Orally administered, insulin-loaded amidated pectin hydrogel beads sustain plasma concentrations of insulin in streptozotocin-diabetic rats

We report successful oral administration of insulin entrapped in amidated pectin hydrogel beads in streptozotocin (STZ)-diabetic rats, with a concomitant reduction in plasma glucose concentration. The pectin-insulin (PI) beads were prepared by the gelation of humilin-pectin solutions in the presence of calcium. Separate groups of STZ-diabetic rats were orally administered two PI beads (30 mu g insulin) once or twice daily or three beads (46 mu g) once daily for 2 weeks. Control non-diabetic and STZ-diabetic rats were orally administered pectin hydrogel drug-free beads. By comparison with control non-diabetic rats, untreated STZ-diabetic rats exhibited significantly low plasma insulin concentration (0.32 +/- 0.03ng/ml, n=6, compared with 2.60 +/- 0.44 ng/ml in controls, n=6) and increased plasma glucose concentrations (25.84 +/- 1.44 mmol/l compared with 10.72 +/- 0.52 mmol/l in controls). Administration of two PI beads twice daily (60 mu g active insulin) or three beads (46 mu g) once a day to STZ-diabetic rats increased plasma insulin concentrations (0.89 +/- 0.09 ng/ml and 1.85 +/- 0.26 ng/ml, respectively), with a concomitant reduction in plasma glucose concentration (15.45 +/- 1.63 mmol/l and 10.56 +/- 0.26 mmol/l, respectively). However, a single dose of PI beads (30 mu g) did not affect plasma insulin concentrations, although plasma glucose concentrations (17.82 +/- 2.98 mmol/l) were significantly reduced compared with those in untreated STZ-diabetic rats. Pharmacokinetic parameters in STZ-diabetic rats show that the orally administered PI beads (30 mu g insulin) were more effective in sustaining plasma insulin concentrations than was s.c. insulin (30 mu g). The data from this study suggest that this insulin-loaded amidated pectin hydrogel bead formulation not only produces sustained release of insulin, but may also reduce plasma glucose concentration in diabetes mellitus.