Novasomes as Nano-Vesicular Carriers to Enhance Topical Delivery of Fluconazole: A New Approach to Treat Fungal Infections

The occurrence of fungal infections has increased over the past two decades. It is observed that superficial fungal infections are treated by conventional dosage forms, which are incapable of treating deep infections due to the barrier activity possessed by the stratum corneum of the skin. This is why the need for a topical preparation with advanced penetration techniques has arisen. This research aimed to encapsulate fluconazole (FLZ) in a novasome in order to improve the topical delivery. The novasomes were prepared using the ethanol injection technique and characterized for percent entrapment efficiency (EE), particle size (PS), zeta potential (ZP), drug release, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and antifungal activity. The FN7 formulation with 94.45% EE, 110 nm PS and −24 ZP proved to be the best formulation. The FN7 formulation showed a 96% release of FLZ in 8 h. FTIR showed the compatibility of FLZ with excipients and DSC studies confirmed the thermal stability of FLZ in the developed formulation. The FN7 formulation showed superior inhibition of the growth of Candida albicans compared to the FLZ suspension using a resazurin reduction assay, suggesting high efficacy in inhibiting fungal growth.     

Electrochemical water splitting using nano-zeolite Y supported tungsten oxide electrocatalysts

Zeolites are often used as supports for metals and metal oxides because of their well-defined microporous structure and high surface area. In this study, nano-zeolite Y (50–150 nm range) and micro-zeolite Y (500–800 nm range) were loaded with WO₃, by impregnating the zeolite support with ammonium metatungstate and thermally decomposing the salt thereafter. Two different loadings of WO₃ were studied, 3 wt.% and 5 wt.% with respect to the overall catalyst. The prepared catalysts were characterized for their morphology, structure, and surface areas through scanning electron microscope (SEM), XRD, and BET. They were further compared for their electrocatalytic activity for hydrogen evolution reaction (HER) in 0.5 M H₂SO₄. On comparing the bare micro-zeolite particles with the nano-form, the nano-zeolite Y showed higher currents with comparable overpotentials and lower Tafel slope of 62.36 mV/dec. WO₃ loading brought about a change in the electrocatalytic properties of the catalyst. The overpotentials and Tafel slopes were observed to decrease with zeolite-3 wt.% WO₃. The smallest overpotential of 60 mV and Tafel slope of 31.9 mV/dec was registered for nano-zeolite with 3 wt.% WO₃, while the micro-zeolite gave an overpotential of 370 mV and a Tafel slope of 98.1 mV/dec. It was concluded that even with the same metal oxide loading, nano-zeolite showed superior performance, which is attributed to its size and hence easier escape of hydrogen bubbles from the catalyst.     

Label‐Free Photoelectrochemical Detection of Double‐Stranded HIV DNA by Means of a Metallointercalator‐Functionalized Electrogenerated Polymer

The design of photoactive functionalized electrodes for the sensitive transduction of double‐stranded DNA hybridization is reported. Multifunctional complex [Ru(bpy‐pyrrole)₂(dppn)]²⁺ (bpy‐pyrrole=4‐methyl‐4′‐butylpyrrole‐2,2′‐bipyridine, dppn=benzo[i]dipyrido[3,2‐a:2′,3′‐c]phenazine) exhibiting photosensitive, DNA‐intercalating, and electropolymerizable properties was synthesized and characterized. The pyrrole groups undergo oxidative electropolymerization on planar electrodes forming a metallopolymer layer on the electrode. Thanks to the photoelectrochemical and intercalating properties of the immobilized Ru^II complex, the binding of a double‐stranded HIV DNA target was photoelectrochemically detected on planar electrodes. Photocurrent generation through visible irradiation was correlated to the interaction between double‐stranded DNA and the metallointercalator polymer. These interactions were well fitted by using a Langmuir isotherm, which allowed a dissociation constant of 2×10⁶ L mol^?1 to be estimated. The low detection limit of 1 fmol L^?1 and sensitivity of 0.01 units per decade demonstrate excellent suitability of these modified electrodes for detection of duplex DNA.     

Nitrile functionalized silver(I) <Emphasis Type="Italic">N</Emphasis>-heterocyclic carbene complexes: DFT calculations and antitumor studies

A series of aliphatic nitrile functionalized benzimidazolium salts and their respective mononuclear N-heterocyclic carbene Ag(I)-NHC complexes are reported. The benzimidazolium salts were synthesized by N-alkylation of 1H-benzimidazole with an appropriate alkyl bromide, followed by reaction with either 5-bromovaleronitrile or 6-bromohexanenitrile. The respective mononuclear Ag(I)-NHC complexes were prepared by the reaction of the benzimidazolium salts with Ag₂O. All the synthesized compounds were characterized by physico-chemical and spectroscopic techniques. The molecular structures of the two complexes were elucidated through single-crystal X-ray diffraction analyses. Density functional theory was used to model the structures of the other complexes. The benzimidazolium salts and their complexes were screened for cytotoxicity against a breast cancer cell line (MCF-7), using the MTT assay. All the Ag(I)-NHC complexes gave IC₅₀ values ranging from 7.0 ± 1.06 to 12.9 ± 1.55 µM which are comparable to the standard drug, tamoxifen (IC₅₀ = 11.2 ± 1.84 µM), while all of the benzimidazolium salts proved to be inactive.     

Synthesis of new derivatives of thieno[2,3‐b]pyridine fused with octyl ring

Derivatives of thiophene, thieno[2,3‐b]pyridine, thieno[5′,4′:4,5]pyrimido[3,2‐a]pyridine and thiepine fused with octyl ring have been synthesized and tested for antimicrobial and antifungal activities. The structure of the newly synthesized compounds have been established on the basis of their analytical and spectral data.     

Models of the iron-only hydrogenase: Reactions of [Fe2(CO)6(μ-pdt)] with small bite-angle diphosphines yielding bridge and chelate diphosphine complexes [Fe2(CO)4(diphosphine)(μ-pdt)]

Reactions of [Fe₂(CO)₆(μ-pdt)] (1) (pdt = SCH₂CH₂CH₂S) and small bite-angle diphosphines have been studied. A range of products can be formed being dependent upon the nature of the diphosphine and reaction conditions. With bis(diphenylphosphino)methane (dppm), thermolysis in toluene leads to the formation of a mixture of bridge and chelate isomers [Fe₂(CO)₄(μ-dppm)(μ-pdt)] (2) and [Fe₂(CO)₄(κ²-dppm)(μ-pdt)] (3), respectively. Both have been crystallographically characterised, 3 being a rare example of a chelating dppm ligand in a first row binuclear system. At room temperature in MeCN with added Me₃NO · 2H₂O, the monodentate complex [Fe₂(CO)₅(κ¹-dppm)(μ-pdt)] (4) is initially formed. Warming 4 to 100 °C leads the slow conversion to 2, while oxidation (on alumina) gives [Fe₂(CO)₅(κ¹-dppmO)(μ-pdt)] (5). With bis(dicyclohexylphosphino)methane (dcpm), heating in toluene cleanly affords [Fe₂(CO)₄(μ-dcpm)(μ-pdt)] (6). With Me₃NO · 2H₂O in MeCN the reaction is not clean as the phosphine is oxidised but monodentate [Fe₂(CO)₅(κ¹-dcpm)(μ-pdt)] (7) can be seen spectroscopically. With 1,2-bis(diphenylphosphino)benzene (dppb) and cis-1,2-bis(diphenylphosphino)ethene (dppv) the chelate complexes [Fe₂(CO)₄(κ²-dppb)(μ-pdt)] (8) and [Fe₂(CO)₄(κ²-dppv)(μ-pdt)] (9), respectively are the final products under all conditions, although a small amount of [Fe₂(CO)₅(κ²-dppvO)(μ-pdt)] (10) was also isolated. Protonation of 2 with HBF₄ affords a cation with poor stability while with the more basic diiron centre in 6 readily forms the stable bridging-hydride complex [(μ-H)Fe₂(CO)₄(μ-dcpm)(μ-pdt)][BF₄] (11) which has been crystallographically characterised.     

Potent anti-platelet constituents from Centaurea iberica

New naturally occurring nitrogenous compounds 1 and 2, along with a new dimeric lignan glucoside 3, have been isolated from the ethyl acetate soluble fraction of Centaurea iberica. Their structures have been elucidated through spectroscopic techniques. All the isolated compounds showed significant platelet aggregation inhibition.     

Solution-based fabrication of a graphene–ZnO nanocomposite

Graphene-based composites represent a new class of materials with potential for many applications. Graphene can be attached to a metal, a semiconductor, or any polymer. In this work, our approach was to attach graphene to a well-known semiconductor, ZnO. We synthesized graphene–ZnO composites by a simple, low-cost, environmentally friendly solvothermal method, carrying out the reaction in different conditions in order to discover the optimum condition, and also to obtain a high-quality product. Our research demonstrated that the optimum temperature to obtain a high-quality product is 180 °C for 20 h. All obtained products were characterized by X-ray diffraction (XRD), scanning electron microscopy, electron dispersion spectrometry, X-ray photoelectron spectrometry, Raman spectroscopy, Fourier transform infrared spectrometry, UV–visible spectrophotometry, and thermogravimetric analysis. The XRD confirmed that the crystal structure of the ZnO in the nanocomposite was wurtzite type. The prepared composite was stable to 800 °C with its 80 % weight.     

Lack of iGb3 and Isoglobo-Series Glycosphingolipids in Pig Organs Used for Xenotransplantation: Implications for Natural Killer T-Cell Biology

α-1,3-Terminated galactose residues on glycoproteins and glycosphingolipids are recognized by natural anti-α-1,3-galactose antibodies in human serum and cause hyperacute rejection in pig-to-human xenotransplantation. Genetic depletion of α-1,3-galactosyl- transferase-1 in pigs abolishes the hyperacute rejection reaction. However, the isoglo- botriosylceramide (iGb3) synthase in pigs may produce additional α-1,3-terminated galactose residues on glycosphingolipids. In both α-1,3-galactosyltranserase-1 knockout mice and pigs, cytotoxic anti-α-1,3-galactose antibodies could be induced; thus, a paradox exists that anti-α-1,3-galactose antibodies are present in animals with functional iGb3 synthases. Furthermore, iGb3 has been found to be an endogenous antigen for natural killer T (NKT) cells, an innate type of lymphocyte that may initiate the adaptive immune responses. It has been reasoned that iGb3 may trigger the activation of NKT cells and cause the rejection of α-1,3-galactosyltransferase-1-deficient organs through the potent stimulatory effects of NKT cells on adaptive immune cells (see ref.^[20]). In this study, we examined the expression of iGb3 and the isoglobo-series glycosphingolipids in pig organs, including the heart, liver, pancreas, and kidney, by ion-trap mass spectrometry, which has a sensitivity of measuring 1% iGb3 among Gb3 isomers, when 5 μg/mL of the total iGb3/Gb3 mixture is present (see ref.^[35]). We did not detect iGb3 or other isoglobo-series glycosphingolipids in any of these organs, although they were readily detected in mouse and human thymus and dendritic cells. The lack of iGb3 and isoglobo-series glycosphingolipids in pig organs indicates that iGb3 is unlikely to be a relevant immune epitope in xenotransplantation.     

A simple dot-blot–Sirius red-based assay for collagen quantification

The assessment of collagen content in tissues is important in biomedical research, since this protein is altered in numerous diseases. Hydroxyproline and Sirius red based assays are the most common methods for collagen quantification. However, these procedures have some pitfalls, such as the requirement of oxygen-free medium or expensive equipment and large sample size or being unsuitable for hydrolyzed collagen, respectively. Our objective was to develop a specific, versatile, and user-friendly quantitative method applicable to small tissue samples and extracts obtained from elastin purification, therefore, suitable for simultaneous quantification of elastin. This method is based on the binding of Sirius red to collagen present in a sample immobilized on a PVDF membrane, as in the dot-blot technique, and quantified by a scanner and image analysis software. Sample loading, Sirius red concentration, temperature and incubation time, type of standard substance, albumin interference, and quantification time are optimized. The method enabled the quantification of (1) intact collagen in several rat tissue homogenates, including small resistance-sized arteries, (2) partially hydrolyzed collagen obtained from NaOH extracts, compatible with elastin purification, and (3) for the detection of differences in collagen content between hypertensive and normotensive rats. We conclude that the developed technique can be widely used since it is versatile (quantifies intact and hydrolyzed collagen), requires small sample volumes, is user-friendly (low-cost, easy to use, minimum toxic materials, and reduced time of test), and is specific (minimal interference with serum albumin).