title: Feasibility Study of the Permeability and Uptake of Mesoporous Silica Nanoparticles across the Blood-Brain Barrier.
abstract: Drug delivery into the brain is impeded by the blood-brain-barrier (BBB) that filters out the vast majority of drugs after systemic administration. In this work, we assessed the transport, uptake and cytotoxicity of promising drug nanocarriers, mesoporous silica nanoparticles (MSNs), in in vitro models of the BBB. RBE4 rat brain endothelial cells and Madin-Darby canine kidney epithelial cells, strain II, were used as BBB models. We studied spherical and rod-shaped MSNs with the following modifications: bare MSNs and MSNs coated with a poly(ethylene glycol)-poly(ethylene imine) (PEG-PEI) block copolymer. In transport studies, MSNs showed low permeability, whereas the results of the cellular uptake studies suggest robust uptake of PEG-PEI-coated MSNs. None of the MSNs showed significant toxic effects in the cell viability studies. While the shape effect was detectable but small, especially in the real-time surface plasmon resonance measurements, coating with PEG-PEI copolymers clearly facilitated the uptake of MSNs. Finally, we evaluated the in vivo detectability of one of the best candidates, i.e. the copolymer-coated rod-shaped MSNs, by two-photon in vivo imaging in the brain vasculature. The particles were clearly detectable after intravenous injection and caused no damage to the BBB. Thus, when properly designed, the uptake of MSNs could potentially be utilized for the delivery of drugs into the brain via transcellular transport.
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.|Laboratory of Physical Chemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.|Cell Biology, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.|Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Habib
authors.initials: H
authors.lastname: Baghirov
authors.affiliation: Laboratory of Physical Chemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.|Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.
authors.forename: Didem
authors.initials: D
authors.lastname: Karaman
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Tapani
authors.initials: T
authors.lastname: Viitala
authors.affiliation: Laboratory of Physical Chemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.
authors.forename: Alain
authors.initials: A
authors.lastname: Duchanoy
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Lou
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
authors.forename: Veronika
authors.initials: V
authors.lastname: Mamaeva
authors.affiliation: Neurotar LtD, Helsinki, Finland.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Pryazhnikov
authors.affiliation: Neurotar LtD, Helsinki, Finland.
authors.forename: Leonard
authors.initials: L
authors.lastname: Khiroug
authors.affiliation: Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Catharina
authors.initials: C
authors.lastname: de Lange Davies
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.|Cell Biology, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.|Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Sahlgren
authors.affiliation: Laboratory of Physical Chemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.|Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Rosenholm
mesh_terms: D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000648:ultrastructure; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D004337:Drug Carriers; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007275:Injections, Intravenous; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D036641:Microscopy, Fluorescence, Multiphoton; D008954:Models, Biological; D057054:Molecular Imaging; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D010316:Particle Size; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry; D051381:Rats; D012822:Silicon Dioxide / Q000737:chemistry*; D020349:Surface Plasmon Resonance
chemical_list: D004337:Drug Carriers; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D011094:Polyethyleneimine