Nano-antimicrobial peptides (Nano-AMPs) to combat resistant gram-negative bacteria.

The emergence of antimicrobial resistance (AMR) poses a critical threat to public health worldwide, making conventional antibiotics ineffective against multidrug-resistant (MDR) pathogens. This literature review examines the potential therapeutic applications of nano-antimicrobial peptides (Nano-AMPs), with a focus on multidrug-resistant pathogens prioritized by the World Health Organisation (WHO). Antimicrobial peptides (AMPs) are essential components of the innate immune system with broad-spectrum bactericidal and immunomodulatory properties, and have emerged as promising alternatives to conventional antibiotics because of their unique mechanisms of action (e.g., membrane disruption, pore formation, and immunomodulation). Currently, the clinical translation of AMPs is hindered by several challenges, including enzymatic and non-enzymatic degradation, poor bioavailability, and biocompatibility issues, as well as local and systemic adverse events. To address these concerns, recent advancements in nanocarrier delivery systems offer novel solutions, enabling selected and targeted drug delivery, enhanced bioavailability, and controlled and sustained AMP release. Lipid-based nanocarriers (e.g., liposomes), polymeric and other nanocarrier systems improve peptide solubility and limit off-target events, while inorganic carriers like gold, silver, and silica nanoparticles facilitate functionalization and synergism to combat MDR Gram-negative infections. Despite promising findings, challenges such as production, long-term efficacy and safety, and regulatory approval persist. Therefore, interdisciplinary efforts, such as advanced machine learning methods alongside conventional pharmacological approaches, may be needed to optimize nanocarrier designs and validate clinical efficacy and safety in preclinical and clinical trials. This review critically analyses the latest evidence on different nanocarriers and their synergistic effects, highlighting their transformative potential to combat AMR, thereby offering insights to develop next-generation antibiotics, particularly against Gram-negative pathogens.