SBIR-STTR Award

Approximately 24 million adults and children in the United States have 1 Diabetes Mellitus (diabetes) and 1.6 million new cases are diagnosed each year. Type 2 is the most common form of the disease accounting for over 90% of the diabetics worldwide. The remaining 5 to 10% of diabetics are plagued with the more serious Type 1 condition which is most often diagnosed in children, adolescents or young adults and is characterized by the body's inability to produce insulin. Type 1 diabetics living with this disease must frequently monitor their blood glucose levels to prevent deleterious bouts of hyper- or hypoglycemia. The 2010 American Diabetes Association guidelines recommend testing three or more times a day which results in a minimum of 1,095 finger sticks per year. Because of the cost, pain, and inconvenience of needle sticks, many diabetics do not follow the rigorous monitoring schedule necessary for maintaining healthy blood glucose levels. Continuous glucose monitoring systems provide an alternative, real-time method for metabolic control. However, the reliability and resulting clinical utility of continuous glucose monitors is limited due the body's adverse response to subcutaneous implants. Current scientific knowledge regarding nitric oxide's role in reducing inflammation, preventing scar tissue formation, and increasing new blood vessel formation suggests that nitric oxide-releasing surfaces may create an optimal tissue environment to improve the accuracy of continuous glucose monitors. The purpose of this project is to create a nitric oxide-releasing device coating, using Novan's proprietary nitric oxide-releasing nanoparticle technology (Nitricil(tm)), to reduce the foreign body response that occurs upon implantation of subcutaneous glucose sensors. Through this two year, Phase I SBIR the Company aims to: 1) evaluate the foreign body response of Nitricil(tm) coated platinum wires in a rabbit animal model as a function of nitric oxide concentration and release kinetics;2) fabricate four layer enzymatic glucose sensors using the optimized Nitricil(tm) coating from Aim 1 and evaluate sensor response using a <10% loss in sensitivity, response time, and/or linearity as pass/fail criteria;and 3) demonstrate the stability of both the nitric oxide-releasing coating and the enzyme-based sensor function on terminally sterilized sensors over time. Following the completion of Phase I milestones, Novan will explore the scale up of sensor dip-coating procedures, apply the coating to commercially available devices provided by a corporate partner, evaluate the biocompatibility of finished glucose sensors according to ISO-10993 and FDA guidelines, and conduct proof-of-concept testing of the Nitricil(tm)- coated glucose sensor in porcine animal models to establish mean absolute percent deviation from blood glucose levels.

Public Health Relevance:
Approximately 24 million Americans have Diabetes Mellitus (diabetes) at an annual economic cost of nearly $200 billion. Type 1 diabetics living with this disease must frequently monitor their blood glucose levels to prevent deleterious bouts of hyper- or hypoglycemia. Continuous glucose monitoring systems provide a real time method for metabolic control and have made significant strides toward a ""closed-loop"" system. However, the reliability and resulting clinical utility of continuous glucose monitors is limited due the body's poor response to subcutaneous implants. The goal of this Phase I project is to create a nitric oxide-releasing device coating to reduce the foreign body response that occurs upon implantation of subcutaneous glucose sensors and improve the accuracy of these devices.

Thesaurus Terms:
0-11 Years Old;21+ Years Old;Accounting;Acute;Adolescent;Adolescent Youth;Adult;Adult Human;American;Animal Model;Animal Models And Related Studies;Articulation;Blood Glucose;Blood Sugar;Blood Vessels;Body Tissues;Capsules;Cells;Child;Child Human;Child Youth;Children (0-21);Cicatrix;Clinical;Cristobalite;D-Glucose;Development;Devices;Dextrose;Diabetes Mellitus;Diagnosis;Disease;Disorder;Domestic Rabbit;Dose;Electrodes;Endogenous Nitrate Vasodilator;Endothelium-Derived Nitric Oxide;Environment;Enzymes;Family Suidae;Fingers;Foreign Bodies;Glucose;Goals;Guidelines;Humulin R;Hyperglycemia;Hypoglycemia;Immune Response;Implant;Inflammation;Inflammatory;Inflammatory Response;Insulin;Insulin (Ox), 8a-L-Threonine-10a-L-Isoleucine-30b-L-Threonine-;Joints;Kinetics;Knowledge;Loinc Axis 4 System;Laboratories;Life;Measurement;Measures;Membrane;Metabolic Control;Methods;Microelectrodes;Miniaturized Electrodes;Modeling;Monitor;Mononitrogen Monoxide;Needle-Stick Injuries;Needle-Sticks;Needlestick Injuries;Needlesticks;Nitric Oxide;Nitrogen Monoxide;Nitrogen Protoxide;North Carolina;Novolin R;Oryctolagus Cuniculus;Ostamer;Pain;Painful;Pancreas;Pancreatic;Pellethane;Performance;Phase;Pigs;Plague;Platinum;Platinum Black;Polyisocyanates;Polyurethanes;Procedures;Pt Element;Rabbits;Rabbits Mammals;Reaction Time;Regular Insulin;Reliability Of Results;Research;Response Rt;Response Time;Role;Sbir;Sbirs (R43/44);Sand;Scars;Schedule;Series;Silica;Silicon Dioxide;Simulate;Small Business Innovation Research;Small Business Innovation Research Grant;Sterilization;Suidae;Surface;Swine;System;Technology;Testing;Thick;Thickness;Time;Tissues;Tridymite;United States;Universities;Vascularization;Work;Yersinia Pestis Disease;Adult Human (21+);Adult Youth;Adulthood;Base;Biocompatibility;Biomaterial Compatibility;Capsule (Pharmacologic);Children;Clinical Relevance;Clinically Relevant;Commercialization;Cost;Design;Designing;Developmental;Diabetes;Diabetic;Disease/Disorder;Economic Cost;Endothelial Cell Derived Relaxing Factor;Glucose Meter;Glucose Monitor;Glucose Sensor;Host Response;Hyperglycemic;Hypoglycemic;Hypoglycemic Episodes;Immunoresponse;Implant Material;Implantation;Improved;Juvenile;Juvenile Human;Meetings;Membrane Structure;Model Organism;Nano Particle;Nanoparticle;Neovascularization;Pathogen;Porcine;Prevent;Preventing;Psychomotor Reaction Time;Response;Scale Up;Sensor;Social Role;Stability Testing;Subcutaneous;Success;Suid;Type 1 Diabetic;Type I Diabetic;Vascular;Young Adult;Young Adulthood;Youngster

Approximately 24 million adults and children in the United States have 1 Diabetes Mellitus (diabetes) and 1.6 million new cases are diagnosed each year. Type 2 is the most common form of the disease accounting for over 90% of the diabetics worldwide. The remaining 5 to 10% of diabetics are plagued with the more serious Type 1 condition which is most often diagnosed in children, adolescents or young adults and is characterized by the body's inability to produce insulin. Type 1 diabetics living with this disease must frequently monitor their blood glucose levels to prevent deleterious bouts of hyper- or hypoglycemia. The 2010 American Diabetes Association guidelines recommend testing three or more times a day which results in a minimum of 1,095 finger sticks per year. Because of the cost, pain, and inconvenience of needle sticks, many diabetics do not follow the rigorous monitoring schedule necessary for maintaining healthy blood glucose levels. Continuous glucose monitoring systems provide an alternative, real-time method for metabolic control. However, the reliability and resulting clinical utility of continuous glucose monitors is limited due the body's adverse response to subcutaneous implants. Current scientific knowledge regarding nitric oxide's role in reducing inflammation, preventing scar tissue formation, and increasing new blood vessel formation suggests that nitric oxide-releasing surfaces may create an optimal tissue environment to improve the accuracy of continuous glucose monitors. The purpose of this project is to create a nitric oxide-releasing device coating, using Novan's proprietary nitric oxide-releasing nanoparticle technology (Nitricil(tm)), to reduce the foreign body response that occurs upon implantation of subcutaneous glucose sensors. Through this two year, Phase I SBIR the Company aims to: 1) evaluate the foreign body response of Nitricil(tm) coated platinum wires in a rabbit animal model as a function of nitric oxide concentration and release kinetics;2) fabricate four layer enzymatic glucose sensors using the optimized Nitricil(tm) coating from Aim 1 and evaluate sensor response using a <10% loss in sensitivity, response time, and/or linearity as pass/fail criteria;and 3) demonstrate the stability of both the nitric oxide-releasing coating and the enzyme-based sensor function on terminally sterilized sensors over time. Following the completion of Phase I milestones, Novan will explore the scale up of sensor dip-coating procedures, apply the coating to commercially available devices provided by a corporate partner, evaluate the biocompatibility of finished glucose sensors according to ISO-10993 and FDA guidelines, and conduct proof-of-concept testing of the Nitricil(tm)- coated glucose sensor in porcine animal models to establish mean absolute percent deviation from blood glucose levels.