Article Text

Download PDFPDF

Original research
Novel strategy for oral peptide delivery in incretin-based diabetes treatment
  1. Yining Xu1,
  2. Matthias Van Hul2,3,
  3. Francesco Suriano2,3,
  4. Véronique Préat1,
  5. Patrice D Cani2,3,
  6. Ana Beloqui1
  1. 1 Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute (LDRI), UCLouvain, Université catholique de Louvain, Bruxelles, Belgium
  2. 2 Metabolism and Nutrition Research group, Louvain Drug Research Institute (LDRI), UCLouvain, Université catholique de Louvain, Brussels, Belgium
  3. 3 WELBIO, Walloon Excellence in Life Sciences and BIOtechnology, Brussels, Belgium
  1. Correspondence to Professor Patrice D Cani, Louvain Drug Research Institute, WELBIO, UCLouvain, Universite catholique de Louvain, Brussels 1200, Belgium; patrice.cani{at}; Professor Ana Beloqui, Louvain Drug Research Institute, UCLouvain, Universite catholique de Louvain, Bruxelles 1200, Belgium; ana.beloqui{at}


Objective To fulfil an unmet therapeutic need for treating type 2 diabetes by developing an innovative oral drug delivery nanosystem increasing the production of glucagon-like peptide-1 (GLP-1) and the absorption of peptides into the circulation.

Design We developed a nanocarrier for the oral delivery of peptides using lipid-based nanocapsules. We encapsulated the GLP-1 analogue exenatide within nanocapsules and investigated in vitro in human L-cells (NCl-H716) and murine L-cells (GLUTag cells) the ability of the nanosystem to trigger GLP-1 secretion. The therapeutic relevance of the nanosystem in vivo was tested in high-fat diet (HFD)-induced diabetic mice following acute (one administration) or chronic treatment (5 weeks) in obese and diabetic mice.

Results We demonstrated that this innovative nanosystem triggers GLP-1 secretion in both human and murine cells as well as in vivo in mice. This strategy increases the endogenous secretion of GLP-1 and the oral bioavailability of the GLP-1 analogue exenatide (4% bioavailability with our nanosystem).

The nanosystem synergizes its own biological effect with the encapsulated GLP-1 analogue leading to a marked improvement of glucose tolerance and insulin resistance (acute and chronic). The chronic treatment decreased diet-induced obesity, fat mass, hepatic steatosis, together with lower infiltration and recruitment of immune cell populations and inflammation.

Conclusion We developed a novel nanosystem compatible with human use that synergizes its own biological effect with the effects of increasing the bioavailability of a GLP-1 analogue. The effects of the formulation were comparable to the results observed for the marketed subcutaneous formulation. This nanocarrier-based strategy represents a novel promising approach for oral peptide delivery in incretin-based diabetes treatment.

  • nanocarriers
  • diabetes
  • GLP-1
  • steatosis
  • bioavailability

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

View Full Text

Statistics from


  • Contributors Conceptualisation, AB and PDC; Methodology, YX, AB, MVH, FS and PDC; Investigations, YX, VP, AB, PDC; Resources, AB and PDC; Writing-original draft, YX and AB; Supervision, AB and PDC; Funding, AB, VP and PDC.

  • Funding YX is the recipient of a grant from the China Scholarship Council (CSC). AB is a research associate from the FRS-FNRS (Fonds de la Recherche Scientifique) Belgium. This work was supported by the Fonds de la Recherche Scientifique-FNRS under Grants n°J.0220.16 (recipient V.P.) and T.0013.19 (recipient AB). PDC is senior research associate from FRS-FNRS under grants: WELBIO-CR-2017-C02 and The Excellence Of Science (EOS 30770923) and is a recipient of the Funds Baillet Latour (Grant for Medical Research 2015).

  • Competing interests PDC is a co-founder of A-Mansia Biotech SA.

  • Patient consent for publication Not required.

  • Ethics approval All animal experiments were approved by and performed in accordance with the local animal committee (2014/UCL/MD/033 and 2017/UCL/MD/005) and as specified by the Belgian Law of 29 May 2013 on the protection of laboratory animals.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.