Absorption and efficiency of insulin after oral administration of insulin-loaded nanocapsules in diabetic rats.
Poly(isobutylcyanoacrylate) nanocapsules have been shown to decrease the blood glucose level after oral administration to streptozotocin-induced diabetic fasted rats after 2 days [Diabetes 37 (1988) 246]. Yet, the absorption of insulin in the blood of rats has not been characterised. The aim of this work was to evaluate the biological activity of insulin given orally as nanocapsules. Humalog-loaded nanocapsules (50 IU/kg) were administered by gavage to streptozotocin-induced diabetic rats. Thirty minutes to 1 h after oral administration, significant levels of human insulin were detected in rat plasma. However, the concentrations were very heterogenous from one rat to another and no decrease of glycemia could be observed. In addition, parenteral injection of insulin in solution showed that high levels of the protein are necessary to decrease blood glucose concentration in diabetic rats. These concentrations were not reached after oral administration. The same dose of insulin decreased glycemia by 50% in normal rats and by only 25% in diabetics. This suggested that an insulino-resistance was developed by streptozotocin-induced diabetic rats.
Cournarie
F
F
Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie UMR CNRS 8612, Université Paris XI, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92 296 Cedex, Châtenay-Malabry, France.
Auchere
D
D
Chevenne
D
D
Lacour
B
B
Seiller
M
M
Vauthier
C
C
D000818:Animals; D001682:Biological Availability; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004343:Drug Implants; D006946:Hyperinsulinism / Q000097:blood; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007408:Intestinal Absorption; D008863:Microspheres; D051381:Rats
D004343:Drug Implants; D007004:Hypoglycemic Agents; D007328:Insulin