Focused ultrasound-mediated drug delivery through the blood-brain barrier.
Authors: Burgess A, Shah K, Hough O, Hynynen K
Despite recent advances in blood-brain barrier (BBB) research, it remains a significant hurdle for the pharmaceutical treatment of brain diseases. Focused ultrasound (FUS) is one method to transiently increase permeability of the BBB to promote drug delivery to specific brain regions. An introduction to the BBB and a brief overview of the methods, which can be used to circumvent the BBB to promote drug delivery, is provided. In particular, we discuss the advantages and limitations of FUS technology and the efficacy of FUS-mediated drug delivery in models of disease. MRI for targeting and evaluating FUS treatments, combined with administration of microbubbles, allows for transient, reproducible BBB opening. The integration of a real-time acoustic feedback controller has improved treatment safety. Successful clinical translation of FUS has the potential to transform the treatment of brain disease worldwide without requiring the development of new pharmaceutical agents.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To review focused ultrasound as a method to transiently increase blood–brain barrier permeability to enhance drug delivery, discussing its advantages, limitations, efficacy in disease models, and potential for clinical translation.
Animal model / Human subject
rodents and Mice
Disease model
Alzheimer's disease, Parkinson's disease, Amytrophic Lateral Sclerosis (ALS) and Multiple Sclerosis
MRI or image guidance method
MRI guidance (with real-time acoustic feedback controller)
Targeted brain region(s)
Hippocampus
Target coordinates
not provided
Cargo name and characteristics
not provided
Route of administration
intrvenous and intransanal
Outcomes and Safety
Summary of Outcomes
Focused ultrasound combined with systemically administered microbubbles and MRI targeting produces transient, reproducible opening of the blood–brain barrier to enhance region-specific drug delivery, and the addition of real-time acoustic feedback controllers improves treatment safety.
Duration of biological effect
1 hr
Safety-related matter
The paper notes that integration of a real-time acoustic feedback controller has improved treatment safety during focused ultrasound-mediated BBB opening; no specific adverse effects are reported.
Brain Region
Ultrasound Parameters
Ultrasound instrument
not provided
FUS Frequency
0.2-1.5 MHz and MHz
FUS Intensity
Not provided
FUS Pressure
not provided
FUS Mode
Not provided
Pulse duration
100ms
Duration of a single FUS session
not provided
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency
not provided
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