Insights into the recent advancements of cephalosporins and their nanoformulations in antibacterial applications

Cephalosporins are extensively utilized β-lactam antibiotics for the treatment of respiratory, skin, soft tissue, urinary tract, and systemic bacterial infections. However, their extensive and inappropriate use has augmented antimicrobial resistance, reducing their clinical effectiveness. This review recapitulates the physicochemical properties, antibacterial mechanisms, and the challenges of the development of resistance to cephalosporins. Bacteria can develop resistance via pathways, including production of β-lactamase enzymes, mutations in penicillin-binding proteins, efflux pumps, and reduced aqueous-filled protein channels in the outer membrane, which restrict cephalosporin entry. The literature survey was conducted in PubMed, Google Scholar, and ScienceDirect using relevant terms. The current review elucidates the role of nanoparticles in overcoming antibiotic resistance to cephalosporins. Lipid-based, polymeric, inorganic, and hybrid nanocarriers can help avoid antibiotic resistance by disrupting bacterial membrane defenses; limiting drug resistance mechanisms, such as blocking efflux pumps and inactivating β-lactamases; reducing biofilm formation; providing targeted drug delivery; and enhancing solubility. The nanoformulations of first- to fourth-generation cephalosporins demonstrate improved pharmacokinetic performance and therapeutic outcomes against multidrug-resistant pathogens, whereas studies on fifth-generation cephalosporins remain limited. The primary challenges that hinder clinical translation of cephalosporin-based nanoformulations include β-lactam instability, formulation scalability, regulatory approval, low drug loading, and long-term safety.