Prolonged Release of Insulin by Cholesterol-Matrix Implant

Insulin dispersed in a pellet disk made by compressing an admixture with cholesterol was found to reduce hyperglycemia in streptozocin-induced diabetic Wistar rats. I evaluated the effect of insulin content. At 3% insulin, two pieces of quarter-disk implant (∼50 mg each) lowered blood glucose levels from >22 mM to 17.5 mM for only 3 days. Normalization of hyperglycemia was sustained from ∼10 days for the implant with 6% insulin content and to 24 ± 5 days for 8–10% insulin in the composition. Insulin content up to 50% resulted in hypoglycemia and shorter implant service life. Not all of the pellet disks prepared were active, especially those with 3% insulin content. However, when broken further into 1-mm³ chips, all became active, with onset of action in <2 h, and the extent of hyperglycemia reduction was reproducible. Three successive subcutaneous insertions of ∼80 mg chips with 10% insulin maintained normoglycemia for 2.5 mo. Because the implant materials are constituents of tissue, no biocompatibility problem is expected.