Quercetin solid dispersion as promising reducing agent for synthesis of ecofriendly chitosan-silver nanoparticles: A prospective nanoconjugate of meropenem against carbapenem -resistant gram-negative bacilli

Carbapenems are antibiotics that have been employed to treat infections caused by Gram-negative multidrug resistant bacteria. This investigation focused on the development of nanoconjugate green synthesized silver-chitosan nanoparticle to improve the antibacterial activity and minimize bacterial resistance to meropenem. Silver nanoparticles were developed by green synthesis method which utilized highly solubilized quercetin solid dispersion as reducing agent. The synthesized silver nanoparticles formulation underwent evaluation using different approaches. Meropenem nano-conjugate was fabricated and characterized for particle size, conjugation efficiency and in vitro release. The effectiveness of the meropenem nanoconjugate against carbapenem-resistant gram-negative bacterial isolates was investigated. Gene expression of carbapenemase producing isolates treated with nanoconjugate was monitored. The prepared meropenem nanoconjugate exhibited nanosized range (221.7±4.5 nm) and displayed conjugation efficiency of 85%. The IC50 of meropenem conjugate on the human foreskin fibroblast (HFF)-1 normal cell line was found 114.45±3.97 µg/ml indicating a negligible cytotoxic effect. Meropenem nanoconjugate was found to have the lowest minimum inhibitory concentration (MIC) when compared to free meropenem. Additionally, treatment of carbapenem-resistant bacterial cells with meropenem nanoconjugate resulted in the down regulation of carbapenem resistant gene expression. Therefore, the nano-conjugate of meropenem chitosan - silver nanoparticles presents a promising nano-platform for enhancing antibacterial efficacy and downregulating carbapenem resistance-associated genes.