Design and synthesis of glucose-sensitive insulin-releasing systems

Two kinds of glucose-sensitive insulin-releasing systems were developed. The first system is based on changes in pH, induced by an enzyme, in response of glucose. The other is based on redox reaction, catalyzed by an enzyme, in response to glucose. 1) Glucose oxidase (GOD) is immobilized on a poly (acrylic acid)-grafted porous cellulose membrane, which is prepared as a pH-sensitive membrane. In the absence of glucose, the chains of poly (acrylic acid)-grafts are rod-like, lowering the porosity of the membrane and suppressing insulin permeation. On the other hand, in the presence of glucose, gluconic acid, produced by GOD, protonates the poly (acrylic acid), making the graft chains coil-like and the pores open to enhance insulin permeation. 2) Insulin is immobilized on a membrane through disulfide bond, NAD and FAD are also coimmobilized on the membrane. When glucose is added, glucose dehydrogenase catalyzes oxidation of the glucose. Electrons, which are produced during the reaction, are transported, and subsequently they reduce the disulfide bonds. Consequently the immobilized insulin is released. © 1988, THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM. All rights reserved.