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.

Keywords: antifouling; catheter associated urinary tract infections; liquid-infused; nitric oxide; silicone Foley urinary catheter.

Figure 1.

(A) RSNO donor, SNAP, molecular structure. (B) NO release and disulfide bond formation mechanism from RSNOs.

Figure 2.

Swelling characteristics over 72-h period and deswelling characteristics over the remaining 14-day period of the urinary catheter in silicone oil for the LI-UC and LINORel-UC (n = 3). Error bars are excluded since they are on the order of data point size.

Figure 3.

Leaching characteristics of SNAP from NORel-UC and LINORel-UC during first the 24 h period of soaking in PBS at 37 °C and the 24 h leaching characteristics of SNAP from LINORel-UC during the 72 h silicone oil swelling period under ambient conditions using UV–vis spectroscopy (n = 3). Samples were protected from light throughout the study. Data represent mean ± SEM.

Figure 4.

(A) Average nitric oxide release measurements from NORel-UC and LINORel-UC over a 60 day period (n = 3). NO release measured from catheter samples submerged in PBS at 37 °C using a Sievers Chemiluminescence Nitric Oxide Analyzer. Data represent mean ± SEM. (B) Cumulative release of NO from NORel-UC and LINORel-UC over a 60 day period under physiological conditions resulting from the leaching and degradation of the SNAP molecule.

Figure 5.

S. aureus and P. aeruginosa bacteria adhesion per cm² for control commercial urinary catheter, NORel-UC, LI-UC, and LINORel-UC over 24 h period (n = 3). Data represent mean ± SD.

Figure 6.

Bacteria adhesion for control commercial urinary catheter, NORel-UC, LI-UC, and LINORel-UC after 7 days of exposure to S. aureus in a drip flow bioreactor study (n = 3). Data represent mean ± SD.