January 23, 2017 -- Biomedical engineers at Johns Hopkins report they have worked out a noninvasive way to release and deliver concentrated amounts of a drug to the brain of rats in a temporary, localized manner using ultrasound. The method first “cages” a drug inside tiny, biodegradable “nanoparticles,” then activates its release through precisely targeted sound waves, such as those used to painlessly and noninvasively create images of internal organs.

Because most psychoactive drugs could be delivered this way, as well as many other types of drugs, the researchers say their method has the potential to advance many therapies and research studies inside and outside the brain.

They also say that their method should minimize a drug’s side effects because the drug’s release is concentrated in a small area of the body, so the total amount of drug administered can be much lower. And because the individual components of the technology — including the use of the specific biomaterials, ultrasound and FDA-approved drugs — have already been tested in people and found to be safe, the researchers believe their method could be brought into clinical use more quickly than usual: They hope to start the regulatory approval process within the next year or two.
“If further testing of our combination method works in humans, it will not only give us a way to direct medications to specific areas of the brain, but will also let us learn a lot more about the function of each brain area,” says Jordan Green, Ph.D., associate professor of biomedical engineering, who is also a member of the Kimmel Cancer Center and the Institute for Nanobiotechnology.

Details of the research are published on Jan. 23 in the journal Nano Letters.

The new research, Green says, was designed to further advance means of getting drugs safely to the brain, a delicate and challenging organ to treat. To protect itself from infectious agents — and from swelling that can be caused by the immune system, for example — the brain is surrounded by a molecular fence, called the blood-brain barrier (BBB), which lines the surface of every blood vessel feeding the brain. Only very small drug molecules that dissolve in oil can get through the fence, along with gases. Because of this, most drugs developed for treating brain disorders fit those criteria but are dispersed to all parts of the brain — and the rest of the body, where they may be unneeded and unwanted.

Raag Airan, M.D., Ph.D., assistant professor of radiology at Stanford University School of Medicine and co-author of the paper, says: “When working with a patient who has post-traumatic stress disorder, for example, it would be nice to quiet down the overactive part of the brain — for instance, the amygdala — during talk therapy sessions. Current technologies can at best quiet down half of the brain at a time, so they are too nonspecific to be useful in this setting.”

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