Oral Delivery of Insulin Loaded into Polymeric Nanoparticles in Rats

G.      Tosi; A.      V. Vergoni; B.      Ruozi; L.      Bondioli; F.      Forni; M.      A. Vandelli; R.      Tacchi; A.      Ferrari; L.      Spaccapelo; A.      Bertolini

Abstract

Diabetes prevalence is steadily increasing and both type 1 and type 2 contribute to this “diabetes epidemic”. Insulin is the sole therapeutic, life-saving option for type 1 diabetes with patients self-injecting the hormone every day for life. In this study, insulin has been loaded into polymeric nanoparticles (Np) of poly (D,L-lactide-co-glycolide) and different amounts of insulin-loaded Np (1, 3 or 10 I.U./kg) were administered by oral gavage to normal and diabetic rats, s.c. pre-treated with omeprazole (5 mg/Kg). In normal rats, the in vivo results highlighted a dose-related decrease of blood glucose levels in normal rats at the end of the observation period (20-50% depending on the doses of insulin delivered by Np). In diabetic rats, the dose of 3 I.U./kg produced a 50% decrease of the glycaemia 90 min after the treatment, with an effect stable up to the end of the observation period; a higher dose of insulin delivered by Np (10 I.U./kg) developed a significant decrease of glycaemia (65%). Correspondently, in diabetic rats, plasma insulin levels increased in a doserelated manner (3, 5, and 7-folds with respect to the basal level, depending on insulin doses delivered by NPs) with still significant values 2 h after administration. Thus, these Np are able, after pre-treatment with omeprazole, to transport insulin across the intestinal barrier, preserving the biological activity of the hormone in rats and if replicated in humans, it could suggest the concrete possibility of oral administration of insulin.

Keywords: Diabetes, insulin, nanoparticles, oral absorption, Zn-Insulin Loading, PLGA Nanoparticles, Ins-Np, Glycemia, Insulinemia