title: The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium.
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 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.
authors.affiliation: INEB - Instituto de Engenharia Biomédica, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; ICBAS - Instituto Ciências Biomédicas 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.
authors.forename: Francisca
authors.initials: F
authors.lastname: Araújo
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Neha
authors.initials: N
authors.lastname: Shrestha
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Mohammed-Ali
authors.initials: MA
authors.lastname: Shahbazi
authors.affiliation: INFACTS - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Superior de Ciências da Saúde-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.
authors.forename: Pedro
authors.initials: P
authors.lastname: Fonte
authors.affiliation: 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.
authors.forename: Ermei M
authors.initials: EM
authors.lastname: Mäkilä
authors.affiliation: Laboratory of Industrial Physics, Department of Physics and Astronomy, FI-20014 University of Turku, Finland.
authors.forename: Jarno J
authors.initials: JJ
authors.lastname: Salonen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Jouni T
authors.initials: JT
authors.lastname: Hirvonen
authors.affiliation: INEB - Instituto de Engenharia Biomédica, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; ICBAS - Instituto Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, 4050-313 Porto, Portugal.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Granja
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: helder.santos@helsinki.fi.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
authors.affiliation: INEB - Instituto de Engenharia Biomédica, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; INFACTS - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Superior de Ciências da Saúde-Norte, Department of Pharmaceutical Sciences, CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal. Electronic address: bruno.sarmento@ineb.up.pt.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells; D002470:Cell Survival; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry / Q000493:pharmacokinetics*; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D009092:Mucous Membrane / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D010316:Particle Size; D010539:Permeability; D011098:Polyglactin 910 / Q000737:chemistry; D016062:Porosity; D012825:Silicon / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D011098:Polyglactin 910; D052216:Glucagon-Like Peptide 1; D048271:Chitosan; D012825:Silicon
keywords: Chitosan; Diabetes; Glucagon like peptide-1; Nanoparticles; Oral delivery systems; Triple co-culture