Fatty Acid‐Based Nanoparticles: The Synergistic Antibacterial Potential of Cefixime Against Drug‐Resistant Bacteria

ABSTRACT

Antimicrobial resistance (AMR), driven largely by indiscriminate antibiotic use, urgently needs attention. Free fatty acids (FFAs) are conserved components of unicellular eukaryotes, yet their use as nanoparticle‐based antibiotic‐sensitizing agents remains unexplored. We formulated myristic acid (C14) and lauric acid (C12) into oleic acid‐stabilized nanostructured lipid carriers (NLCs, MOD and LOD) by hot‐melt micro‐emulsification and loaded them with cefixime (MOD‐C and LOD‐C). Optimized NLCs measured 133–144 nm with zeta potentials of −19 to −25.8 mV. SEM confirmed spherical morphology, and entrapment efficiency exceeded 80%. DSC and FTIR confirmed successful encapsulation and component compatibility, and drug‐loaded particles released cefixime more slowly than a free‐drug suspension. Against five non‐resistant reference strains, E. coli , P. aeruginosa , K. pneumoniae , S. aureus , and B. subtilis , all formulations, blank and drug‐loaded, were active, with cefixime‐loaded NLCs (MIC 16.068–17.046 µg/mL) slightly better than free cefixime (MIC 20 µg/mL). Blank NLCs alone partially restored activity, with MOD against resistant E. coli only and LOD against resistant E. coli and P. aeruginosa , but neither inhibited MRSA. Loading the same carriers with cefixime, however, restored full antibacterial activity against all three resistant strains. These findings show that FFA‐based NLCs not only deliver cefixime but also resensitize otherwise cefixime‐resistant bacteria.