Increasing the Lifetime of Insulin Cannula with Antifouling and Nitric Oxide Releasing Properties.

Abstract

Many Type 1 diabetes patients utilize insulin pumps, which rely on a small subcutaneous insulin infusion cannula. However, insulin cannulas still suffer from infection and inflammation, which impacts the wear time of the insulin cannula, reduces the efficiency of insulin infusion, and requires frequent rotation of the insulin infusion site. Infection and inflammation of continuous insulin infusion pump therapy are growing issues and are estimated to cost billions of dollars globally each year. This study aims to develop a potent antibacterial and antifouling insulin cannula with a synergistic effect of bioinspired polymers, integrating antifouling slippery, liquid-infused porous surface technology with an active nitric oxide (NO) releasing polymer. The cannulas were developed by impregnating the NO donor molecule S-nitroso-N-acetylpenicillamine (SNAP) and silicone oil (Si) in commercial medical-grade silicone rubber (SR) tubing (SR-SNAP-Si) via a solvent-impregnation process. The efficiency of the SR-SNAP-Si to reduce protein adsorption and provide antibacterial properties against Staphylococcus aureus and Staphylococcus epidermidis were studied using in vitro bioassays. The SR-SNAP-Si cannula released NO for more than 14 d at physiological levels and were stable during storage for 30 d at room temperature. Scanning electron microscopy images revealed no observable changes to the material surface after the solvent impregnation process. The infusion of silicone oil significantly reduced the protein adsorption on the cannula by 66.40%, and the NO release reduced the viable bacterial cell adhesion of S. epidermidis and S. aureus after 24 h by 94.89% and 99.77%, respectively, as compared to SR controls. This insulin cannula provided continuous NO release and an antifouling interface for more than 14 d and exhibited significant reduction in protein and bacterial adhesion. This method of developing dual-function nitric oxide releasing and antifouling surface for subcutaneous insulin infusion cannulas holds great potential to reduce infection and inflammation associated with insulin pump delivery systems.