Format

Send to

Choose Destination
Gut. 2019 Aug 10. pii: gutjnl-2019-319146. doi: 10.1136/gutjnl-2019-319146. [Epub ahead of print]

Novel strategy for oral peptide delivery in incretin-based diabetes treatment.

Author information

1
Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute (LDRI), UCLouvain, Université catholique de Louvain, Bruxelles, Belgium.
2
Metabolism and Nutrition Research group, Louvain Drug Research Institute (LDRI), UCLouvain, Université catholique de Louvain, Brussels, Belgium.
3
WELBIO, Walloon Excellence in Life Sciences and BIOtechnology, Brussels, Belgium.
4
Metabolism and Nutrition Research group, Louvain Drug Research Institute (LDRI), UCLouvain, Université catholique de Louvain, Brussels, Belgium patrice.cani@uclouvain.be ana.beloqui@uclouvain.be.
5
Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute (LDRI), UCLouvain, Université catholique de Louvain, Bruxelles, Belgium patrice.cani@uclouvain.be ana.beloqui@uclouvain.be.

Abstract

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.

KEYWORDS:

GLP-1; bioavailability; diabetes; nanocarriers; steatosis

PMID:
31401561
DOI:
10.1136/gutjnl-2019-319146
Free full text

Conflict of interest statement

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

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center