Niosomal delivery of cefoxitin enhances antibacterial and antibiofilm activities against gram-positive and gram-negative bacteria

The rise of antibiotic-resistant bacterial infections is a serious threat to human health. Biofilm formation and limited antibiotic penetration reduce the effectiveness of conventional antibiotics, highlighting the need for more effective drug-delivery strategies. Niosomes, as promising vesicular drug delivery systems, have shown potential to enhance antibiotic efficacy. This study aimed to encapsulate cefoxitin in niosomes and evaluate its antibacterial effect against Gram-negative and Gram-positive bacteria, including Escherichia coli, Acinetobacter baumannii, Staphylococcus aureus, and Listeria monocytogenes. Cefoxitin-loaded niosomes were prepared by thin-layer hydration. Physicochemical properties were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The antibacterial and anti-biofilm activities of free cefoxitin and cefoxitin-loaded niosomes were investigated using microdilution and microtiter plate assays, respectively. Time-kill kinetics were further performed to evaluate bacterial killing kinetics. The findings showed the synthesized niosomes were spherical with a size of 142.3 nm. The release of cefoxitin from niosomes was 62.69% during 72 h, while nearly complete release of free cefoxitin occurred within the same period. Notably, antibacterial investigations revealed that although free cefoxitin showed little effect on Gram-negative bacteria at the concentrations studied, niosomal cefoxitin significantly inhibited their bacterial growth and biofilm formation. Additionally, niosomal cefoxitin enhanced antibacterial and antibiofilm activity compared with free cefoxitin against Gram-positive bacteria. The 72-h time-kill assay showed that niosomal cefoxitin reduced bacterial viability at all time points. The results demonstrate that niosomal delivery enhances the antibacterial activity of cefoxitin and improves its effectiveness against biofilm-forming bacteria.