Hybrid cross‐linked hydrogels as a technology platform for in vitro release of cephradine

Hydrogel‐based drug delivery systems can leverage therapeutically favorable upshots of drug release and found clinical uses. Hydrogels offer temporal and spatial control over the release of different therapeutic agents. Because of their tailor made controllable degradability, physical properties, and ability to prevent the labile drugs from degradation, hydrogels provide platform on which diverse physicochemical interactions with entrapped drugs cause to control drug release. Herein, we report the fabrication of novel vinyltrimethoxy silane (VTMS) cross‐linked chitosan/polyvinyl pyrrolidone hydrogels. Swelling in distilled water in conjunction with different buffer and electrolyte solutions was performed to assess the swellability of hydrogels. Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X‐ray diffraction (XRD) analysis were further conducted to investigate the possible interactions between components, thermal stability, and crystallinity of as‐prepared hybrid hydrogels, respectively. In vitro time‐dependent biodegradability, antimicrobial study, and cytotoxicity were also carried out to evaluate their extensive biocompatibility and cytotoxic behavior. More interestingly, in vitro drug release study allowed for the controlled release of cephradine. Therefore, this facile strategy developed the novel biocompatible and biodegradable hybrid hydrogels, which could significantly expand the scope of these hydrogels in other biomedical applications like scaffolds, skin regeneration, tissue engineering, etc.     

Towards Multipotent Coatings: Chemical Vapor Deposition and Biofunctionalization of Carbonyl‐Substituted Copolymers

Future advances in designing bioactive materials, such as antithrombotic coatings for cardiovascular stents, will require widely applicable and robust methods of surface modification. In this paper, we report on the development of multifunctional polymer coatings made by chemical vapor deposition (CVD) copolymerization. Polymer coatings of various [2.2]paracyclophane derivatives were co‐deposited in controlled ratios and their chemical composition verified by FT‐IR and X‐ray photoelectron spectroscopy. Furthermore, preliminary biocompatibility of these coatings was assessed using human umbilical vein endothelial cells and 3T3 murine fibroblasts. The parallel immobilization of two different antithrombotic biomolecules onto a CVD‐based copolymer is also demonstrated by orthogonal immobilization strategies.

     

Optimization of extraction and quantification technique for phenolics content of garlic (Allium sativum): An application for comparative phytochemical evaluation based on cultivar origin

A range of conventional, i.e. maceration, percolation, ultrasonic assisted, Soxhlet and Soxtec extraction (STE), to advanced extraction techniques of accelerated solvent extraction (ASE) was utilized for the first time in order to optimize the extract yield and recovery of phenolics—gallic acid (GA), rutin (RT) and quercetin (QT)—quantified via ultra-high performance liquid chromatography with diode array detector (UHPLC–DAD). The effect of solvents (n-hexane, dichloromethane and methanol) and temperature (60, 80 and 100°C) upon extraction yield, phenolic content and antioxidant activity (DPPH, ABTS and DPPH) was studied, and the method was validated in commercial food samples from Saudi Arabia, China and India. A high extract yield with percentage recovery was observed for STE (1221.10 mg/5 g; 24.42%) and ASE techniques (91.50 mg/1 g; 9.15%) in methanol at 100°C. UHPLC–DAD showed retention times (min) of 0.67, 1.93 and 1.90 for GA, RT and QT, respectively in the shortest runtime of 3 min. The yield for phenolics was higher for STE/ASE (ppm): 15.27/15.29 (GA), 85.24/37.56 (RT) and 52.20/33.40 (QT), respectively. In terms of antioxidant activities, low IC₅₀ values (μg/ml) of 1.09/1.18 (DPPH), 2.11/5.32 (ABTS) and 4.35/7.88 (phenazine methosulfate–nicotinamide adenine dinucleotide) were observed for STE and ASE, respectively. Multivariate analysis for STE showed a significant (P = 0.000) correlation for extraction type vs. extract yield and phenolics content; however, there was no significance for antioxidant activities vs. extraction type. ASE showed a positive correlation for solvent vs. extraction yield, phenolics and antioxidant activity; however, there was no correlation for extraction yield and DPPH activity. Principal component analysis for STE showed a major variability (52.02%) for extraction yield and phenolics in PC1 followed by PC2 (38.30%) for antioxidant activities. For ASE, PC1 (48.68%) showed a positive correlation for solvent vs. extraction yield and phenolics while PC2 (33.12%) showed a positive correlation for temperature and antioxidant activities. STE and ASE were the optimized extraction techniques for the garlic food sample while a significant effect of solvent and temperature was observed upon extraction yield, phenolics and antioxidant activity.     

Small Ubiquitin-Like Modifier Protein 3 Enhances the Solubilization of Human Bone Morphogenetic Protein 2 in <Emphasis Type="Italic">E. coli</Emphasis>

Small ubiquitin-like modifier (SUMO) fusion technology is widely used in the production of heterologous proteins from prokaryotic system to aid in protein solubilization and refolding. Due to an extensive clinical application of human bone morphogenetic protein 2 (hBMP2) in bone augmentation, total RNA was isolated from human gingival tissue and mature gene was amplified through RT-PCR, cloned (pET21a), sequence analyzed, and submitted to GenBank (Accession no. KF250425). To obtain soluble expression, SUMO3 was tagged at the N-terminus of hBMP2 gene (pET21a/SUMO3-hBMP2), transferred in BL21 codon+, and ~?40% soluble expression was obtained on induction with IPTG. The dimerized hBMP2 was confirmed with Western blot, native PAGE analysis, and purified by fast protein liquid chromatography with 0.5 M NaCl elution. The cleavage of SUMO3 tag from hBMP2 converted it to an insoluble form. Computational 3D structural analysis of the SUMO3-hBMP2 was performed and optimized by molecular dynamic simulation. Protein-protein interaction of SUMO3-hBMP2 with BMP2 receptor was carried out using HADDOCK and inferred stable interaction. The alkaline phosphatase assay of SUMO3-hBMP2 on C2C12 cells showed maximum 200-ng/ml dose-dependent activity. We conclude that SUMO3-tagged hBMP2 is more suited for generation of soluble form of the protein and addition of SUMO3 tag does not affect the functional activity of hBMP2.     

One-pot synthesis of CuO/TiO2 nanocomposites for improved photocatalytic hydrogenation of 4-nitrophenol to 4-aminophenol under direct sunlight

The excellent photocatalytic hydrogenation of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) with NaBH₄ in the aqueous medium is still a big challenge. Herein, we report a facile one-pot evaporation-induced self-assembly (EISA) method to synthesize a series of CuO/TiO₂ nanocomposites. The as-synthesized CuO/TiO₂ photocatalysts exhibit remarkable catalytic activity under direct sunlight in selective hydrogenation of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) due to the synergistic interaction of guest copper nanoparticles with host titanium dioxide (TiO₂) species. Especially, 5 wt% CuO/TiO₂ nanocomposite revealed superior reaction rate constant (k) value (0.306 min⁻¹) when compared to 3 wt% CuO/TiO₂ (0.192 min⁻¹) and 7 wt% CuO/TiO₂ (0.240 min⁻¹). Moreover, several characterization techniques (XRD, TEM, N₂ adsorption–desorption isotherm, DRS, and XPS) were executed to deeply investigate the effect of copper content on the bulk and interfacial properties of the catalysts. The characterization results proved that the superior photocatalytic hydrogenation over 5 wt% CuO/TiO₂ catalyst can be ascribed to moderate CuO loading as well as even dispersion of CuO species on the surface of active TiO₂ host, which can largely improve the light absorption ability within visible light region. Besides, the 5 wt% CuO/TiO₂ catalyst exhibits remarkable recyclability and durability, retaining its superior activity (above 95%) up to several repeating cycles, proving its practical applicability for hydrogenation reactions at domestic and industrial levels.     

Structure-based design of Aurora A & B inhibitors

The Aurora family of serine/threonine kinases are mitotic regulators involved in centrosome duplication, formation of the bipolar mitotic spindle and the alignment of the chromosomes along the spindle. These proteins are frequently overexpressed in tumor cells as compared to normal cells and are therefore potential therapeutic oncology targets. An Aurora A high throughput screen revealed a promising sub-micromolar indazole-benzimidazole lead. Modification of the benzimidazole portion of the lead to a C2 linker with a phenyl ring was proposed to achieve novelty. Docking revealed that a conjugated linker was optimal and the resulting compounds were equipotent with the lead. Further structure-guided optimization of substituents on the 5 & 6 position of the indazole led to single digit nanomolar potency. The homology between the Aurora A & Aurora B kinase domains is 71% but their binding sites only differ at residues 212 & 217 (Aurora A numbering). However interactions with only the latter residue may be used for obtaining selectivity. An analysis of published Aurora A and Aurora B X-ray structures reveals subtle differences in the shape of the binding sites. This was exploited by introduction of appropriately sized substituents in the 4 & 6 position of the indazole leading to Aurora B selective inhibitors. Finally we calculate the conformational energy penalty of the putative bioactive conformation of our inhibitors and show that this property correlates well with the Aurora A binding affinity.     

Preparation of Ni–YSZ thin and thick films on metallic interconnects as cell supports. Applications as anode for SOFC

In this work, we propose the preparation of a duplex anodic layer composed of both a thin (100 nm) and a thick film (10 μm) with Ni–YSZ material. The support of this anode is a metallic substrate, which is the interconnect of the SOFC unit cell. The metallic support limits the temperature of thermal treatment at 800 °C to keep a good interconnect mechanical behaviour and to reduce corrosion. We have chosen to elaborate anodic coatings by sol–gel route coupled with dip-coating process, which are low cost techniques and allow working with moderate temperatures. Thin films are obtained by dipping interconnect substrate into a sol, and thick films into an optimized slurry. After thermal treatment at only 800 °C, anodic coatings are adherent and homogeneous. Thin films have compact microstructures that confer ceramic protective barrier on metal surface. Further coatings of 10 μm thick are porous and constitute the active anodic material.     

Activation of Platinum(IV) Prodrugs By Motexafin Gadolinium as a Redox Mediator

Water‐soluble platinum(IV) prodrugs, which proved kinetically stable to reduction in the presence of physiological concentration of ascorbate, were quickly reduced to their active form, oxaliplatin, when co‐incubated with a macrocycle metallotexaphyrin (i.e., Motexafin Gadolinium (MGd)). The reduction of Pt^IV to Pt^II promoted by MGd occurs in cell culture as well, leading to an increase in the antiproliferative activity of the Pt^IV species in question. The mediated effect is proportional to the concentration of MGd and gives rise to an enhancement when the prodrug is relatively hydrophilic. MGd is known to localize/accumulate preferentially in tumor tissues. Thus, the present “activation by reduction” approach may allow for the cancer‐selective enhancement in the cytotoxicity of Pt^IV prodrugs.     

Structural characterization of new Cd(2+) fluorescent sensor based on lumazine ligand: AM1 and ab initio studies

6-Thienyllumazine (TLM) is synthesized as a new fluorescent sensor that is capable of indicating selectively the presence of Cd(2+) ion via a fluorescence signal. Experiment has been performed in the presence of Ni(2+), Co(2+), Cu(2+), Ag(+), Mn(2+), Hg(2+), Zn(2+), Pb(2+), and Mg(2+) metal ions in aqueous solutions. The product was characterized by elemental analysis, mass, and NMR spectra. The spectral characteristics (maxima, quantum yields, Stokes shift, and lifetimes) of TLM in organic and aqueous solvents have been studied with the help of absorption and fluorescence spectroscopy, as well as, using time dependent spectrofluorimetry (single photon counting technique). The fluorescence dependence of TLM on the pH has also been investigated. The experimental results indicate that TLM exists in two ionic forms: neutral (acid) and anion (base). Electronic structure calculations of TLM were carried out using Semiempirical Austin Model 1 (AM1) and ab initio Hartree-Fock (HF) with 6-31G* basis set and using Gaussian 03 program. Absorption energies for TLM have been calculated using ZINDO method. The theoretical results confirm the presence of the thiophene and pteridine rings in two conformations: twisted at angle of about 35 degrees in the excited state and coplanar in the ground state.