Good vibrations: ETH Zurich scientists tap ultrasound for targeted drug delivery to the brain

A team of Swiss scientists is pitching a novel method to deliver drugs to specific regions of the brain, and they’re not relying on the usual nanoparticles to do it. Instead, the team is taking a sonic approach.

Researchers at ETH Zurich say they’ve developed a new method for concentrating and releasing drugs in the brain using ultrasound. The noninvasive, targeted delivery system uses a lipid carrier. When the drug-carrier combo reaches the right spot, the team hits it with a salvo of ultrasound waves. This both locks the carrier in place and allows the researchers to control the drug's release.

The approach could be used to deliver treatments for mental illness, neurological disorders and cancer, all with fewer side effects, the team said in a release.

The research is still early-stage stuff; the ultrasound technique recently passed muster in a rat study published in the journal Nature Communications. If it moves into and beyond the clinic, it could lower the amount of medication needed to treat those diseases and enable targeting of surgically-inaccessible brain tumors, lead study author and professor of neurotechnology at ETH Zurich, Mehmet Fatih Yanik, said.

To start, the team encases drugs—in the case of the rat trial, the neuro-inhibitor muscimol, though the team says their system should work with other FDA-approved neurological and neuropsychiatric drugs—in spherical lipid vesicles attached to gas-filled, ultrasound-sensitive microbubbles. The lipid carriers are then injected into the bloodstream, which carries them to the brain.

Next, the team conducts a two-step ultrasound rhythm—a so-called "aggregating-uncaging" sequence.

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The first phase relies on low-energy ultrasound waves, which cause the drug carriers to gather at a specific site in the brain.

“What we’re doing is using pulses of ultrasound essentially to create a virtual cage from sound waves around the desired site,” Yanik said in a release. “As the blood circulates, it flushes drug carriers through the whole brain. But the ones that enter the cage can’t get back out.”

Next, the team cranks the volume, pitting a higher level of ultrasound energy against the drug carriers, which causes them to vibrate. Sheer force destroys the lipid membranes, releasing the drugs for absorption.

Prior attempts at ultrasound-directed drug delivery have come up short, failing to trap and concentrate drugs locally. Instead, many of these approaches have looked to intentionally inflict local damage to blood vessels to increase drug transport from the blood to nerve tissue—a risky move that can have serious long-term side effects. Plus, it wouldn't be workable for the lifelong drug treatment needed to tackle many brain disorders, Yanik said. 

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The ETH team, on the other hand, envisions their carrier-ultrasound combo working with approved neurological and neuropsychiatric drugs already able to cross the blood-brain barrier. By concentrating and controlling the release of those meds at a particular site, they say they're able to deliver small molecules "with millimeter precision without opening" that barrier.

Yanik’s team successfully encased and delivered drugs using the lipid-ultrasound system in their rat trial, managing to block a specific neural network connecting two areas of the brain. The team was then able to show that drugs marshaled into the sound wave cages only acted on that particular site.

As for next steps, the ETH researchers already have a slew of preclinical trials in the hopper, testing their method in animal models of mental illness, such as anxiety, and neurological disorders. They’re also pitting their sonic delivery method against brain tumors that cannot be removed via surgery.