Development of S-Nitroso-N-Acetylpenicillamine Impregnated Medical Grade Polyvinyl Chloride for Antimicrobial Medical Device Interfaces.

Abstract

In the clinical setting, polyvinyl chloride (PVC) accounts for 25% of all polymers used in medical device applications. However, medical devices fabricated with plasticized PVC, such as endotracheal tubes, extracorporeal circuits (ECCs), or intravenous catheters, can lead to thrombosis and infection complications. Mortality associated with hospital associated infections (HAIs) exceed 100,000 deaths each year. One method to overcome these challenges is to develop bioactive polymers with nitric oxide (NO) release. Nitric oxide exhibits many physiological roles including antibacterial, antithrombic, and anti-inflammatory activity. In this study, plasticized Tygon PVC tubing was impregnated with a NO donor molecule, S-nitroso-N-acetylpenicillamine (SNAP), via a simple solvent-swelling-impregnation method, where polymer samples were submerged in a SNAP impregnation solvent (methanol, acetone, plasticizer), rinsed, and dried. An additional topcoat of a biocompatible CarboSil 2080A (CB) was applied to reduce SNAP leaching. The SNAP-PVC-CB was characterized for NO release using chemiluminescence, leaching with UV-vis spectroscopy, surface characterization with scanning electron microscopy, tensile strength analysis, stability during storage and sterilization, and antimicrobial properties in vitro. The SNAP-PVC-CB exhibited an NO flux of 4.29 ± 0.80 × 10-10 mol cm-2 min-1 over the initial 24 h under physiological conditions and continued to release physiological levels of NO for up to 14 d (incubated in PBS buffer at 37 °C). The addition of the CB topcoat reduced the total SNAP leaching by 60% during incubation. Mechanical properties and surface topography remained similar to the original PVC after SNAP impregnation and application of the CB topcoat. After ethylene oxide sterilization and 1 month of storage, the SNAP-PVC-CB demonstrated excellent SNAP stability (ca. 90% SNAP remaining). In a 24 h antibacterial assay, SNAP-PVC reduced viable bacteria colonization (ca. 1 log reduction) of S.aureus and E.coli compared to PVC controls. This simple method for SNAP impregnation of medical grade plasticized PVC holds great potential for improving the biocompatibility of postfabricated, plasticized PVC medical devices.