title: Shuttle-mediated nanoparticle transport across an in vitro brain endothelium under flow conditions.
abstract: The blood brain barrier (BBB) represents a challenge in the development of new nano-delivery systems able to reach the central nervous system (CNS). In order to test the efficacy of these nanocarriers, it is fundamental to use in vitro models that resemble the in vivo cell culture conditions. Here, we demonstrate for the first time the ability of a membranotropic peptide, namely gH625, to transport a cargo-acting as a shuttle-across the BBB layer under flow conditions that mimic the blood flow rate. To this aim, a BBB microfluidic device was designed based on a transparent polyester porous membrane sandwiched between a top and a bottom overlying channel made of poly(methyl methacrylate) (PMMA). Our data clearly indicate that this microfluidic system allows the growth of brain endothelial bEnd.3 cells and the formation of a confluent layer at 7 days of culture that hinders the passage of nanoparticles compared to porous membrane alone. The device was validated at a 5 μL/min working flow rate, where the capability of the model to remain intact after nanoparticle passage was shown. Very interestingly, the decoration with the gH625 peptide enhances the adhesion of nanoparticles to the endothelial layer and the BBB crossing in flow conditions, thus confirming the efficacy of the gH625 as a delivery platform to the brain. Biotechnol. Bioeng. 2017;114: 1087-1095. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Center for Advanced Biomaterial for Health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, Napoli, Italy.
authors.forename: Andrea P
authors.initials: AP
authors.lastname: Falanga
authors.affiliation: Center for Advanced Biomaterial for Health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, Napoli, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pitingolo
authors.affiliation: Center for Advanced Biomaterial for Health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, Napoli, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Celentano
authors.affiliation: Center for Advanced Biomaterial for Health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, Napoli, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Cosentino
authors.affiliation: Center for Advanced Biomaterial for Health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, Napoli, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Melone
authors.affiliation: Center for Advanced Biomaterial for Health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, Napoli, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Vecchione
authors.affiliation: Center for Advanced Biomaterial for Health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, Napoli, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Guarnieri
authors.affiliation: Center for Advanced Biomaterial for Health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, Napoli, Italy.|Centro di Ricerca Interdipartimentale sui Biomateriali (CRIB), Università di Napoli Federico II, Napoli, Italy.|Dipartimento di Ingegneria, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Netti
mesh_terms: D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002460:Cell Line; D004867:Equipment Design; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation; D008954:Models, Biological; D053758:Nanoparticles / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010455:Peptides
keywords: blood brain barrier; flow conditions; membranotropic peptides; microfluidics; nanoparticles