Design of insulin delivery devices based on glucose sensitive membranes

Abstract

A theoretical model has been developed to evaluate possible designs for an insulin delivery system which is responsive to glucose. The system is based upon a glucose sensitive hydrogel containing immobilized glucose oxidase and catalase. The requirement of molecular oxygen for the enzymic reactions ordinarily limits the response of the system to levels of glucose (less than 50 mg%) below the patho-physiological range (50–1000 mg%) The theoretical model dcveloned desrnbes the transient as well as steady state diffusion and reaction of glucose, oxygen and gluconic acid within the macroporous hydrogel for various designs chosen to alleviate the oxygen limitation. The designs are evaluated in terms of the average pH change within the gel in response to increasing concentrations of glucose. The model predicts the oxygen limitation that has been seen experimentally for a thin glucose sensitive membrane (GSM). The modeling studies have also revealed four device configurations that overcome this limitation. Each design uses silicone rubber to create additional pathways for oxygen delivery to the gel interior. A thin GSM loaded with insulin and placed over a silicone rubber drum, sealed to form a gaseous reservoir, was found to be sensitive to glucose concentrations in the 0–500 mg% range. A second design using a silicone rubber tube filled with GSM (also preloaded with insulin), exhibited glucose sensitivity in the 0–400 mg% range. A combined design, with a central gaseous reservoir bounded by plugs of GSM in a silicone rubber tube, retained a linear response even in the 300–500 rag% range. Finally a fourth design, with an insulin loaded GSM sandwiched between two circular films of silicone rubber sheeting, was sensitive in the 0–200 mg% range. Further considerations of response time, insulin loading and delivery capacity are also discussed.