Fabrication and Evaluation of Voriconazole Loaded Transethosomal Gel for Enhanced Antifungal and Antileishmanial Activity

Voriconazole (VRC) is a broad-spectrum antifungal agent belonging to BCS class II (biopharmaceutical classification system). Despite many efforts to enhance its solubility, this primary issue still remains challenging for formulation scientists. Transethosomes (TELs) are one of the potential innovative nano-carriers for improving the solubility and permeation of poorly soluble and permeable drugs. We herein report voriconazole-loaded transethosomes (VRCT) fabricated by the cold method and followed by their incorporation into carbopol 940 as a gel. The prepared VRCT were evaluated for % yield, % entrapment efficiency (EE), surface morphology, possible chemical interaction, particle size, zeta potential, and polydispersity index (PDI). The optimized formulation had a particle size of 228.2 nm, a zeta potential of −26.5 mV, and a PDI of 0.45 with enhanced % EE. Rheology, spreadability, extrudability, in vitro release, skin permeation, molecular docking, antifungal, and antileishmanial activity were also assessed for VRCT and VRC loaded transethosomal gel (VTEG). Ex-vivo permeation using rat skin depicted a transdermal flux of 22.8 µg/cm²/h with enhanced efficiency up to 4-fold. A two-fold reduction in inhibitory as well as fungicidal concentration was observed against various fungal strains by VRCT and VTEG besides similar results against L-donovani. The development of transethosomal formulation can serve as an efficient drug delivery system through a topical route with enhanced efficacy and better patient compliance.     

Biogenic Synthesis of Silver Nanoparticles Using Catharanthus roseus and Its Cytotoxicity Effect on Vero Cell Lines

Background: Type 2 diabetes mellitus (DM2) is a chronic and sometimes fatal condition which affects people all over the world. Nanotherapeutics have shown tremendous potential to combat chronic diseases—including DM2—as they enhance the overall impact of drugs on biological systems. Greenly synthesized silver nanoparticles (AgNPs) from Catharanthus roseus methanolic extract (C. AgNPs) were examined primarily for their cytotoxic and antidiabetic effects. Methods: Characterization of C. AgNPs was performed by UV–vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and atomic force microscopy (AFM). The C. AgNPs were trialed on Vero cell line and afterwards on an animal model (rats). Results: The C. AgNPs showed standard structural and functional characterization as revealed by FTIR and XRD analyses. The zetapotential analysis indicated stability while EDX analysis confirmed the formation of composite capping with Ag metal. The cytotoxic effect (IC50) of C. AgNPs on Vero cell lines was found to be 568 g/mL. The animal model analyses further revealed a significant difference in water intake, food intake, body weight, urine volume, and urine sugar of tested rats after treatment with aqueous extract of C. AgNPs. Moreover, five groups of rats including control and diabetic groups (NC1, PC2, DG1, DG2, and DG3) were investigated for their blood glucose and glycemic control analysis. Conclusions: The C. AgNPs exhibited positive potential on the Vero cell line as well as on experimental rats. The lipid profile in all the diabetic groups (DG1-3) were significantly increased compared with both of the control groups (p < 0.05). The present study revealed the significance of C. AgNPs in nanotherapeutics.     

LC-MS/MS-Based Metabolomic Profiling of Constituents from Glochidion velutinum and Its Activity against Cancer Cell Lines

This study aimed to establish the phytochemical profile of Glochidion velutinum and its cytotoxic activity against prostate cancer (PC-3) and breast cancer (MCF-7) cell lines. The phytochemical composition of G. velutinum leaf extract and its fractions was established with the help of total phenolic and flavonoid contents and LC-MS/MS-based metabolomics analysis. The crude methanolic extract and its fractions were studied for pharmacological activity against PC-3 and MCF-7 cell lines using the MTT assay. The total phenolic content of the crude extract and its fractions ranged from 44 to 859 µg GAE/mg of sample whereas total flavonoid contents ranged from 20 to 315 µg QE/mg of sample. A total of forty-eight compounds were tentatively dereplicated in the extract and its fractions. These phytochemicals included benzoic acid derivatives, flavans, flavones, O-methylated flavonoids, flavonoid O- and C-glycosides, pyranocoumarins, hydrolysable tannins, carbohydrate conjugates, fatty acids, coumarin glycosides, monoterpenoids, diterpenoids, and terpene glycosides. The crude extract (IC₅₀ = 89 µg/mL), the chloroform fraction (IC₅₀ = 27 µg/mL), and the water fraction (IC₅₀ = 36 µg/mL) were found to be active against the PC-3 cell line. However, the crude extract (IC₅₀ = 431 µg/mL), the chloroform fraction (IC₅₀ = 222 µg/mL), and the ethyl acetate fraction (IC₅₀ = 226 µg/mL) have shown prominent activity against breast cancer cells. Moreover, G. velutinum extract and its fractions presented negligible toxicity to normal macrophages at the maximum tested dose (600 µg/mL). Among the compounds identified through LC-MS/MS-based metabolomics analysis, epigallocatechin gallate, ellagic acid, isovitexin, and rutin were reported to have anticancer activity against both prostate and breast cancer cell lines and might be responsible for the cytotoxic activities of G. velutinum extract and its bioactive fractions.     

Nanoparticles positioning effect on properties of (PS-PANI/NiNPs) nanocomposite films

This work presents the effect of driven nickel nanoparticles (NiNPs) towards the surface of (PS-PANI)/NiNPs nanocomposite upon the application of a uniform magnetic field. The purpose is to obtain distinguishable optoelectronic and electrical properties. This process increases the surface roughness and its reactivity, and enables the tuning of the optical and electrical properties. Based on the results from X-ray photoelectron and Fourier-transform infrared spectroscopies, the magnetically-driven NiNPs to the surface are oxidized, forming NiONPs and NiOHNPs. This oxidation effect transforms the surface from a hydrophilic to a hydrophobic state. In addition, the optical bandgap energy decreases from 4.04 to 3.77 eV, and the electrical conductivity increases from 12.77 μS/cm to 57.80 μS/cm and 77.52 μS/cm, for 50 and 100 mT magnetic fields, respectively, which is attributed to the well-dispersed magnetic nanoparticles in the PS-PANI polymer matrix, resulting in a high homogeneous nanocomposite film.     

Linear Symmetries of Scattering Amplitudes

If we define, roughly, linear symmetries as those symmetries which lead to linear relationships among scattering amplitudes, we are then faced with the question whether we already know all possible types of linear symmetries or whether there are new types of symmetries which we can yet discover. We argue that for an important class of these symmetries there can be no new types of symmetries, except for one which we call scaling symmetry. We also attempt to point out all types of symmetries which other classes have. In analyzing the above question we are led to a simple and consistent formalism for describing linear symmetries which takes linearity as the starting point for dealing with these symmetries. In this approach all linear symmetries are formally treated on an equal footing. General results on linear symmetries are derived: These symmetries are then classified into three main classes, and an effort is made to discover the characteristic properties of the individual classes.