Tunable Nitric Oxide Release from S-Nitroso-N-acetylpenicillamine via Catalytic Copper Nanoparticles for Biomedical Applications

The quest for novel therapies to prevent bacterial infections and blood clots (thrombosis) is of utmost importance in biomedical research due to the exponential growth in the cases of thrombosis and blood infections and the emergence of multi-drug-resistant strains of bacteria. Endogenous nitric oxide (NO) is a cellular signaling molecule that plays a pivotal role in host immunity against pathogens, prevention of clotting, and regulation of systemic blood pressure, among several other biological functions. The physiological effect of NO is dose dependent, which necessitates the study of its tunable release kinetics, which is the objective of this study. In the present study, polymer composites were fabricated by incorporating S-nitroso-N-acetylpenicillamine (SNAP) in a medical-grade polymer, Carbosil, and top-coated with varying concentrations of catalytic copper nanoparticles (Cu-NPs). The addition of the Cu-NPs increased the NO release, as well as the overall antimicrobial activity-via the oligodynamic effect of Cu. SNAP (10 wt %) composites without Cu-NP coatings showed a NO flux of 1.32 +/- 0.6 x 10-(10) mol min(-1) cm(-2), whereas Cu-NP-incorporated SNAP films exhibited fluxes of 4.48 +/- 0.5 x 10(-10), 4.84 +/- 0.3 x 10(-10), and 11.7 +/- 3.6 x 10(-10) mol min(-1) cm(-2) with 1, 3, and 5 wt % Cu-NPs, respectively. This resulted in a significant reduction (up to 99.8%) in both gram-positive and gram-negative bacteria, with very low platelet adhesion (up to 92% lower) as compared to that of the corresponding controls. Copper leachates from the SNAP films were detected using the inductively coupled plasma-mass spectrometry technique and were found to be significantly lower in concentration than the recommended safety limit by the FDA. The cell viability test performed on mouse fibroblast 3T3 cells provided supportive evidence for the biocompatibility of the material in vitro.