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

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

26 Citations (Scopus)

Abstract

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 (~ 2 min). 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 ~ 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.

Original languageEnglish
Pages (from-to)113-119
Number of pages7
JournalJournal of Controlled Release
Volume232
DOIs
Publication statusPublished - 28 Jun 2016
MoE publication typeA1 Journal article-refereed

Keywords

  • Chitosan
  • Dipeptidyl peptidase-4
  • Ex vivo
  • Glucagon-like peptide-1
  • In vivo
  • Oral delivery
  • Porous silicon nanoparticles

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