title: Surfactants, not size or zeta-potential influence blood-brain barrier passage of polymeric nanoparticles.
abstract: Nanoparticles (NP) can deliver drugs across the blood-brain barrier (BBB), but little is known which of the factors surfactant, size and zeta-potential are essential for allowing BBB passage. To this end we designed purpose-built fluorescent polybutylcyanoacrylate (PBCA) NP and imaged the NP's passage over the blood-retina barrier - which is a model of the BBB - in live animals. Rats received intravenous injections of fluorescent PBCA-NP fabricated by mini-emulsion polymerisation to obtain various NP's compositions that varied in surfactants (non-ionic, anionic, cationic), size (67-464nm) and zeta-potential. Real-time imaging of retinal blood vessels and retinal tissue was carried out with in vivo confocal neuroimaging (ICON) before, during and after NP's injection. Successful BBB passage with subsequent cellular labelling was achieved if NP were fabricated with non-ionic surfactants or cationic stabilizers but not when anionic compounds were added. NP's size and charge had no influence on BBB passage and cell labelling. This transport was not caused by an unspecific opening of the BBB because control experiments with injections of unlabelled NP and fluorescent dye (to test a "door-opener" effect) did not lead to parenchymal labelling. Thus, neither NP's size nor chemo-electric charge, but particle surface is the key factor determining BBB passage. This result has important implications for NP engineering in medicine: depending on the surfactant, NP can serve one of two opposite functions: while non-ionic tensides enhance brain up-take, addition of anionic tensides prevents it. NP can now be designed to specifically enhance drug delivery to the brain or, alternatively, to prevent brain penetration so to reduce unwanted psychoactive effects of drugs or prevent environmental nanoparticles from entering tissue of the central nervous system.
authors.affiliation: Institute of Medical Psychology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Voigt
authors.affiliation: Institute of Medical Psychology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Henrich-Noack
authors.affiliation: Institute of Process Engineering, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kockentiedt
authors.affiliation: Institute of Process Engineering, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Hintz
authors.affiliation: Institute of Process Engineering, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Tomas
authors.affiliation: Institute of Medical Psychology, Otto-von-Guericke University, Magdeburg, Germany. Electronic address: imp@med.ovgu.de.
authors.forename: Bernhard A
authors.initials: BA
authors.lastname: Sabel
mesh_terms: D000327:Adsorption; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001813:Blood-Retinal Barrier / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004655:Emulsions; D007275:Injections, Intravenous; D007700:Kinetics; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D059906:Neuroimaging; D010316:Particle Size; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics; D011919:Rats, Inbred Strains; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D011108:Polymers; D013501:Surface-Active Agents
keywords: Blood–brain barrier; Cellular uptake of nanoparticles; In vivo imaging; Polybutylcyanoacrylate nanoparticles; Surfactants; Zeta-potential