Long-Term Stability of Glucose Responsive Dextran Methacrylate-Concanavalin A Methacrylamide Gels as Part of an Implantable Artificial Pancreas

Abstract

A closed loop implantable insulin delivery device that delivers insulin to the peritoneum in an automated fashion linked to changing glucose levels has been developed and previously tested in diabetic rats and pigs. The device delivers insulin via a glucose-sensitive gel that comprises of photopolymerized acrylic derivatives of dextran and concanavalin A and acts as both a sensor and controller of the amount of insulin released. In this work the long-term stability of these acrylic polymerized gels and also dextran and concanavalin A mixtures has been shown at 20°C and 37°C by rheological characterization when stored with and without 0.1% w/w glucose. Acrylic gels were found to have a stable complex viscosity for over 730 days at these temperatures indicating that over time they do not undergo degradation. Mixtures and polymerized gels were also dialyzed in the presence of chymotrypsin, which is present in the peritoneum (device implant site) to assess gel integrity across a range of pore size dialysis membranes. Polymerized acrylic gels contained in dialysis membranes of 50 kDa were found to be resistant to degradation over a long time (>500 days). These results show that these gels would be ideal candidates as part of an implantable insulin delivery device.