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The stimulation of GLP-1 secretion and delivery of GLP-1 agonists &ITvia&IT nanostructured lipid carriers
Catholic University of Louvain, Belgium.
Catholic University of Louvain, Belgium.
Catholic University of Louvain, Belgium.
Uppsala University, Sweden.
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2018 (English)In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 10, no 2, p. 603-613Article in journal (Refereed) Published
Abstract [en]

Nanoparticulate based drug delivery systems have been extensively studied to efficiently encapsulate and deliver peptides orally. However, most of the existing data mainly focus on the nanoparticles as a drug carrier, but the ability of nanoparticles having a biological effect has not been exploited. Herein, we hypothesize that nanostructured lipid carriers (NLCs) could activate the endogenous glucagon-like peptide-1 (GLP-1) secretion and also act as oral delivery systems for GLP-1 analogs (exenatide and liraglutide). NLCs effectively encapsulated the peptides, the majority of which were only released under the intestinal conditions. NLCs, with and without peptide encapsulation, showed effective induction of GLP-1 secretion in vitro from the enteroendocrinal L-cells (GLUTag). NLCs also showed a 2.9-fold increase in the permeability of exenatide across the intestinal cell monolayer. The intestinal administration of the exenatide and liraglutide loaded NLCs did not demonstrate any glucose lowering effect on normal mice. Further, ex vivo studies depicted that the NLCs mainly adhered to the mucus layer. In conclusion, this study demonstrates that NLCs need further optimization to overcome the mucosal barrier in the intestine; nonetheless, this study also presents a promising strategy to use a dual-action drug delivery nanosystem which synergizes its own biological effect and that of the encapsulated drug molecule.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY , 2018. Vol. 10, no 2, p. 603-613
National Category
Biomaterials Science
Identifiers
URN: urn:nbn:se:liu:diva-144245DOI: 10.1039/c7nr07736jISI: 000419152600012PubMedID: 29235598OAI: oai:DiVA.org:liu-144245DiVA, id: diva2:1173643
Note

Funding Agencies|European Union Seventh Framework Programme (FP7) [281035]; Marie Sklodowska-Curie actions-Standard European fellowship [751257]; FNRS [J.0220.16]

Available from: 2018-01-12 Created: 2018-01-12 Last updated: 2018-01-12

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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health Sciences
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CiteExportLink to record
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  • apa
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