Journal
BIOMATERIALS
Volume 35, Issue 33, Pages 9199-9207Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.07.026
Keywords
Glucagon like peptide-1; Oral delivery systems; Nanoparticles; Chitosan; Triple co-culture; Diabetes
Funding
- European Regional Development Fund (ERDF) through the Programa Operacional Factores de Competitividade - COMPETE
- Portuguese funds through Fundacao para a Ciencia e a Tecnologia (FCT) [PEst-C/SAU/LA0002/2013]
- North Portugal Regional Operational Programme under National Strategic Reference Framework (NSRF) [SAESCTN-PIICDT/2011]
- FCT [SFRH/BD/87016/2012]
- Academy of Finland [252215]
- University of Helsinki Research Funds
- Biocentrum Helsinki
- Finnish Center [TM-13-9048]
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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 in vitro. All the nanoparticles presented a size of approximately 200 nm. 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 in vitro models. In conclusion, PLGA + CS and PSi + CS are promising nanocarriers for the oral delivery of GLP-1. (C) 2014 Elsevier Ltd. All rights reserved.
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