Improved Hemocompatibility of Multilumen Catheters via Nitric Oxide (NO) Release from S-Nitroso-N-acetylpenicillamine (SNAP) Composite Filled Lumen

Abstract

Blood-contacting devices, such as intravascular catheters, suffer from challenges related to thrombus formation and infection. Nitric oxide (NO) is an endogenous antiplatelet and antimicrobial agent. Exogenous release of NO from various polymer matrices has been shown to reduce thrombosis and infection of/on implantable medical devices. However, the clinical applications of such materials have been hindered due to factors such as NO donor leaching and thermal instability. In this study, a novel approach is demonstrated in which one lumen of commercial dual lumen catheters is dedicated to the NO release chemistry, allowing the other lumen to be available for clinical vascular access. A composite consisting of poly(ethylene glycol) (PEG) and S-nitroso-N-acetylpenicillamine (SNAP) is used to fill the NO-releasing lumen of commercial 7 French silicone catheters. Physiological levels of NO are released from the SNAP-PEG catheters for up to 14 d, as measured by chemiluminescence NO analyzer (in PBS buffer at 37 °C). PEG facilitates the NO release from SNAP within the lumen by increasing the water absorption and slowly dissolving the solid SNAP-PEG composite. In a CDC biofilm bioreactor, the SNAP-PEG catheters are found to reduce > 97% bacterial adhesion as compared to the PEG controls for single bacterial species including E. coli and S. aureus. SNAP-PEG and PEG control catheters were implanted in rabbit veins for 7 h (single lumen) and 11 d (dual lumen) to evaluate their hemocompatibility properties. Significant reductions in thrombus formation on the SNAP-PEG vs. PEG controls were observed, with ca. 85% reduction for 7 h single lumen catheters and ca. 55% reduction for 11 d dual lumen catheters.

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

“…The incorporation of SNAP in medical grade polymers have been shown to be hemocompatible and possesses stability during long-term storage at room temperature and physiological conditions [63, 72, 73]. …”

“…Another report has also shown that hydrophobic polymers with SNAP have extended NO-release at physiological levels (up to 20 days) [70]. Furthermore, the incorporation of SNAP in medical grade polymers are not only hemocompatible and biocompatible but also stable during long-term storage (6 months) at room temperature [63, 72, 73]. …”

“…Out of various biomedical devices that are frequently used in clinical practices, intravenous infusion devices, and urinary catheters represent a major source of nosocomial septicemia [1, 2]. For instance, the incidences of catheter-related bloodstream infections in the United States are approximately 80,000 cases/year in intensive care units alone and up to 250,000 cases/year in total with an attributable mortality of up to 35% [3].…”

A Versatile Surface Bioengineering Strategy Based on Mussel-Inspired and Bioclickable Peptide Mimic

“…Accordingly, we designed a DBCO-capped NO-generating compound for surface engineering. As is well studied in previous work, the transition metal ion Cu(II) has excellent glutathione peroxidase- (GPx-) like activity [ 47 , 48 ], which can catalytically generate NO from both endogenous and synthetic S-nitrosothiols (RSNOs) by decomposing them in the presence of reduced glutathione (GSH). In order to immobilize Cu ions, a cyclen DOTA (1,4,7,10-tetraazacyclododecane- N , N ′, N ″ , N ‴ -tetraacetic acid) was conjugated with a DBCO group ( Figure 4(a) and Figure S4 ) [ 49 ].…”

Nitric Oxide-Producing Cardiovascular Stent Coatings for Prevention of Thrombosis and Restenosis

“…To extend the NO release time, Hopkins et al designed a highly stable NO-releasing coating by covalently attaching SNAP with poly(dimethylsiloxane) (PDMS) (Hopkins et al, 2018 ). Previous studies demonstrated that SNAP-based polymers have exhibited significant leaching of SNAP, which will result in non-localized NO release (Brisbois et al, 2016 ). Through tethering to PDMS, SNAP leaching into surrounding environment was prevented and allowed for lengthened potency.…”