A1 Refereed original research article in a scientific journal

The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium




AuthorsFrancisca Araújo, Neha Shrestha, Mohammed-Ali Shahbazi, Pedro Fonte, Ermei M. Mäkilä, Jarno J. Salonen, Jouni T. Hirvonen, Pedro L. Granja, Hélder A. Santos, Bruno Sarmento

PublisherElsevier Ltd

Publication year2014

JournalBiomaterials

Journal name in sourceBiomaterials

Volume35

Issue33

First page 9199

Last page9207

Number of pages9

ISSN1878-5905

DOIhttps://doi.org/10.1016/j.biomaterials.2014.07.026

Web address http://api.elsevier.com/content/abstract/scopus_id:84906788144


Abstract

Glucagon like peptide-1 (GLP-1) is an incretin hormone that is in the pipeline for type 2 diabetes mellitus (T2DM) therapy. However, oral administration of GLP-1 is hindered by the harsh conditions of the gastrointestinal tract and poor bioavailability. In this study, three nanosystems composed by three different biomaterials (poly(lactide-co-glycolide) polymer (PLGA), Witepsol E85 lipid (solid lipid nanoparticles, SLN) and porous silicon (PSi) were developed and loaded with GLP-1 to study their permeability invitro. All the nanoparticles presented a size of approximately 200nm. The nanoparticles' interaction with the mucus and the intestinal cells were enhanced after coating with chitosan (CS). PSi nanosystems presented the best association efficiency (AE) and loading degree (LD), even though a high AE was also observed for PLGA nanoparticles and SLN. Among all the nanosystems, PLGA and PSi were the only nanoparticles able to sustain the release of GLP-1 in biological fluids when coated with CS. This characteristic was also maintained when the nanosystems were in contact with the intestinal Caco-2 and HT29-MTX cell monolayers. The CS-coated PSi nanoparticles showed the highest GLP-1 permeation across the intestinal invitro models. In conclusion, PLGA+CS and PSi+CS are promising nanocarriers for the oral delivery of GLP-1. © 2014 Elsevier Ltd.




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