Pitt Shield

Remotely controlled drug release in deep brain regions of non-human primates.

Authors: Wilson MG, Webb TD, Odéen H, Kubanek J

Many areas of science and medicine would benefit from selective release of drugs in specific regions of interest. Nanoparticle drug carriers activated by focused ultrasound-remotely applied, depth-penetrating energy-may provide such selective interventions. Here, we developed stable, ultrasound-responsive nanoparticles that can be used to release drugs effectively and safely in non-human primates. The nanoparticles were used to release propofol in deep brain visual regions. The release reversibly modulated the subjects' visual choice behavior and was specific to the targeted region and to the released drug. Gadolinium-enhanced MRI imaging suggested an intact blood-brain barrier. Blood draws showed normal clinical chemistry and hematology. In summary, this study provides a safe and effective approach to release drugs on demand in selected deep brain regions at levels sufficient to modulate behavior.

Introduction

Purpose Drug delivery WITHOUT BBB opening
Study Objective Develop and test ultrasound-responsive nanoparticles for safe, targeted drug release in deep brain regions of non-human primates to modulate behavior.
Animal model / Human subject Non-human primates (species not specified; strain not specified; age not specified; sex not specified)
Disease model Healthy
Targeted brain region(s) Deep Brain Visual Regions
Cargo name and characteristics Propofol — small-molecule intravenous anesthetic/sedative released from ultrasound-responsive nanoparticles

Outcomes and Safety

Summary of Outcomes Focused ultrasound-triggered release of propofol from ultrasound-responsive nanoparticles in deep visual brain regions of non-human primates reversibly modulated visual choice behavior in a region- and drug-specific manner, without detectable blood–brain barrier disruption or systemic toxicity. The study reports successful activation using focused ultrasound to release the drug; no multiple FUS parameter sets were detailed.
Safety-related matter The study reports the nanoparticles released drugs effectively and safely in non-human primates. Gadolinium-enhanced MRI suggested an intact blood-brain barrier and blood draws showed normal clinical chemistry and hematology, indicating no adverse effects.

Brain Region

Ultrasound Parameters

Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None

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