Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system.
The physiology of the vasculature in the central nervous system (CNS), which includes the blood-brain barrier (BBB) and other factors, complicates the delivery of most drugs to the brain. Different methods have been used to bypass the BBB, but they have limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Focused ultrasound (FUS), when combined with circulating microbubbles, is a noninvasive method to locally and transiently disrupt the BBB at discrete targets. This review provides insight on the current status of this unique drug delivery technique, experience in preclinical models, and potential for clinical translation. If translated to humans, this method would offer a flexible means to target therapeutics to desired points or volumes in the brain, and enable the whole arsenal of drugs in the CNS that are currently prevented by the BBB.
Department of Physics, Boston College, Chestnut Hill, USA; Department of Radiology, Brigham & Women's Hospital, Harvard Medical School, Boston, USA.
Muna
M
Aryal
Department of Radiology, Brigham & Women's Hospital, Harvard Medical School, Boston, USA.
Costas D
CD
Arvanitis
Department of Radiology, Brigham & Women's Hospital, Harvard Medical School, Boston, USA; Institute of Biomedical Engineering, Department of Engineering Science, and Brasenose College, University of Oxford, Oxford, UK.
Phillip M
PM
Alexander
Department of Radiology, Brigham & Women's Hospital, Harvard Medical School, Boston, USA. Electronic address: njm@bwh.harvard.edu.
Nathan
N
McDannold
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D014464:Ultrasonic Therapy; D014465:Ultrasonics / Q000379:methods*
Brain; Drug delivery; Microbubbles; Ultrasound