Zinc‐oxide nanoparticles act catalytically and synergistically with nitric oxide donors to enhance antimicrobial efficacy

Abstract

The development of infection‐resistant materials is of substantial importance as seen with an increase in antibiotic resistance. In this project, the nitric oxide (NO)‐releasing polymer has an added topcoat of zinc oxide nanoparticle (ZnO‐NP) to improve NO‐release and match the endogenous NO flux (0.5–4 × 10−10 mol cm−2 min−1). The ZnO‐NP is incorporated to act as a catalyst and provide the additional benefit of acting synergistically with NO as an antimicrobial agent. The ZnO‐NP topcoat is applied on a polycarbonate‐based polyurethane (CarboSil) that contains blended NO donor, S‐nitroso‐N‐acetylpenicillamine (SNAP). This sample, SNAP‐ZnO, continuously sustained NO release above 0.5 × 10−10 mol cm−2 min−1 for 14 days while samples containing only SNAP dropped below physiological levels within 24 h. The ZnO‐NP topcoat improved NO release and reduced the amount of SNAP leached by 55% over a 7‐day period. ICP‐MS data observed negligible Zn ion release into the environment, suggesting longevity of the catalyst within the material. Compared to samples with no NO‐release, the SNAP‐ZnO films had a 99.03% killing efficacy against Staphylococcus aureus and 87.62% killing efficacy against Pseudomonas aeruginosa. A cell cytotoxicity study using mouse fibroblast 3T3 cells also noted no significant difference in viability between the controls and the SNAP‐ZnO material, indicating no toxicity toward mammalian cells. The studies indicate that the synergy of combining a metal ion catalyst with a NO‐releasing polymer significantly improved NO‐release kinetics and antimicrobial activity for device coating applications. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 00A: 000–000, 2019.

Prevention of medical device infections via multi‐action nitric oxide and chlorhexidine diacetate releasing medical grade silicone biointerfaces

“…Previous studies have shown polymeric medical devices with NO‐releasing capacity for the use of endotracheal tubes, insulin cannula, catheters, extracorporeal circulation, and so forth 17,49,52 . Results obtained in this study align with previously published articles that emphasize the compatibility of SNAP‐loaded polymers for biomedical applications 59,66 . Cell compatibility studies confirmed >70% cell survival rate with all samples (Figure 8).…”

Nitric oxide and viral infection: Recent developments in antiviral therapies and platforms

“…3 d) as well as from covalently attached NO donors through various biodegradation mechanisms [125 , 127] . Additionally, NO-releasing scaffolds and nanoparticles have been designed to target organs and tissues to deliver payloads following stimuli-response to differences in oxidation environment or the presence of catalytic metal ions [127] , [128] , [129] , [130] , [131] . Through rational design approaches, NO-releasing formulations could be developed to target specific viral disease states.…”

Nitric Oxide-Releasing Polymeric Materials for Antimicrobial Applications: A Review

“…Therefore, increasing the release amount of NO is completely necessary. Researchers have designed catalytic release systems by combining SNAP with catalysts such as platinum nanoparticles [115], copper nanoparticles (Cu-NPs) [116], Cu 1.6 S nanoparticle [117], zinc oxide nanoparticles [118], ebselen [119], or selenium [120], to achieve a large amount release of NO. Handa et al top-coated 1, 3, and 5 wt % of Cu-NPs to SNAP doped Carbosil films to fabricate Cu-SNAP films.…”