CLOSED LOOP BIOERODIBLE INSULIN DELIVERY DEVICE

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The objective is to continue the development of a bioerodible insulin-containing implant capable of releasing insulin at kinetics that are controlled by external glucose concentration. Principally for safety reasons we are developing a dual implant. One implant delivers insulin at a predetermined rate that is independent of external glucose concentration, and the other implant delivers insulin in response to external glucose and is designed to supplement the amount delivered by the first implant when glucose levels rise above the normal 100 mg%. Both devices use a pH-sensitive poly(ortho ester) system. The insulin and glucose oxidase are dispersed within the matrix of the glucose-sensitive polymer, and the erosion rate of the polymer changes as a consequence of changing concentrations of gluconic acid generated in the surface layers of the device by the oxidation of glucose by glucose oxidase. To achieve the desired pH sensitivity of the poly(ortho ester) system, we incorporated tertiary amine functions into the polymer backbone. Both devices are fabricated by first preparing a linear ketene acetal-terminated prepolymer that is a viscous liquid at room temperature, dispersing it into the prepolymer insulin and glucose oxidase (if used) along with triol crosslinker, and curing at 40 degree C overnight. No denaturation of the proteins occurs at those mild conditions. Once a working polymer system has ben developed, it will be characterized by in vitro studies a unique computer programmable perifusion/perfusion system followed by in vivo studies using diabetic rats.