title: Nanoparticle delivery to the brain--By focused ultrasound and self-assembled nanoparticle-stabilized microbubbles.
abstract: The blood-brain barrier (BBB) constitutes a significant obstacle for the delivery of drugs into the central nervous system (CNS). Nanoparticles have been able to partly overcome this obstacle and can thus improve drug delivery across the BBB. Furthermore, focused ultrasound in combination with gas filled microbubbles has opened the BBB in a temporospatial manner in animal models, thus facilitating drug delivery across the BBB. In the current study we combine these two approaches in our quest to develop a novel, generic method for drug delivery across the BBB and into the CNS. Nanoparticles were synthesized using the polymer poly(butyl cyanoacrylate) (PBCA), and such nanoparticles have been reported to cross the BBB to some extent. Together with proteins, these nanoparticles self-assemble into microbubbles. Using these novel microbubbles in combination with focused ultrasound, we successfully and safely opened the BBB transiently in healthy rats. Furthermore, we also demonstrated that the nanoparticles could cross the BBB and deliver a model drug into the CNS.
authors.affiliation: Department of Physics, Norwegian University of Science and Technology, 7491 Trondheim, Norway. Electronic address: andreas.aslund@ntnu.no.
authors.forename: Andreas K O
authors.initials: AKO
authors.lastname: Åslund
authors.affiliation: SINTEF Technology and Society, P.O. box 4760 Sluppen, 7465 Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Berg
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Hak
authors.affiliation: SINTEF Materials and Chemistry, P.O. box 4760 Sluppen, 7465 Trondheim, Norway.
authors.forename: Ýrr
authors.initials: Ý
authors.lastname: Mørch
authors.affiliation: Department of Pathology and Medical Genetics, St.Olavs University Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Sverre H
authors.initials: SH
authors.lastname: Torp
authors.affiliation: Department of Neuroscience, Norwegian University of Science and Technology, 7491 Trondheim, Norway; Division of Pharmacology and Clinical Neuroscience, Department of Neurosurgery, Umeå University Hospital, Umeå, Sweden.
authors.forename: Axel
authors.initials: A
authors.lastname: Sandvig
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Marius
authors.initials: M
authors.lastname: Widerøe
authors.affiliation: SINTEF Technology and Society, P.O. box 4760 Sluppen, 7465 Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Rune
authors.initials: R
authors.lastname: Hansen
authors.affiliation: Department of Physics, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Catharina
authors.initials: C
authors.lastname: de Lange Davies
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002199:Capillary Permeability; D004337:Drug Carriers; D004339:Drug Compounding; D004659:Enbucrilate / Q000737:chemistry*; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D045423:Microbubbles; D053758:Nanoparticles; D036103:Nanotechnology; D010078:Oxazines / Q000737:chemistry / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D014465:Ultrasonics / Q000379:methods*
chemical_list: D004337:Drug Carriers; D005456:Fluorescent Dyes; D010078:Oxazines; D004659:Enbucrilate; C044808:nile red
keywords: Blood–brain barrier; Drug delivery; Focused ultrasound; Microbubble; Nanoparticle; PBCA