Fabrication, optimization, and characterization of pH-responsive PEGylated nanoniosomes containing gingerol for enhanced treatment of breast cancer.

Multiple potential drug delivery strategies have emerged as a result of recent advances in nanotechnology and nanomedicine. The aim of this research was to prepare an optimized system of PEGylated gingerol-loaded niosomes (Nio-Gin@PEG) as an excellent candidate for the treatment of human breast cancer cells. The preparation procedure was modified by adjusting the drug concentration, lipid content, and Span60/Tween60 ratio, resulting in high encapsulation efficacy (EE%), rapid release rate, and reduced size. The Nio-Gin@PEG exhibited significantly improved storage stability compared to the gingerol-loaded niosomes formulation (Nio-Gin), with minimal changes in EE%, release profile, and size during storage. Furthermore, Nio-Gin@PEG demonstrated pH-dependent release behavior, with delayed drug diffusion at physiological pH and significant drug diffusion under acidic conditions (pH = 5.4), making it a promising option for cancer treatment. Cytotoxicity tests indicated that Nio-Gin@PEG possessed excellent biocompatibility with human fibroblast cells while exerting a remarkable inhibitory effect on MCF-7 and SKBR3 breast cancer cells, attributed to the presence of gingerol and the PEGylated structure in the preparation. Nio-Gin@PEG also exhibited the ability to modulate the expression of target genes. We observed statistically significant down-regulation of the expression of BCL2, MMP2, MMP9, HER2, CCND1, CCNE1, BCL2, CDK4, and VEGF genes, along with up-regulation of the expression of BAX, CASP9, CASP3, and P21 genes. Flow cytometry results revealed that Nio-Gin@PEG could induce a higher rate of apoptosis in both cancerous cells compared to gingerol and Nio-Gin, owing to the optimal encapsulation and efficient drug release from the formulation, as confirmed by cell cycle tests. ROS generation demonstrated the superior antioxidant effect of Nio-Gin@PEG compared to other prepared formulations. The results of this study emphasize the potential of formulating highly biocompatible niosomes in the future of nanomedicine, enabling more precise and effective treatment of cancers.

Ecofriendly Biomolecule-Capped Bifidobacterium bifidum-Manufactured Silver Nanoparticles and Efflux Pump Genes Expression Alteration in Klebsiella pneumoniae.

Background: Klebsiella pneumoniae is currently considered as an immediate threat to human health due to its various multidrug efflux pumps. Microbially synthesized silver nanoparticles (AgNPs) are an attractive and eco-friendly approach to prevent antibiotic resistance in bacteria. In the present study, we compared the inhibitory effect of both commercial and green AgNPs by Bifidobacterium bifidum on OxqAB efflux pump genes in ciprofloxacin-resistant strains of K. pneumoniae. Materials and Methods: AgNPs were characterized by ultraviolet-visible spectrophotometer, Fourier transform infrared spectroscopy, X-ray diffraction, zeta potential, transmission electron microscopy, and scanning electron microscopy. Antibiogram was used to identify resistant isolates and the effect of the biosynthesized AgNPs against OxqAB efflux pump strains was assessed by the minimum inhibitory concentration (MIC) method. The expression levels of oxqAB genes were evaluated using real-time polymerase chain reaction (PCR) followed by exposure to subMICs of the AgNPs. Results: PCR results showed that 25 strains had OxqAB efflux pump and the MIC method indicated that AgNPs had an inhibitory effect on all resistant strains with OxqAB efflux pump. The efficacy of the synthetic nanoparticles was assessed by comparing the antiefflux pump activity with commercial AgNPs. In ciprofloxacin-resistant isolates, the oxqAB genes expression levels reduced in the subMIC of both AgNPs, whereas biosynthesized AgNPs had greater bactericidal effects compared with the commercial AgNPs. Conclusions: Efflux pumps could be an attractive target for our biosynthesized AgNPs. The oxqAB genes expression levels reduced in subMIC of both AgNPs, whereas biosynthesized AgNPs had greater bactericidal effects than the commercial AgNPs.