title: Cellular uptake and transcytosis of lipid-based nanoparticles across the intestinal barrier: Relevance for oral drug delivery.
abstract: Oral administration is the preferred route for drug delivery and nanosystems represent a promising tool for protection and transport of hardly soluble, chemically unstable and poorly permeable drugs through the intestinal barrier. In the present work, we have studied lipid nanoparticles cellular uptake, internalization pathways and transcytosis routes through Caco-2 cell monolayers. Both lipid nanosystems presented similar size (∼180nm) and surface charge (-30mV). Nanostructured lipid carriers showed a higher cellular uptake and permeability across the barrier, but solid lipid nanoparticles could enter cells faster than the former. The internalization of lipid nanoparticles occurs mainly through a clathrin-mediated endocytosis mechanism, although caveolae-mediated endocytosis is also involved in the uptake. Both lipid nanoparticles were able to cross the intestinal barrier by a preferential transcellular route. This work contributed to a better knowledge of the developed nanosystems for the oral delivery of a wide spectrum of drugs.
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Ana Rute
authors.initials: AR
authors.lastname: Neves
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Joana Fontes
authors.initials: JF
authors.lastname: Queiroz
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Costa Lima
authors.affiliation: HEMS/IBMC - Institute for Molecular and Cell Biology, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Figueiredo
authors.affiliation: HEMS/IBMC - Institute for Molecular and Cell Biology, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Fernandes
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. Electronic address: shreis@ff.up.pt.
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
mesh_terms: D000284:Administration, Oral; D018938:Caco-2 Cells; D016503:Drug Delivery Systems; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D013499:Surface Properties; D057900:Transcytosis
chemical_list: D008055:Lipids
keywords: Caco-2 cell monolayers; Intestinal permeability; Lipid nanoparticles; Oral administration; Transcytosis