PMID- 25109441 OWN - NLM STAT- MEDLINE DCOM- 20150511 LR - 20140822 IS - 1878-5905 (Electronic) IS - 0142-9612 (Linking) VI - 35 IP - 33 DP - 2014 Nov TI - The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium. PG - 9199-207 LID - S0142-9612(14)00835-7 [pii] LID - 10.1016/j.biomaterials.2014.07.026 [doi] AB - 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. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Araujo, Francisca AU - Araujo F AD - INEB - Instituto de Engenharia Biomedica, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; ICBAS - Instituto Ciencias Biomedicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, 4050-313 Porto, Portugal; Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. FAU - Shrestha, Neha AU - Shrestha N AD - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. FAU - Shahbazi, Mohammed-Ali AU - Shahbazi MA AD - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. FAU - Fonte, Pedro AU - Fonte P AD - INFACTS - Instituto de Investigacao e Formacao Avancada em Ciencias e Tecnologias da Saude, Instituto Superior de Ciencias da Saude-Norte, Department of Pharmaceutical Sciences, CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal; REQUIMTE, Department of Chemical Sciences - Applied Chemistry Lab, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 4050-313 Porto, Portugal. FAU - Makila, Ermei M AU - Makila EM AD - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland; Laboratory of Industrial Physics, Department of Physics and Astronomy, FI-20014 University of Turku, Finland. FAU - Salonen, Jarno J AU - Salonen JJ AD - Laboratory of Industrial Physics, Department of Physics and Astronomy, FI-20014 University of Turku, Finland. FAU - Hirvonen, Jouni T AU - Hirvonen JT AD - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. FAU - Granja, Pedro L AU - Granja PL AD - INEB - Instituto de Engenharia Biomedica, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; ICBAS - Instituto Ciencias Biomedicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, 4050-313 Porto, Portugal. FAU - Santos, Helder A AU - Santos HA AD - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: helder.santos@helsinki.fi. FAU - Sarmento, Bruno AU - Sarmento B AD - INEB - Instituto de Engenharia Biomedica, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; INFACTS - Instituto de Investigacao e Formacao Avancada em Ciencias e Tecnologias da Saude, Instituto Superior de Ciencias da Saude-Norte, Department of Pharmaceutical Sciences, CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal. Electronic address: bruno.sarmento@ineb.up.pt. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140807 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (Biocompatible Materials) RN - 0 (Drug Carriers) RN - 34346-01-5 (Polyglactin 910) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9012-76-4 (Chitosan) RN - Z4152N8IUI (Silicon) SB - IM MH - Biocompatible Materials/chemistry/pharmacology MH - Caco-2 Cells MH - Cell Survival MH - Chitosan/chemistry MH - Drug Carriers/chemistry MH - Glucagon-Like Peptide 1/chemistry/*pharmacokinetics MH - HT29 Cells MH - Humans MH - Intestinal Mucosa/*drug effects/metabolism MH - Mucous Membrane/*drug effects/metabolism MH - Nanoparticles/*chemistry MH - Nanotechnology/methods MH - Particle Size MH - Permeability MH - Polyglactin 910/chemistry MH - Porosity MH - Silicon/chemistry OTO - NOTNLM OT - Chitosan OT - Diabetes OT - Glucagon like peptide-1 OT - Nanoparticles OT - Oral delivery systems OT - Triple co-culture EDAT- 2014/08/12 06:00 MHDA- 2015/05/12 06:00 CRDT- 2014/08/12 06:00 PHST- 2014/06/18 00:00 [received] PHST- 2014/07/19 00:00 [accepted] PHST- 2014/08/12 06:00 [entrez] PHST- 2014/08/12 06:00 [pubmed] PHST- 2015/05/12 06:00 [medline] AID - S0142-9612(14)00835-7 [pii] AID - 10.1016/j.biomaterials.2014.07.026 [doi] PST - ppublish SO - Biomaterials. 2014 Nov;35(33):9199-207. doi: 10.1016/j.biomaterials.2014.07.026. Epub 2014 Aug 7.