Reduction in thrombosis and bacterial adhesion with 7 day implantation of S-nitroso-N-acetylpenicillamine (SNAP)-doped Elast-eon E2As catheters in sheep

Abstract

Thrombosis and infection are two common problems associated with blood-contacting medical devices such as catheters. Nitric oxide (NO) is known to be a potent antimicrobial agent as well as an inhibitor of platelet activation and adhesion. Healthy endothelial cells that line the inner walls of all blood vessels exhibit a NO flux of 0.5~4×10 −10 mol cm −2 min −1 that helps prevent thrombosis. Materials with a NO flux that is equivalent to this level are expected to exhibit similar anti-thrombotic properties. In this study, NO-releasing catheters were fabricated by incorporating S-nitroso-N-acetylpenicillamine (SNAP) in the Elast-eon E2As polymer. The SNAP/E2As catheters release physiological levels of NO for up to 20 d, as measured by chemiluminescence. Furthermore, SNAP is stable in the E2As polymer, retaining 89% of the initial SNAP after ethylene oxide (EO) sterilization. The SNAP/E2As and E2As control catheters were implanted in sheep veins for 7 d to examine the effect on thrombosis and bacterial adhesion. The SNAP/E2As catheters reduced the thrombus area when compared to the control (1.56 ± 0.76 and 5.06 ± 1.44 cm 2 , respectively). A 90% reduction in bacterial adhesion was also observed for the SNAP/E2As catheters as compared to the controls. The results suggest that the SNAP/E2As polymer has the potential to improve the hemocompatibility and bactericidal activity of intravascular catheters, as well as other blood-contacting medical devices (e.g., vascular grafts, extracorporeal circuits).

Characterization of an S-nitroso-N-acetylpenicillamine–based nitric oxide releasing polymer from a translational perspective

“…[11, 23] One of the prime objectives in developing NOrel materials is to control as well as prolong the NO-release from these devices. Increasing the lifetime of these materials is generally done through increasing the amount of NO donor that is incorporated in the host material.…”

“…[23] Longer terms studies have been reported recently of SNAP-E2As catheters, and showed reduce bacterial adhesion and thrombus formation for 7 days in sheep. [11] As evident from the previous studies described above, SNAP-doped E2As possesses great potential for biomedical applications. While NO-releasing polymers have been shown to give excellent results in research settings, antibacterial activity and prevention of thrombus formation are not the only properties to consider when moving towards clinically relevant polymers.…”

“…[1-7] It has been shown that NO is the primary regulator in inhibiting platelet activation and adhesion [8-11], and is naturally released from vasculature at an estimated rate of 0.5 – 4 × 10 −10 mol min −1 cm −2 . [12] In addition, NO has broad-spectrum antibacterial properties, and is effective against both gram-positive and gram-negative bacteria.…”

“…Among various NO donors that have been investigated, synthetic S -nitrosothiols (RSNOs) have been studied extensively. [10, 11, 18, 21-29] Release of NO from these materials can occur through thermal decomposition, catalysis (using metals ions such as Cu + ) [30], or by exposure to light [29, 31, 32], resulting in disulfide species (RSSR) formation. S -nitroso-acetylpenicillamine (SNAP) is a synthetic RSNO which has shown to exhibit significant antimicrobial and antithrombotic effects in a various medical grade polymers.…”

“…S -nitroso-acetylpenicillamine (SNAP) is a synthetic RSNO which has shown to exhibit significant antimicrobial and antithrombotic effects in a various medical grade polymers. [11, 14, 23, 33] The delivery of NO from SNAP leads to a molecule of NO and the backbone of the donor, N -acetylpenicillamine (NAP). N -acetylpenicillamine has been used to treat cystinuria at dosages of 2-4 g/day, where only 1 transient episode of facial swelling due to hypersensitivity was seen out of 155 treatment days.…”