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The stimulation of GLP-1 secretion and delivery of GLP-1 agonists &ITvia&IT nanostructured lipid carriers
Catholic Univ Louvain, Louvain Drug Res Inst, Adv Drug Delivery & Biomat, B-1200 Brussels, Belgium..
Catholic Univ Louvain, Louvain Drug Res Inst, Adv Drug Delivery & Biomat, B-1200 Brussels, Belgium..
Catholic Univ Louvain, Louvain Drug Res Inst, Adv Drug Delivery & Biomat, B-1200 Brussels, Belgium..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
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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
2018. Vol. 10, no 2, p. 603-613
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Chemical Sciences Physical Sciences
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URN: urn:nbn:se:uu:diva-341488DOI: 10.1039/c7nr07736jISI: 000419152600012PubMedID: 29235598OAI: oai:DiVA.org:uu-341488DiVA, id: diva2:1186433
Available from: 2018-02-28 Created: 2018-02-28 Last updated: 2018-02-28Bibliographically approved

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Lundquist, PatrikArtursson, Per

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