Ciprofloxacin-functionalized silver nanocomposite: a promising strategy against colistin-resistant <b> <i>Pseudomonas aeruginosa</i> </b>

The rapid rise of colistin resistance in Pseudomonas aeruginosa presents a critical challenge, necessitating innovative therapeutic alternatives. In this study, we developed a novel ciprofloxacin-functionalized silver nanocomposite (NC) by modifying phospholipid-PEG (polyethylene glycol)-coated silver nanoparticles to enhance antibacterial efficacy against colistin-resistant P. aeruginosa. The NC was comprehensively characterized by UV-Visible spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, transmission electron microscope, scanning electron microscopy, and EDX, confirming spherical morphology with an average size of 29.74 nm. Biological evaluations revealed potent antibacterial and antibiofilm activity: CFU (colony forming unit) and crystal violet assays demonstrated a 6.9 log₁₀ CFU mL-1 reduction in bacterial colonies and a 31.45% decrease in biofilm formation. Mechanistic studies revealed an elevated production of reactive oxygen species, singlet oxygen, and hydroxyl radicals upon treatment, correlating with a 39.70% decline in bacterial viability in XTT assays. Importantly, methyl thiazolyl tetrazolium cytotoxicity tests against MLE12 cells confirmed the NC's biocompatibility. Efficacy was further validated in an in vivo lung infection model in albino Wistar rats, where histopathological analysis and cytokine profiling confirmed therapeutic potential. Collectively, these findings establish ciprofloxacin-modified silver NCs as a stable, safe, and highly effective strategy for treating multidrug-resistant P. aeruginosa, offering a promising alternative to colistin in combating life-threatening lung infections.