EAGER: Investigations of pulsed focused ultrasound for increasing the average pore size in brain tissue

University Of Maryland At Baltimore, Baltimore

Investigators

Abstract

CBET - 1557922 PI: Frenkel, Victor The goal of this project is to determine whether exposure of brain tissue to pulsed focused ultrasound increases the spaces between cells, which could enhance the motion of therapeutic compounds and nanoparticle drug carriers through the brain. The motion of therapeutic compounds such as proteins, small molecule drugs, antibodies, and drug carriers is usually restricted, owing to the limited space between cells and the extracellular matrix that fills this space. Therefore, a method to increase the average pore size in brain tissue, without causing cell damage, could improve drug delivery methods to treat a variety of neurological disorders. The investigators will design nanoparticles that are coated with polymers to promote their motion, and they will track the motion of the nanoparticles with and without exposure of the tissue to ultrasound. Results of the study will improve knowledge of the extracellular space in the brain and provide guidance in the design of more effective drug delivery strategies. The project will enlist high school students and undergraduates, including underrepresented students from West Baltimore City. This EAGER award will support experiments to study pulsed ultrasound exposure as a means of effectively altering the microstructure of the extracellular space with the goal of improving the dispersion of nanometer-sized therapeutic agents in the brain. Previous studies have shown that pulsed focused ultrasound increases penetration of nanoparticles, antibodies, and proteins in a variety of tissue types. This project will extend these studies to brain tissue. The average pore size will be quantified using high-resolution multiple particle tracking methods. The motion of polystyrene nanoparticles, densely coated to prevent their adhesion and ranging in diameter from 40 to 500 nanometers, will be examined in thin brain slices. Effects of the ultrasound on tissue microstructure will be evaluated using transmission electron microscopy and tissue histology. Results of the project will be useful for improving interstitial drug delivery to the brain by methods such as convection-enhanced delivery.