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Tunable nitric oxide release from S-nitroso-N-acetylpenicillamine via catalytic copper nanoparticles for biomedical applications.

Research paper by Jitendra J Pant, Marcus James MJ Goudie, Sean P SP Hopkins, Elizabeth J EJ Brisbois, Hitesh H Handa

Indexed on: 15 Apr '17Published on: 15 Apr '17Published in: ACS Applied Materials & Interfaces



Abstract

The quest for novel therapies to prevent bacterial infections and blood clots (thrombosis) is of utmost importance in biomedical research due to exponential growth in cases of thrombosis, 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 biological functions. The physiological effect of NO is dose dependent, that necessitates the need of 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 levels of catalytic copper nanoparticles (Cu-NPs). The addition of Cu-NPs increased the NO release as well as the overall antimicrobial activity via its oligodynamic effect. The 10 wt% SNAP composites (without Cu-NPs coats) showed an NO flux of 1.32 ± 0.6 x10-10 mol min-1 cm-2, while Cu-NPs incorporated SNAP films exhibited a flux of 4.48 ± 0.5 x10-10, 4.84 ± 0.3 x10-10, and 11.7 ± 3.6 x10-10 mol min-1 cm-2 with 1 wt%, 3 wt%, 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 the corresponding controls. Copper leachates from the SNAP films were detected using ICP-MS technique and were found to be significantly lower than the recommended safety limit by the FDA. The cell viability test performed on mouse fibroblast 3T3 cells provides a supportive evidence for the biocompatibility of the material in vitro.