Liquid-Infused Nitric-Oxide-Releasing Silicone Foley Urinary Catheters for Prevention of Catheter-Associated Urinary Tract Infections

Abstract

Urinary catheterization is one of the most common medical procedures that makes a patient susceptible to infection due to biofilm formation on the urinary catheter. Catheter associated urinary tract infections (CAUTIs) are responsible for over 1 million cases in the United States alone and cost the healthcare industry more than $350 million every year. This work presents a liquid-infused nitric-oxide-releasing (LINORel) urinary catheter fabricated by incorporating the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) and silicone oil into commercial silicone Foley catheters through a two-stage swelling process. This synergistic combination improves NO-releasing materials by providing minimal SNAP leaching and a more controlled release of NO while incorporating the nonfouling characteristics of liquid-infused materials. The LINORel urinary catheter was successful in sustaining a controlled NO release over a 60 day period under physiological conditions with minimal SNAP leaching during the initial 24 h period, 0.49 ± 0.0061%. The LINORel-UC proved successful in reducing bacterial adhesion and biofilm formation for Gram positive Staphylococcus aureus (98.49 ± 2.06%) over a 7 day period in a drip flow bioreactor environment. Overall, this study presents a desirable combination that incorporates the antifouling advantages of liquid-infused materials with the active release of a bactericidal agent, an uncharted territory in aiding to prevent the risk of CAUTIs.

Antibacterial efficacy from NO-releasing MOF–polymer films

“…Indeed, insufficient delivery is often a factor that results in low, ineffective and/or slow antimicrobial efficacy from many systems and warrants the combination of NO with other agents such as silver nanoparticles. 15,16,41,42 Our previous studies have confirmed that concentrations of NO released from MOF powders can be effective against a wide range of bacteria, including antibiotic resistant strains, such as MRSA. 43 However, to date, our reported studies have focused on the function of and efficacy from MOF powders.…”

“…Several approaches are being studied to achieve NO release from catheters including direct impregnation of NO 13 and attachment and/or incorporation of NO-binding compounds (such as NONOates and S-nitrosothiols) to the polymer employed to manufacture the catheter. [14][15][16] We are interested in developing metal organic frameworks (MOFs) as NO releasing agents. MOFs are crystalline microporous materials comprised of metal ion or cluster nodes connected by organic ligands.…”

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

“…As a result, researchers at the turn of the century began to use antiviral NO-based therapeutics through three different strategies: 1) compounds that modulate endogenous production of NO, 2) gaseous NO (gNO) inhalation, and 3) direct NO donor compounds. More recently, NO-releasing and catalytic NO-generating surfaces have been developed for blood-contacting and other indwelling medical devices to combat bacterial infection and prevent blood thrombus formation that are often associated with urinary/vascular catheters, mechanical ventilators, and ex vivo blood circulation in dialysis and extracorporeal membrane oxygenation (ECMO) [12] , [13] , [14] .…”

S‐Nitroso‐N‐acetylpenicillamine impregnated endotracheal tubes for prevention of ventilator‐associated pneumonia

“…Common methods of incorporating NO donors such as SNAP include swelling the polymer with a solvent swelling solution (Brisbois, Major, Goudie, Bartlett et al, 2016; Colletta et al, 2015), immobilization of the donor onto the polymer itself (Frost & Meyerhoff, 2005; Reynolds et al, 2006), or physically blending the NO donor with the polymer in solution (Brisbois et al, 2015; Brisbois, Handa, Major, Bartlett, & Meyerhoff, 2013). The efficacy of NO‐releasing materials as a bactericidal agent has been demonstrated in numerous in vitro studies using materials incorporated with SNAP against common bacteria (Brisbois, Major, Goudie, Bartlett et al, 2016; Brisbois, Major, Goudie, Meyerhoff et al, 2016; Goudie, Pant, & Handa, 2017; Homeyer, Goudie, Singha, & Handa, 2019; Singha, Pant, Goudie, Workman, & Handa, 2017). Specifically, Feit et al (2019) have shown that the incorporation of a NO‐releasing donor into medical grade PVC, a common material used to produce ETTs, reduced viable bacteria colonization of Staphylococcus aureus and Escherichia coli over a 24‐hr period.…”

“…Common methods of incorporating NO donors such as SNAP include swelling the polymer with a solvent swelling solution Colletta et al, 2015), immobilization of the donor onto the polymer itself (Frost & Meyerhoff, 2005;Reynolds et al, 2006), or physically blending the NO donor with the polymer in solution (Brisbois et al, 2015;Brisbois, Handa, Major, Bartlett, & Meyerhoff, 2013). The efficacy of NO-releasing materials as a bactericidal agent has been demonstrated in numerous in vitro studies using materials incorporated with SNAP against common bacteria Homeyer, Goudie, Singha, & Handa, 2019;Singha, Pant, Goudie, Workman, & Handa, 2017). Specifically, Feit et al (2019)…”