CONCANAVALIN-A MICROSPHERES FOR A SELF-REGULATING INSULIN DELIVERY SYSTEM

A self-regulating insulin delivery system based on the competitive binding of glucose and p-succinylamidophenyl-alpha-D-glycopyranoside-insulin (SAPG-insulin) to crosslinked concanavalin A (Con A) microspheres (MSs) has been investigated. Con A MSs prepared by a water-in-oil emulsion technique demonstrated properties of binding to glucose and SAPG-insulin (binding constants of 1.25 x 10(3) and 1.28 x 10(4) M-1, respectively) that are similar to the literature values of these properties for unmodified Con A. The retained binding capacity (number of binding sites per molecule) of Con A MSs, produced with 20% of the epsilon-amino groups crosslinked, was approximately 28% that of intact Con A. As a new device, Con A MSs loaded with SAPG-insulin was enclosed in a heat-sealed, surface-modified, porous poly(vinylidene difluoride) membrane pouch. This system showed a pulsatile release pattern for insulin with a short lag time in response to glucose challenges of 50-500 mg/dL. The pattern of release of SAPG-insulin from the devices was studied with varying design parameters, such as surface area, membrane pore size, and loading content of SAPG-insulin.