Millimeter-precision drug delivery to the brain

Date:
October 5, 2020
Source:
ETH Zurich
Summary:
Focused ultrasound waves help researchers to deliver drugs to
the brain with pinpoint accuracy, in other words only to where
their effect is desired. This method is set to enable treatment
of psychiatric and neurological disorders and tumours with fewer
side effects in the future.



FULL STORY ========================================================================== Researchers at ETH Zurich have developed a method for concentrating
and releasing drugs in the brain with pinpoint accuracy. This could
make it possible in the future to deliver psychiatric and cancer drugs
and other medications only to those regions of the brain where this is medically desirable.


========================================================================== Today, this is practically impossible -- drugs travelling through the bloodstream reach the entire brain and body, which in some cases causes
side effects. The new method is non-invasive, with precise drug delivery
in the brain controlled from outside the head using ultrasound. Mehmet
Fatih Yanik, Professor of Neurotechnology, and his team of scientists
have published their findings in the journal Nature Communications.

In order to prevent a drug from acting on the entire brain and body,
the new method involves special drug carriers that wrap the drugs in
spherical lipid vesicles attached to gas-containing ultrasound-?sensitive microbubbles. These are injected into the bloodstream, which transports
them to the brain. Next, the scientists use focused ultrasound waves in a two-?stage process. Focused ultrasound is already employed in oncology to destroy cancer tissue at precisely defined points in the body. In the new invention, however, the scientists work with much lower energy levels,
which do not damage the tissue.

Trapping drugs with sound waves In the first step, the scientists use
low energy ultrasound waves to cause the drug carriers to aggregate at
the desired site within the brain. "What we're doing is using pulses of ultrasound essentially to create a virtual cage from sound waves around
the desired site. As the blood circulates, it flushes the drug carriers
through the whole brain. But the ones that enter the cage can't get back
out," Yanik explains.

In the second step, the researchers use a higher level of ultrasound
energy to get the drug carriers to vibrate at this site. Shear forces
destroy the lipid membranes around the drugs, releasing the drugs to be absorbed by the nerve tissue present at the site.

The researchers have demonstrated the effectiveness of the new method in experiments on rats. First they encapsulated a neuro-?inhibitory drug
in the drug carriers. Then, using the new technique, they successfully
blocked a specific neural network connecting two areas of the brain. The scientists were able to show in the experiments that only this one
particular part of the neuronal network was blocked and that the drug
did not act on the entire brain.

More efficient drug delivery "Because our method aggregates drugs at the
site in the brain where their effect is desired, we don't need nearly as
high a dose," Yanik says. In their experiments on rats, for instance,
the quantity of drug that they used was 1,300 times smaller than the
typical dose needed.

Other research groups have already tried to use focused ultrasound to
enhance delivery of drugs to specific regions of the brain. However,
these approaches couldn't trap and concentrate drugs locally, and they
instead relied on causing local damage to the blood vessel cells in
order to increase the drug transport from the blood to the nerve tissue
with potentially long-?term detrimental consequences. "In our approach,
the physiological barrier between the bloodstream and nervous tissue
remains intact," Yanik says.

The scientists are currently testing the effectiveness of their method
in animal models of mental illness, for example to reduce anxiety,
of neurological disorders and to target lethal brain tumours that are surgically inaccessible.

Once its effectiveness and advantages have been confirmed in animals will researchers be able to advance application of the method to alleviate
suffering in humans.

This project was funded under the European Union's Horizon 2020 research
and innovation program.


========================================================================== Story Source: Materials provided by ETH_Zurich. Original written by
Fabio Bergamin. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Mehmet S. Ozdas, Aagam S. Shah, Paul M. Johnson, Nisheet Patel,
Markus
Marks, Tansel Baran Yasar, Urs Stalder, Laurent Bigler, Wolfger von
der Behrens, Shashank R. Sirsi, Mehmet Fatih Yanik. Non-invasive
molecularly- specific millimeter-resolution manipulation of
brain circuits by ultrasound-mediated aggregation and uncaging
of drug carriers. Nature Communications, 2020; 11 (1) DOI:
10.1038/s41467-020-18059-7 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201005101529.htm

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