Ultrasound for drug and gene delivery to the brain.
Authors: Hynynen K
Noninvasive, transient, and local image-guided blood-brain barrier disruption (BBBD) has been demonstrated with focused ultrasound exposure in animal models. Most studies have combined low pressure amplitude and low time average acoustic power burst sonications with intravascular injection of pre-formed micro-bubbles to produce BBBD without damage to the neurons. The BBB has been shown to be healed within a few hours after the exposure. The combination of focused ultrasound beams with MR image guidance allows precise anatomical targeting as demonstrated by the delivery of several marker molecules in different animal models. This method may in the future have a significant impact on the diagnosis and treatment of central nervous system (CNS) disorders. Most notably, the delivery of the chemotherapy agents (liposomal Doxorubicin and Herceptin) has been shown in a rat model.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
Demonstrate that MR-guided focused ultrasound combined with intravenously administered microbubbles can noninvasively, transiently, and locally disrupt the blood–brain barrier to enable targeted delivery of therapeutic agents without neuronal damage.
Animal model / Human subject
Rat; strain None; age None; sex None
MRI or image guidance method
MR image guidance
Cargo name and characteristics
Liposomal Doxorubicin (liposome-formulated small-molecule chemotherapeutic nanoparticle) and Herceptin (trastuzumab, monoclonal antibody protein)
Outcomes and Safety
Summary of Outcomes
Focused ultrasound combined with intravenous pre-formed microbubbles produced transient, localized, noninvasive blood–brain barrier disruption that enabled delivery of marker molecules and chemotherapies (liposomal Doxorubicin, Herceptin) in animal models without neuronal damage and with the BBB healing within a few hours. Successful parameters included low pressure amplitude, low time-average acoustic power burst sonications, use of pre-formed microbubbles, and MR image guidance.
Safety-related matter
Most studies produced BBBD without damage to the neurons. The BBB was shown to be healed within a few hours after the exposure.
Brain Region
Ultrasound Parameters
FUS Mode
pulsed
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
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