A novel nanotherapeutic approach: Dual action of green-synthesized silver nanoparticles from Clerodendrum serratum against MDR-ESKAPE pathogens with wound healing potential

The rapid emergence of multidrug-resistant (MDR) ESKAPE pathogens in healthcare settings, particularly chronic wound infections presents a critical challenge. Moreover, with antibiotic resistance reaching alarming levels and conventional treatments failing against biofilm-associated infections, there is an urgent need to develop novel and effective therapeutic strategies. In this study, silver nanoparticles (AgNPs) synthesized via a green method using Clerodendrum serratum leaf extract, along with their polyethylene glycol-coated derivative (PEG-AgNPs), were evaluated for their antibacterial and wound-healing potential. PEG-AgNPs demonstrated superior antibacterial efficacy, with significantly lower minimum inhibitory concentration (MIC) values (0.3906–12.5 μg/mL) compared to AgNPs (3.125–25 μg/mL). Time-kill studies further confirmed that PEG-AgNPs exhibited enhanced bactericidal properties. Mechanistic investigations revealed that their antibacterial activity resulted from bacterial cell membrane rupture, leading to cytoplasmic content leakage, as confirmed by FACS analysis. Furthermore, biofilm formation by these pathogens was evaluated, and the nanoparticles demonstrated remarkable anti-biofilm potency, particularly against Acinetobacter baumannii and Pseudomonas aeruginosa. The LC-MS analysis of C. serratum leaf extract revealed bioactive phytoconstituents, which were subjected to molecular docking studies against biofilm-forming factors in P. aeruginosa and A. baumannii confirming strong binding interactions. Additionally, the prepared nanoparticle-based gel formulations significantly enhanced in vivo wound healing in both uninfected and infected (A. baumannii and P. aeruginosa) wounds, highlighting their potential as dual-action therapeutic agents for inhibiting MDR pathogens and simultaneously promoting tissue regeneration. Therefore, these findings suggest that green synthesized nanoparticles, particularly PEG-AgNPs hold promise as novel interventions for combating MDR-ESKAPE infected wounds.