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.
Pai
C M
CM
Department of Pharmaceutics, University of Utah, Salt Lake City 84108.
Bae
Y H
YH
Mack
E J
EJ
Wilson
D E
DE
Kim
S W
SW
D001667:Binding, Competitive; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003208:Concanavalin A / Q000008:administration & dosage* / Q000737:chemistry; D003432:Cross-Linking Reagents; D005960:Glucosides / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry; D007332:Insulin Infusion Systems; D008855:Microscopy, Electron, Scanning; D008863:Microspheres
D003432:Cross-Linking Reagents; D005960:Glucosides; D007328:Insulin; C066740:insulin, 4-succinylamidophenylglucopyranoside-; D003208:Concanavalin A