Nitric oxide (NO) is involved in physiological processes, including vasodilatation, wound healing and antibacterial activities. As NO is a free radical, designing drugs to generate therapeutic amounts of NO in controlled spatial and time manners is still a challenge. In this study, the NO donor S-nitrosoglutathione (GSNO) was incorporated into the thermoresponsive Pluronic F-127 (PL)-chitosan (CS) hydrogel, with an easy and economically feasible methodology. CS is a polysaccharide with known antimicrobial properties. Scanning electron microscopy, rheology and differential scanning calorimetry techniques were used for hydrogel characterization. The results demonstrated that the hydrogel has a smooth surface, thermoresponsive behavior and good mechanical stability. The kinetics of NO release and GSNO diffusion from GSNO-containing PL/CS hydrogel demonstrated a sustained NO/GSNO release, in concentrations suitable for biomedical applications. The GSNO-PL/CS hydrogel demonstrated a concentration-dependent toxicity to Vero cells, and antimicrobial activity to Pseudomonas aeruginosa (minimum inhibitory concentration and minimum bactericidal concentration values of 0.5 µg·mL⁻¹ of hydrogel, which corresponds to 1 mmol·L⁻¹ of GSNO). Interestingly, the concentration range in which the NO-releasing hydrogel demonstrated an antibacterial effect was not found to be toxic to the Vero mammalian cell. Thus, the GSNO-PL/CS hydrogel is a suitable biomaterial for topical NO delivery applications.

Background: Nitric oxide (NO) is an antimicrobial and anti-biofilm agent with significant potential for combating biofilm-associated infections and antibiotic resistance. However, owing to its high reactivity due to the possession of a free radical and short half-life (1–5 s), the practical application of NO in clinical settings is challenging. Objectives: This review explores the development of NO-releasing nanoparticles that provide a controlled, targeted delivery system for NO, enhancing its antimicrobial efficacy while minimizing toxicity. The review discusses various NO donors, nanoparticle platforms, and how NO disrupts biofilm formation and eradicates pathogens. Additionally, we examine the highly encouraging and inspiring results of NO-releasing nanoparticles against multidrug-resistant strains and their applications in medical and environmental contexts. This review highlights the promising role of NO-based nanotechnologies in overcoming the challenges posed by increasing antibiotic resistance and biofilm-associated infections. Conclusions: Although NO donors and nanoparticle delivery systems show great potential for antimicrobial and anti-biofilm uses, addressing challenges related to controlled release, toxicity, biofilm penetration, resistance, and clinical application is crucial.