In the new study, the researchers took a cue from previous use of nanoparticles and ultrasound to deliver chemotherapeutic drugs to tumors under the skin. In their latest experiments, Green’s group designed nanoparticles with an outer expandable “cage” made of a biodegradable plastic, whose molecular building blocks are oil-loving at one end and water-loving at the other. The oil-loving ends cling together and form an expandable sphere with the water-loving ends on the outside. The oil-loving ends bind the drug to be delivered, which in this case was propofol, an anesthetic commonly used to treat seizures in people.

The center of the cage was filled with the liquid perfluoropentane. When the sound waves of ultrasound — delivered noninvasively across the scalp and skull with FDA-approved devices — strike perfluoropentane in the center of the nanoparticles, the liquid transforms to a gas, expanding the surrounding cage and letting the propofol escape.


Before testing their idea on animals, Green and his colleagues fine-tuned their ultrasound protocol by testing nanoparticles in plastic tubes, seeking to pinpoint pulses of the right power and frequency to release adequate amounts of the drug without being strong enough to damage the BBB, a known effect of high-powered ultrasound.

They also tested the distribution of the nanoparticles in rats by adding a fluorescent dye to the particles and measuring the amount of dye found in blood and organ samples over time. The majority of the particles ended up in the spleen and liver, which are important housekeeping organs in the body. As expected, particles were not found in the brain because they are too big to pass through the BBB. Instead, the researchers were relying on propofol’s own ability to pass through the BBB once released locally from the nanoparticles.

To see whether their method could provide medical relief to live animals, they then gave rats a drug that causes seizures, followed by the propofol-laden nanoparticles. They used MRI to guide their application of the ultrasound to the rat brain and thus release the drug from nanoparticles floating through infiltrating blood vessels. As soon as they applied the ultrasound, the seizure activity of the rats calmed down.

“These experiments show the effectiveness of this method to manipulate the function of brain cells through the precise delivery of drugs,” says Green. “In humans, ultrasound machines can target a volume as small as a few millimeters cubed, less than one ten-thousandth of the brain.”

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