title: A relevant in vitro rat model for the evaluation of blood-brain barrier translocation of nanoparticles.
abstract: Poly(MePEG2000cyanoacrylate-co-hexadecylcyanoacrylate) (PEG-PHDCA) nanoparticles have demonstrated their capacity to reach the rat central nervous system after intravenous injection. For insight into the transport of colloidal systems across the blood-brain barrier (BBB), we developed a relevant in vitro rat BBB model consisting of a coculture of rat brain endothelial cells (RBECs) and rat astrocytes. The RBECs used in our model displayed and retained structural characteristics of brain endothelial cells, such as expression of P-glycoprotein, occludin and ZO-1, and immunofluorescence studies showed the specific localization of occludin and ZO1. The high values of transendothelial electrical resistance and low permeability coefficients of marker molecules demonstrated the functionality of this model. The comparative passage of polyhexadecylcyanoacrylate and PEG-PHDCA nanoparticles through this model was investigated, showing a higher passage of PEGylated nanoparticles, presumably by endocytosis. This result was confirmed by confocal microscopy. Thanks to a good in vitro/in vivo correlation, this rat BBB model will help in understanding the mechanisms of nanoparticle translocation and in designing new types of colloidal carriers as brain delivery systems.
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmacy, UMR CNRS 8612, Faculty of Pharmacy, University of Paris-XI, 92296 Châtenay-Malabry, France.
authors.forename: E
authors.initials: E
authors.lastname: Garcia-Garcia
authors.forename: S
authors.initials: S
authors.lastname: Gil
authors.forename: K
authors.initials: K
authors.lastname: Andrieux
authors.forename: D
authors.initials: D
authors.lastname: Desmaële
authors.forename: V
authors.initials: V
authors.lastname: Nicolas
authors.forename: F
authors.initials: F
authors.lastname: Taran
authors.forename: D
authors.initials: D
authors.lastname: Georgin
authors.forename: J P
authors.initials: JP
authors.lastname: Andreux
authors.forename: F
authors.initials: F
authors.lastname: Roux
authors.forename: P
authors.initials: P
authors.lastname: Couvreur
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002199:Capillary Permeability; D003487:Cyanoacrylates / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D036103:Nanotechnology; D062793:Occludin; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003487:Cyanoacrylates; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; C121140:polyethyleneglycol polyhexadecylylcyanoacrylate copolymer; D011092:Polyethylene Glycols