Polymyxin B-loaded PVP-capped silver nanoparticles: A potent approach against multidrug-resistant bacteria

The rapid emergence of multidrug-resistant (MDR) bacteria poses a critical global health threat, severely limiting the effectiveness of current antibiotics. Polymyxin B (PMB) remains a last-line treatment for MDR Gram-negative infections; however, its clinical use is restricted by nephrotoxicity, neurotoxicity, and the growing prevalence of resistance. This study reports the development of PMB-loaded silver nanoparticles (AgNPs) stabilized with polyvinylpyrrolidone (PVP) as a novel antimicrobial delivery system. The nanoparticles were synthesized via chemical reduction and optimized for PMB loading. The prepared nanoparticles were characterized using UV-vis spectroscopy, dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA). The optimized formulation (PMB-AgNPs-0.5) exhibited an average size of 95.9 ± 0.28 nm, a polydispersity index of 0.202 ± 0.06, encapsulation efficiency of 70.79 ± 2.5%, and a zeta potential of +2.82 mV. In antibacterial assays, PMB-AgNPs-0.5 significantly enhanced inhibition zones compared with free PMB and blank AgNPs: S. aureus (8.1 → 14.5 mm), E. coli (12.8 → 17.1 mm), and P. aeruginosa (12.9 → 17.2 mm). Notably, PMB-resistant S. aureus strains became sensitive, while PMB-sensitive E. coli and P. aeruginosa exhibited further increased susceptibility. Cytocompatibility studies in human dermal fibroblasts confirmed improved safety, with >80% cell viability maintained at bactericidal concentrations, compared with ∼75% for free PMB. These findings highlight PMB-loaded PVP-AgNPs as a promising nanotherapeutic platform with enhanced antibacterial efficacy, reduced toxicity, and significant potential as an effective strategy for combating multidrug-resistant (MDR) bacterial infections.