Combating Gram-negative infections: The role of antimicrobial peptides and nanotechnology in overcoming antibiotic resistance

Abstract

Gram-negative bacterial infections represent a critical global health threat due to rising antibiotic resistance, posing substantial clinical and economic burdens. The structural complexity of Gram-negative bacteria—including efflux pumps, enzymatic degradation mechanisms, genetic mutations, and altered membrane permeability, significantly complicates treatment with conventional antibiotics. Antimicrobial peptides (AMPs) offer great antimicrobial activity, rapid bactericidal effects, multiple mechanisms of action, and immune-modulatory properties. However, their clinical application is limited by enzymatic degradation, potential cytotoxicity, and high production costs. To address these limitations, advanced nanotechnology-based platforms, including lipid-based nanoparticles, polymeric nanoparticles, and inorganic nanoparticles, are being explored as AMP delivery vehicles. These nanocarriers enhance peptide stability, bioavailability, targeted delivery, and therapeutic efficacy while reducing systemic toxicity. This review synthesizes recent advancements in AMPs and nanotechnology-based delivery systems, highlighting their combined potential to effectively combat multidrug-resistant Gram-negative pathogens.