Nitric Oxide Generating Polymeric Coatings for Subcutaneous Glucose Sensors

摘要

Heretofore efforts to develop implantable sensors for real-time clinical monitoring of glucose subcutaneously (SQ) in diabetic patients have been hindered by the unreliable analytical results owing largely to biocompatibility problems induced by sensor implantation (e.g. inflammatory/foreign body response). The goal of this research program is to explore and optimize the chemistries required to fabricate implantable amperometric glucose sensors with outer polymeric coatings that slowly generate low levels of nitric oxide (NO). Release of NO has been shown to enhance the biocompatibility of the implanted sensors by decreasing the inflammatory response. The focus of this research has been to develop new polymeric coatings (biomedical hydrogels and polyurethanes) that possess immobilized copper ion sites or organoselenium and organotellurium species that will serve as catalytic sites for in situ conversion of endogenous nitrosothiol species (RSNO) to NO thereby providing a sustained local generation of NO species at the surface of the implanted sensors. Preliminary biocompatibility experiments suggest that RSNO levels within the SQ fluid of rats may be sufficient to generate enough local NO to reduce the inflammatory response at the implant site. New needle type sensors are being developed to determine the levels of RSNOs in the SQ region. Finally functional needle type SO glucose sensors have been prepared with both NO release and NO generation coatings. These sensors provide the basis of assessing if NO generationireleasing chemistries are compatible with glucose sensing chemistries.