysis was not observed. Specific acid-base catalysis of MMD comprises the following reactions: hydrolysis of the protonated molecules of MMD catalyzed by hydrogen ions (k(1)) and spontaneous hydrolysis of MMD molecules other than the protonated ones (k(2)) under the influence of water. The total rate of the reaction is equal to the sum of partial reactions: k(pH) = k(1) ? a(H)+ ? f(1) + k(2) ? f(2) where: k(1) is the second-order rate constant (mol(-1) l s(-1)) of the specific hydrogen ion-catalyzed degradation of the protonated molecules of MMD; k(2) is the pseudo-first-order rate constant (s(-1)) of the water-catalyzed degradation of MMD molecules other than the protonated ones, f(1) - f(2) are fractions of the compound. MMD is the most stable at approx. pH 2.5.