Plant-derived hydrolates are aqueous co-products of hydrodistillation that remain underexplored despite their potential as sustainable ingredients for topical formulation design. This study comparatively evaluated two topical semisolid platforms for hydrolate valorization: a thermoresponsive gel containing Anacardium occidentale L. hydrolate and an emulgel containing Pectis brevipedunculata hydrolate associated with babassu oil. Both systems were based on Pluronic F127 and Carbopol 974P and were characterized by physical stability assessment, Fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, and semiquantitative antimicrobial screening against Escherichia coli, Staphylococcus aureus, and Candida albicans. Incorporation of the whole hydrolate-containing aqueous fractions into the complete formulations was associated with formulation-dependent changes in matrix organization and resazurin-based metabolic activity scores. The A. occidentale hydrolate-loaded gel showed a visually observed temperature-associated change in physical form, spectroscopic evidence compatible with non-covalent hydrolate–polymer interactions, reduced crystallinity, compact lamellar morphology, and a lower resazurin score at the highest tested formulation condition. The P. brevipedunculata hydrolate-loaded emulgel preserved the structural identity of the polymer–lipid matrix and showed a descriptive one-point lower score against C. albicans at the lower tested formulation condition. Because hydrolate chemical profiles, droplet-size analysis, zeta potential, rheology, pH, release/permeation, and cytocompatibility assays were not performed, the findings should be interpreted as preliminary formulation-level evidence rather than direct mechanistic, safety, or efficacy proof. Overall, this study supports further investigation of plant-derived hydrolates as value-added aqueous co-products in sustainable topical semisolid platforms. Hydrolates were valorized as functional aqueous phases in topical semisolid platforms. A thermoresponsive gel and a babassu oil emulgel were compared on the same polymer base. FTIR, DSC, and SEM indicated formulation-dependent changes in matrix organization. Resazurin screening showed descriptive differences against bacteria and C. albicans. Findings are preliminary formulation-level evidence, not mechanistic or efficacy proof.
To develop and validate an LC-MS/MS method for the quantification of Tenalisib, a dual phosphoinositide 3-kinase δ/γ inhibitor in mouse plasma. Protein precipitation technique was employed to extract Tenalisib from mouse plasma, with tolbutamide selected as the internal standard (IS). A clean chromatographic separation of Tenalisib and the IS was achieved on a Zorbax SB Phenyl (50 × 4.6 mm, 3.5 μm) column using an isocratic mobile phase (0.1
KRAS mutations, mainly G12C, hyperactivate oncogenic signaling in breast cancer, promoting tumor proliferation, metastasis, and resistance to standard treatments through dysregulated downstream effectors like PI3K/AKT/mTOR. Direct targeting of KRAS remains difficult due to its undruggable GTPase pocket, highlighting the need for innovative computer-aided drug design (CADD) and biophysics strategies. In this study, various approaches were employed to identify potential KRAS inhibitors. Molecular docking analysis with PyRx 0.8 predicted binding free energies of -10.3 kcal/mol, -10.3 kcal/mol, and − 10.1 kcal/mol for Top-1, Top-2, and Top-3, respectively. The top-ranked docked compounds were further examined through molecular dynamics simulations to assess the stability of the complexes. A 100-ns simulation confirmed their stability, showing minimal deviations throughout the entire period. Additionally, favorable MM-PBSA net binding energies validated these lead compounds for targeting PI3Kα-mutant breast cancer. SwissADME analysis and physicochemical properties, including Lipinski’s rule of five, confirmed that these compounds possess drug-like characteristics. RMSD analysis revealed an initial increase during the equilibration phase, followed by stable convergence during the simulation. Notably, the Top-1 ligand-protein complex exhibited the lowest RMSD values, around 4.29 Å with minor fluctuations, indicating a highly stable binding conformation. Furthermore, RMSF analysis demonstrated that the Top-1 ligand remained the most biologically relevant and dynamically stable over the 100-ns simulation, suggesting its potential for sustained inhibitory activity in breast cancer treatment. Next, the compactness and relaxation of the ligand-protein complexes were investigated via radius of gyration (Rg) and B-factor analysis. All the selected top-three ligand-protein docked complexes showed comparatively stable Rg values during simulation time, signifying the constant structural integrity of the complexes. Furthermore, the overall Rg plots of each docked complex analysis specify that ligand binding does not significantly destabilize the overall protein structure. MM-GBSA binding free energy calculation predicted − 107.3 kcal/mol, -104.32 kcal/mol, and − 96.67 kcal/mol net free binding energy for Top-1. Top-2 and Top-3, respectively. MM-PBSA analysis predicted − 105.85 kcal/mol, -102.22 kcal/mol, and − 95.04 kcal/mol net binding for Top-1. Top-2 and Top-3, respectively. Overall, bioinformatics, biophysics screening, and binding free energy calculation findings showed that the selected Top-1 ligand is the most biologically relevant and stable in the dynamic, highlighting its potential as a drug candidate for the treatment of breast cancer.
The present investigation was carried out to synthesize monometallic copper (CuONPs), zinc (ZnONPs) and bimetallic copper oxide-zinc oxide nanoparticles (CuO-ZnO NPs) via a green route using Allium cepa (onion) and Zingiber officinale (ginger) extracts. The prepared NPs were analyzed using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy and ultraviolet–visible (UV–Vis) spectroscopy. Following characterization, the NPs were assessed for their antimicrobial, antioxidant and anticancer activities. The anticancer activity was evaluated against the MCF-7 breast cancer and HepG2 hepatic cell lines. Hemolytic activity was evaluated to assess cytotoxicity. The bimetallic CuO–ZnO NPs exhibited superior biological performance compared to their monometallic counterparts. The CuO–ZnO NPs demonstrated enhanced anticancer activity relative to CuONPs and ZnONPs. In vitro cytotoxicity against hepatocellular carcinoma (HepG2) cells assessed by the MTT assay showed a dose-dependent reduction in cell viability. Notably, CuO–ZnO NPs showed the higher inhibition (52.64
Metformin hydrochloride is a first line oral antidiabetic medication, and it is known to cause weight loss as a side effect. The exact mechanism responsible for this side effect is unknown. In addition, the administration of a conventional immediate-release tablet of metformin is associated with gastrointestinal side effects. Enteric coating can modify metformin release in vitro, and this pH-dependent dissolution could establish an intestinal localization, which may aid in the GLP-1-mediated mechanism in vivo. To evaluate enteric-coated metformin tablets and compare post-treatment metabolic outcomes with immediate-release metformin, liraglutide, and dietary controls in male Sprague-Dawley rats. Seven nominal 70-mg cores containing 40 mg metformin hydrochloride were formulated and screened. F7 was selected and coated with Kollicoat MAE 30 DP (FEC1) or Eudragit L100 (FEC2). Sixty rats were assigned to five groups (12/group). After five months of high-fat feeding, treatment continued for eight weeks; the normal-diet control remained on standard feed. Metformin was administered at 40 mg/rat/day; FEC2 was used in vivo. Only post-treatment outcomes were measured. FEC1 and FEC2 released 8 ± 2
