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 (approximately 50 mg each) lowered blood glucose levels from greater than 22 mM to 17.5 mM for only 3 days. Normalization of hyperglycemia was sustained from approximately 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 less than 2 h, and the extent of hyperglycemia reduction was reproducible. Three successive subcutaneous insertions of approximately 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.