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Facilitation of Drug Transport across the Blood–Brain Barrier with Ultrasound and Microbubbles

Department of Neurology, University Medicine Mannheim, Heidelberg University, 68167 Mannheim, Germany
Academic Editor: Gert Fricker
Pharmaceutics 2015, 7(3), 275-293;
Received: 31 March 2015 / Revised: 13 August 2015 / Accepted: 14 August 2015 / Published: 31 August 2015
(This article belongs to the Special Issue Drug Delivery to Brain)
PDF [924 KB, uploaded 31 August 2015]


Medical treatment options for central nervous system (CNS) diseases are limited due to the inability of most therapeutic agents to penetrate the blood–brain barrier (BBB). Although a variety of approaches have been investigated to open the BBB for facilitation of drug delivery, none has achieved clinical applicability. Mounting evidence suggests that ultrasound in combination with microbubbles might be useful for delivery of drugs to the brain through transient opening of the BBB. This technique offers a unique non-invasive avenue to deliver a wide range of drugs to the brain and promises to provide treatments for CNS disorders with the advantage of being able to target specific brain regions without unnecessary drug exposure. If this method could be applied for a range of different drugs, new CNS therapeutic strategies could emerge at an accelerated pace that is not currently possible in the field of drug discovery and development. This article reviews both the merits and potential risks of this new approach. It assesses methods used to verify disruption of the BBB with MRI and examines the results of studies aimed at elucidating the mechanisms of opening the BBB with ultrasound and microbubbles. Possible interactions of this novel delivery method with brain disease, as well as safety aspects of BBB disruption with ultrasound and microbubbles are addressed. Initial translational research for treatment of brain tumors and Alzheimer’s disease is presented. View Full-Text
Keywords: blood–brain barrier; focused ultrasound; CNS disease; microbubbles; safety blood–brain barrier; focused ultrasound; CNS disease; microbubbles; safety

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Meairs, S. Facilitation of Drug Transport across the Blood–Brain Barrier with Ultrasound and Microbubbles. Pharmaceutics 2015, 7, 275-293.

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