Antimicrobial nitric oxide releasing gelatin nanoparticles to combat drug resistant bacterial and fungal infections

Antimicrobial resistance (AMR) represents a significant global health challenge, contributing to increased mortality rates and substantial economic burdens. The development of new antimicrobial agents with dual antimicrobial and antibiofilm capabilities is crucial to mitigate AMR. Nitric oxide (NO) is a broad-spectrum antimicrobial agent which has shown promise in treating infections due to its multiple antimicrobial mechanisms. However, the high reactivity of NO poses a challenge for effective delivery to infection sites. We investigated the antimicrobial and antibiofilm capabilities, and the shelf life, of NO-releasing gelatin nanoparticles (GNP/NO) against three common hospital-acquired pathogens: <i>Staphylococcus aureus</i>, <i>Escherichia coli</i>, and <i>Candida albicans</i>. The synthesised GNP/NO were found to be cytocompatible and exhibited significant antimicrobial and antibiofilm efficacies against the tested pathogens in both nutrient-rich and nutrient-poor conditions. Furthermore, we found that the antimicrobial capabilities of GNP/NO were maintained for up to 6 months post synthesis, against <i>Staphylococcus aureus</i> (2.4 log), <i>Escherichia coli</i> (1.2 log) and <i>Candida albicans</i> (3 log) under nutrient-poor conditions. Our study demonstrates the use of a novel broad-spectrum antimicrobial with a prolonged shelf life for the treatment of infections. These findings offer an effective alternative to traditional antibiotics which would contribute to mitigating the current global AMR threat resulting from antibiotic overuse.