Enhanced antibacterial efficacy of nitric oxide releasing thermoplastic polyurethanes with antifouling hydrophilic topcoats

Singha, Priyadarshini; Pant, Jitendra; Goudie, Marcus J.; Workman, Christina D.; Handa, Hitesh

doi:10.1039/c6bm00948d

Cited by 64 publications

(92 citation statements)

References 82 publications

(59 reference statements)

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“…E2As‐SNAP catheters which can inhibit bacteria up to 2 logs in the presence of blood protein without causing cytotoxicity to provide an initial proof of concept for their potential biocompatibility. The results from this study overlap with other studies which show NO releasing surfaces to be highly effective in their antibacterial potential without any cytotoxic response, hemolysis, and platelet activation …”

Section: Resultssupporting

confidence: 79%

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Nitric oxide releasing vascular catheters for eradicating bacterial infection

et al. 2017

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The interaction of blood proteins with an implant surface is not only a fundamental phenomenon but is also key to several important medical complications. Plasma proteins binding on the surface of intravascular catheters can promote bacterial adhesion leading to the risk of local and systemic complications such as catheter-related blood infections (CRBIs). The incidences of CRBIs in the United States amount to more than 250,000 cases/year with an attributable mortality of up to 35% and an annual healthcare expenditure of $2.3 billion approximately. This demands the development of truly nonthrombogenic and antimicrobial catheters. In the present study, catheters were fabricated by incorporating a nitric oxide (NO) donor molecule, S-nitroso-N-acetyl-penicillamine (SNAP) in a hydrophobic medical grade polymer, Elasteon-E2As. NO offers antithrombotic and antibacterial attributes without promoting drug resistance and cytotoxicity. E2As-SNAP catheters were first coated with fibrinogen, a blood plasma protein plays a key role in clot formation and eventual bacterial adhesion to the implant surface. The suitability of the catheters for biomedical applications was tested in vitro for contact angle, NO release kinetics, inhibition of bacteria, and absence of cytotoxicity toward mammalian cells. The highly hydrophobic catheters released NO in the physiological range that inhibited >99% bacterial viability on fibrinogen-coated catheters in a 24 h study. No toxic response of E2As-SNAP catheters leachate was observed using a standard cytotoxicity assay with mouse fibroblast cells. Overall, the results showed that the E2As-SNAP catheters can inhibit viable bacteria even in the presence of blood proteins without causing a cytotoxic response. The fundamentals of this study are applicable to other blood-contacting medical devices as well. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2849-2857, 2018.

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Section: Resultssupporting

confidence: 79%

“…The results from this study overlap with other studies which show NO releasing surfaces to be highly effective in their antibacterial potential without any cytotoxic response, hemolysis, and platelet activation. 16,19,40,78…”

Section: Inhibition Of Gram-positive and Gram-negative Bacterial Growmentioning

confidence: 99%

Nitric oxide releasing vascular catheters for eradicating bacterial infection

et al. 2017

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“…This problem can be addressed by the application of NO. The small molecular size of NO allows it to diffuse through the bacterial biofilm and kill the bacterial cells which are otherwise resistant to bactericidal agents [53, 54]. In other words, the gradually released NO extended the life of BPAM by lowering the concentration of surrounding bacteria near the surface.…”

Section: Resultsmentioning

confidence: 99%

“…The NO released within the sinus cavities and macrophages functions as a natural antimicrobial agent to non-specifically combat pathogen invasion in mammals including humans [37]. Over the past two decades, NO-based therapies have emerged as a potential bactericidal agent to kill even the most prevalent pathogens causing hospital-acquired infection such as methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa , and other bacteria including Escherichia coli, Acinetobacter baumanii, Listeria monocytogenes , and Enterococcus faecalis [29, 46–54]. The nonspecific innate immune response of NO results from lipid peroxidation and tyrosine nitration in the cell wall, nitrosation of amines and thiols in the extracellular matrix, and DNA cleavage in the cellular matrix [55].…”

Section: Introductionmentioning

confidence: 99%

A multi-defense strategy: Enhancing bactericidal activity of a medical grade polymer with a nitric oxide donor and surface-immobilized quaternary ammonium compound

et al. 2017

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Although the use of biomedical devices in hospital-based care is inevitable, unfortunately, it is also one of the leading causes of the nosocomial infections, and thus demands development of novel antimicrobial materials for medical device fabrication. In the current study, a multi-defense mechanism against Gram-positive and Gram-negative bacteria is demonstrated by combining a NO releasing agent with a quaternary ammonium antimicrobial that can be covalently grafted to medical devices. Antibacterial polymeric com posites were fabricated by incorporating a nitric oxide (NO) donor, S-nitroso-N-acetyl-penicillamine (SNAP) in CarboSil® polymer and top coated with surface immobilized benzophenone based quaternary ammonium antimicrobial (BPAM) small molecule. The results suggest that SNAP and BPAM have a different degree of toxicity towards Gram-positive and Gram-negative bacteria, and the SNAP-BPAM combination is effective in reducing both types of adhered viable bacteria equally well. SNAP-BPAM combinations reduced the adhered viable Pseudomonas aeruginosa by 99.0% and Staphylococcus aureus by 99.98% as compared to the control CarboSil films. Agar diffusion tests demonstrate that the diffusive nature of NO kills bacteria beyond the direct point of contact which the non-leaching BPAM cannot achieve alone. This is important for potential application in biofilm eradication. The live-dead bacteria staining shows that the SNAP-BPAM combination has more attached dead bacteria (than live) as compared to the controls. The SNAP-BPAM films have increased hydrophilicity and higher NO flux as compared to the SNAP films useful for preventing blood protein and bacterial adhesion. Overall the combination of SNAP and BPAM imparts different attributes to the polymeric composite that can be used in the fabrication of antimicrobial surfaces for various medical device applications.

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“…CarboSil is a polycarbonate‐based polyurethane that contains a silicone segment and is marketed by DSM. It has been used previously by our and other groups and has been found to have stable NO‐releasing properties when incorporated with SNAP . (Exact properties are not public knowledge but all details are available on the company's website.)…”

Section: Methodsmentioning

confidence: 99%

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

Singha

Workman

Pant

et al. 2019

J Biomedical Materials Res

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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.

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Enhanced antibacterial efficacy of nitric oxide releasing thermoplastic polyurethanes with antifouling hydrophilic topcoats

Cited by 64 publications

References 82 publications

Nitric oxide releasing vascular catheters for eradicating bacterial infection

Nitric oxide releasing vascular catheters for eradicating bacterial infection

A multi-defense strategy: Enhancing bactericidal activity of a medical grade polymer with a nitric oxide donor and surface-immobilized quaternary ammonium compound

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

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