Chitosan-coated niosomal meropenem with enhanced antibacterial and antibiofilm activity against carbapenem-resistant Klebsiella pneumoniae from wastewater

(CRKP) poses a major therapeutic challenge due to antimicrobial resistance and biofilm formation. This study developed chitosan-coated meropenem-loaded niosomes (Nio-MRP@CS) and evaluated their physicochemical properties and antibacterial, antibiofilm, and gene-modulating activities against wastewater-derived CRKP isolates. Niosomes were prepared by thin-film hydration using Span 60, Tween 60, and cholesterol, with meropenem (MRP) incorporated during hydration, followed by chitosan coating. The optimised formulation (F2) showed an entrapment efficiency (EE%) of 74.16 ± 2.12%, particle size of 131.5 ± 3.3 nm, and polydispersity index (PDI) of 0.131 ± 0.004. Nio-MRP@CS released 42.55% of MRP over 72 h, compared with 49.5% from Nio-MRP and 98-100% from free MRP by 24 h. MIC values decreased from 50-100 to 1.56-12.5 μg/mL, while biofilm formation was inhibited by 60-70%. Nio-MRP@CS also reduced blaIMP, blaKPC, and fimH expression. These findings support Nio-MRP@CS as an in-vitro delivery platform. Further in-vivo, toxicity, pharmacokinetic, and safety studies are required before clinical translation.