Chitosan and naringenin-coated silver nanoparticles as a nanoplatform against drug-resistant uropathogens.

Urinary tract infections (UTIs) have now become a serious global public health problem and are difficult to treat due to an increase in resistance to the available antibiotics. Therefore, new therapeutic approaches are urgently required. In this study, we reported the eco-friendly synthesis of naringenin-loaded, chitosan-capped silver nanoparticles (N-C@AgNPs) and evaluated their antibacterial, antioxidant, and anti-inflammatory activities against drug-resistant uropathogens, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. UV–visible spectroscopy, dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) confirmed the formation of stable, spherical nanoparticles. The antimicrobial activity of N-C@AgNPs, determined by the disc diffusion assay, showed zones of inhibition ranging from 8 to 15 mm against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, whereas the untreated control showed negligible inhibition. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were observed in the ranges of 6.25–12.50 µg/mL and 12.50–25 µg/mL, respectively, against these uropathogens. The N-C@AgNPs exhibited concentration-dependent biofilm inhibition and eradication. At 30 µg/mL, the nanoparticles inhibited biofilm formation by 69.82% for K. pneumoniae and 72.55% for P. aeruginosa, while at 100 µg/mL,, the nanoparticles eradicated 80.66% and 74.29% of mature biofilms, respectively. Live/dead staining further confirmed the effective biofilm eradication at a concentration of 100 µg/mL. The N-C@AgNPs also exhibited antioxidant activity (DPPH IC₅₀: 48.87 µg/mL) and were non-cytotoxic to THP-1 cells up to 100 µg/mL compared to control cells. Moreover, N-C@AgNPs significantly suppressed the expression of pro-inflammatory cytokines, including TNF-α, IL-6, IFN-γ, CCL2, and CXCL8, in lipopolysaccharide (LPS)-stimulated THP-1 cells compared to control cells. These findings highlight the therapeutic potential of N-C@AgNPs as a safe and effective alternative for combating infections caused by drug-resistant uropathogens.