Coumarin-triazole hybridized as therapeutic-based niosomes for advanced drug release of Cefixime against multi-drug resistance Salmonella enterica

Bacterial resistance to conventional antibiotics has become a massive problem for healthcare systems. This could result in serious consequences for treating bacterial infections, including treatment failure. In turn, drug resistance has promoted the development of more effective antibacterial agents. Niosomes are considered efficient agents for the enhancement of the antibacterial activity of antibiotics. Herein, Coumarin-triazole hybrid (CAT) niosomes were developed and evaluated against extensively drug-resistant Salmonella enterica (XDR S. enterica). The Cefixime-loaded CAT niosomal vesicle average particle size was 342 ± 3 nm, with a zeta potential −28 ± 2.0 mV. CAT vesicles showed a prominent drug entrapment efficiency of 74% ± 3%. A blood hemolytic assay revealed no hemolysis occurred. CAT vesicle exhibited a reduced cytotoxic effect against NIH/3T3 normal mouse fibroblast cells, at the maximum concentration of 1000 μg/mL. However, the MIC₅₀ empty and Cefixime loaded CAT niosomal vesicles against XDR S. enterica was observed at 250 and 125 μgmL⁻¹, respectively, indicating that Cefixime lowered the MIC₅₀ by two-fold. Topographical atomic force microscopy (AFM) images revealed that exposure to Cefixime-loaded CAT niosomes efficiently damaged the bacterial cell membrane of XDR S. enterica, resulting in leaking and scattering.