Gold nanoparticles (Au) have attracted considerable attention in the field of biomedicine in recent years. The present work was designed to investigate gold nanoparticles obtained using a soil-associated actinomycetes, Streptomyces sp. ASM19. This microorganism was isolated and identified using DNA sequencing. The chemical profile of the Streptomyces sp. ASM19 extract was analyzed using LC-HRES-MS. Streptomyces sp. ASM19 extract was utilized to synthesize actinomycetes-based gold nanoparticles (Ac-AuNPs), which were analyzed using ultraviolet-visible (UV-vis) spectrophotometry, Fourier transform infrared (FTIR) spectroscopy, and atomic force microscopy (AFM). In addition, the antibacterial, and anti-biofilm, as well as, the anti-proliferative properties of Ac-AuNPs against seven cancer lines were investigated. LC-HRES-MS analysis traced a total of 111 peaks, 14 of them are key peaks belonging to the chemical classes, alkaloids, steroids, and polyketides. Analysis of the synthesized Ac-AuNPs revealed that they exhibited a wine-red color and a plasmon band appeared at 540 nm, confirming the formation of the Ac-AuNPs. Further, FTIR confirmed various functional groups present in Ac-AuNPs. The crude extract of Streptomyces sp. ASM19 demonstrated consistent antibacterial activity in contrast to Ac-AuNPs. The anti-proliferative properties of Ac-AuNPs demonstrated encouraging anticancer properties against SCC9 and SCC25 cell lines with IC₅₀ values of 3.77 and 1.56 μg mL⁻¹. Furthermore, Ac-AuNPs had total apoptotic percentages of 26.37% (SCC9) and 32.08% (SCC25), which are around 25 times higher than the control (0.95%). Additionally, it caused a notable G2/M phase cell-cycle arrest. On the other hand, molecular docking study carried out for the annotated compounds; tomaymycin (8) and nocapyrone P (5), showed considerable binding affinities compared to the co-crystallized inhibitor (fisetin) against the cyclin-dependent kinase 6 active site. Overall, the present study could be useful for nano drug delivery and may be applied for clinical studies in the future.

Background: Itraconazole (ITZ) is an antiangiogenic agent recognized as a potent suppressor of endothelial cell growth that suppresses angiogenesis. Nevertheless, its exploitation is significantly restricted by its low bioavailability and systematic side effects. The objective of this study was to utilize glycerosomes (GLY), glycerol-developed vesicles, as innovative nanovesicles for successful ITZ pulmonary drug delivery. Methods: The glycerosomes were functionalized with hyaluronic acid (HA-GLY) to potentiate the anticancer efficacy of ITZ and extend its local bio-fate. ITZ-HA-GLY were fabricated using soybean phosphatidylcholine, tween 80, HA, and sonication time via a thin-film hydration approach according to a 24 full factorial design. The impact of formulation parameters on ITZ-HA-GLY physicochemical properties, as well as the optimal formulation option, was evaluated using Design-Expert^®. Sulphorhodamine-B (SRB) colorimetric cytotoxicity assay of the optimized ITZ-HA-GLY versus ITZ suspension was explored in the human A549 cell line. The in vivo pharmacokinetics and bio-distribution examined subsequent to intratracheal administrations of ITZ suspension, and ITZ-HA-GLY were scrutinized in rats. Results: The optimized ITZ-HA-GLY unveiled vesicles of size 210.23 ± 6.43 nm, zeta potential of 41.06 ± 2.62 mV, and entrapment efficiency of 73.65 ± 1.76%. Additionally, ITZ-HA-GLY manifested a far lower IC50 of 13.03 ± 0.2 µg/mL on the A549 cell line than that of ITZ suspension (28.14 ± 1.6 µg/mL). Additionally, the biodistribution analysis revealed a higher concentration of ITZ-HA-GLY within the lung tissues by 3.64-fold as compared to ITZ suspension. Furthermore, the mean resistance time of ITZ-HA-GLY declined more slowly with 14 h as compared to ITZ suspension, confirming the accumulation of ITZ inside the lungs and their promising usage as a target for the treatment of lung disease. Conclusions: These data indicate that the improved ITZ-HA-GLY demonstrates significant promise and represents an exciting prospect in intratracheal delivery systems for lung cancer treatment, meriting further investigation.

The emergence of multidrug-resistant bacterial infections is a major global public health concern. Human health is in danger from microorganisms that have developed resistance to currently used drugs. Honey is well known for its significant activity against antibiotic-resistant bacteria. In this study, the antibacterial properties of honey from various botanical sources in Saudi Arabia against seven significant nosocomial and foodborne pathogens were investigated. The physicochemical properties of four Saudi honey samples—aloe honey (HO1) (Aloe vera L.), anise honey (HO2) (Pimpinella anisum L.), moringa honey (HO4) (Moringa oleifera Lam.), and acacia honey (HO5) (Acacia sp.)—were examined. In addition, they were screened for antibacterial activity against ESKAPE pathogens (Enterobacter faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella Typhimurium, Escherichia coli, and Enterobacter sp.) and anti-biofilm activity against four pathogenic bacteria strains: S. aureus, P. aeruginosa, S. typhimurium, and E. coli. ¹H NMR profiling and multivariate analysis (PCA and PLS-DA) were performed. Aloe honey (HO1) was the most distinct sample based on MVDA and its antibacterial activity, and it exhibited anti-biofilm activity against most biofilm-forming microorganisms. Its metabolic profile was deduced using LC-MS, and the resulting annotated compounds were docked against several β-lactamase enzyme classes. The results reveal the potential of honey-derived compounds to inhibit β-lactamases due to the presence of gallic acid hexoside and rosmarinic acid, suggesting their potential as competitive inhibitors. Our findings suggest that further honey antibacterial compounds could offer a novel approach to overcoming antibiotic resistance by targeting and inhibiting β-lactamase enzymes.

The main aim of this study is to develop pH-dependent nanocomposite and to investigate in-vitro drug release at different pH, antibacterial efficacy, and the mechanical properties. The commercial flowable composite (FC) were modified with the formulated CHX-MSN nanoparticles at different concentrations (1%, 5% and 10%) and examined at two time points (baseline and aged for 3 months in artificial saliva) for its antimicrobial, drug release, and mechanical behavior. The antibiofilm efficacy and biofilm adhesion of the specimens were measured with crystal violet (CV) assay, MTT assay, and Confocal laser microscopy (CSLM). The mechanical properties were evaluated by surface microhardness and flexural strength. Modified FC exhibited pH-dependent drug release kinetics and maintained for up to 30 days. At a pH of 5.5, 10% CHX-MSN doped FC showed the highest CHX release profile. The antibiofilm efficacy was significantly increased in all modified groups (p<0.05) compare to control. After 3 months of ageing in artificial saliva, modified group with 5% CHX-MSN showed significant increase in surface microhardness properties (p<0.01). The experimental groups (1% and 5% CHX-MSN) displayed higher flexural strength (FS) value compared to the control at baseline. The pH dependent release of CHX was observed in modified FC. Considering both mechanical and antibacterial performance, the experimental group modified with 5% CHX-MSN might be optimal for achieving clinical needs and enhancing longevity of the material.

Background/Objectives: Propolis is a resinous natural product rich in phenolic acids and flavonoids, recognized in ethnopharmacology for its antioxidant and anti-inflammatory properties. This study aimed to identify the most bioactive Saudi propolis extract using a bioassay-guided strategy and investigate its chemical profile and mechanistic anti-inflammatory potential. Methods: Four propolis extracts (P1–P4) collected from different regions of Saudi Arabia were evaluated for their antioxidant (DPPH and ABTS) and anti-inflammatory (COX-1 and COX-2) activities. The most active extract was profiled using liquid chromatography–mass spectrometry (LC–MS), followed by molecular docking and molecular dynamics simulations. Results: Among all samples, P3 demonstrated the strongest antioxidant activity, with IC₅₀ values of 25.84 ± 0.96 µg/mL (DPPH) and 32.30 ± 1.20 µg/mL (ABTS), comparable to ascorbic acid (27.45 ± 1.42 and 21.22 ± 0.79, respectively). P3 also exhibited potent and selective COX-2 inhibition with an IC₅₀ of 6.19 ± 0.21 µg/mL (relative to celecoxib, IC₅₀ 0.681 ± 0.02 as positive control). LC–MS analysis identified 26 secondary metabolites. Computational studies ranked kaempferol as forming the most conformationally stable COX-2 complex among the ligands examined, including the reference inhibitor, on the basis of molecular dynamics descriptors of pose persistence and conformational confinement. Conclusions: Saudi propolis P3 is a potent source of bioactive compounds with strong antioxidant and selective COX-2 inhibitory activity. These findings highlight its anti-inflammatory potential and suggest its value as a natural lead for developing safer therapeutics targeting inflammation-related chronic diseases.