Nitric Oxide-Releasing Lock Solution for the Prevention of Catheter-Related Infection and Thrombosis
Morgan Ashcraft, Megan Douglass, Mark Garren, Arnab Mondal, Lori Estes Bright, Yi Wu, Hitesh Handa
Abstract
Although frequently used, venous catheters are often associated with serious complications such as infection and thrombosis. Lock solution therapies are clinically used to deter these issues but generally address only infection or thrombosis with limited success. Here, we report the development of a dual-functional lock therapy using nitric oxide (NO) donor molecule, S-nitrosoglutathione (GSNO). NO is a potent, broad-spectrum antimicrobial agent that also temporarily inhibits platelet activation, preventing thrombosis. Furthermore, NO has antibiofilm actions, an ability that traditional antibiotic lock solutions lack, thus limiting their efficacy. In this work, different concentrations of GSNO were characterized via NO analysis to determine a range of NO-releasing lock solution (NOreLS) concentrations to investigate and to demonstrate prolonged potential efficacy. Tested against clinically used vancomycin and gentamicin lock solutions, GSNO-based NOreLS repeatedly outperformed in models of different stages of catheter infections. NOreLS also prevented clot formation when exposed to whole blood, showing increased efficacy compared to a heparin lock solution. Moreover, NOreLS was demonstrated to be biocompatible via hemolysis and cytotoxicity assays. NOreLS has excellent potential for safely and effectively preventing infection and thrombosis related to catheter usage.