Oral hypoglycaemic effect of GLP-1 and DPP4 inhibitor based nanocomposites in a diabetic animal model

: Neha Shrestha, Francisca Araújo, Mohammad-Ali Shahbazi, Ermei Mäkilä, Maria João Gomes, Mikko Airavaara, Esko I. Kauppinen, Janne Raula, Jarno Salonen, Jouni Hirvonen, Bruno Sarmento, Hélder A. Santos

Publisher: ELSEVIER SCIENCE BV

: 2016

: Journal of Controlled Release

: JOURNAL OF CONTROLLED RELEASE

: J CONTROL RELEASE

: 232

: 113

: 119

: 7

: 0168-3659

: 1873-4995

DOI: https://doi.org/10.1016/j.jconrel.2016.04.024

Glucagon-like peptide-1 (GLP-1), an incretin hormone, is used for type 2 diabetes mellitus (T2DM) treatment because of its ability to stimulate insulin secretion and release in a glucose-dependent manner. Despite of its potent insulinotropic effect, oral GLP-1 delivery is greatly limited by its instability in the gastrointestinal tract, poor absorption efficiency and rapid degradation by dipeptidylpeptidase-4 (DPP4) enzyme leading to a short half-life (similar to 2min). Thus, a multistage dual-drug delivery nanosystem was developed to deliver GLP-1 and DPP4 inhibitor simultaneously. The system comprised of chitosan-modified porous silicon (CSUn) nanoparticles, which were coated by an enteric polymer, hydroxypropylmethylcellulose acetate succinate MF, using aerosol flow reactor technology. A non-obese T2DM rat model induced by co-administration of nicotinamide and streptozotocin was used to evaluate the in vivo efficacy of the nanosystem. The oral administration of H-CSUn nanoparticles resulted in 32% reduction in blood glucose levels and similar to 6.0-fold enhancement in pancreatic insulin content, as compared to the GLP-1 + DPP4 inhibitor solution. Overall, these results present a promising system for oral co-delivery of GLP-1 and DPP4 inhibitor that could be further evaluated in a chronic diabetic study. (C) 2016 Elsevier B.V. All rights reserved.