RELEASE OF INSULIN FROM PH-SENSITIVE POLY(ORTHO ESTERS)

The principal objective of this work is the development of a bioerodible insulin delivery device that will release insulin in response to the concentration of external glucose where release of insulin is modulated by pH changes resulting from a glucose-glucose oxidase reaction. A major component of such a delivery system is a bioerodible polymer that can reversibly change erosion rates in response to very small changes in the surrounding pH. We have prepared such a polymer by incorporating tertiary amine groups into a linear poly(ortho ester). When insulin is incorporated into this polymer and thin disks subjected to well defined pH pulses, the polymer responds rapidly and reversibly to these pH pulses. Current efforts involve preparation of glucose sensitive devices by surrounding the insulin-containing polymer with a microporous hydrogel containing immobilized glucose oxidase. When glucose diffuses into the device, gluconic acid produced within the hydrogel will decrease the ambient pH thus triggering release of insulin. The hydrogel is microporous to permit rapid release of insulin from the polymer to the surrounding environment. © 1990.