Concentrates and releases drugs in the brain with pinpoint accuracy

Scientists at ETH Zurich say they have developed a technique to concentrate and release the drug into the brain very accurately. According to the team, this may in the future allow psychiatric and cancer medications and other medications to be delivered only to areas of the brain where it is medically desirable.

Today, researchers add that this is virtually impossible. Drugs that travel through the bloodstream reach the brain and the entire body, causing side effects in some cases. The new method is non-invasive and drug delivery in the brain is controlled from outside the head using ultrasound.

Dr. Mehmet Fatih Yanik, a professor of neurotechnology, and his group have published their findings.Non-invasive molecule-specific millimeter-resolution manipulation of brain circuits by ultrasound-mediated aggregation and drug carrier uncaging, “In the journal Nature Communications..

“Non-invasive, molecule-specific focal modulation of brain circuits with low off-target effects can lead to breakthroughs in the treatment of brain disorders. Systematic infusion of designed ultrasound-controlled drug carriers. Then, we apply a new two-component aggregation and uncaging focused ultrasound sequence (AU-FUS) to the target in the brain, “the researchers write.

“The first sequence aggregates drug carriers with millimeter accuracy. The second sequence localizes carrier cargo to achieve high target specificity without compromising the blood-brain barrier (BBB). When released from the carrier, the drug passes through a locally intact BBB. By locally concentrating and releasing GABA, a circuit-specific manipulation of sensory signals in the rat motor cortex. Shows_A Receptor agonist from ultrasound controlled carriers. “

“Our approach uses orders of magnitude (1300 times) less drug than required for systemic injections and requires very low ultrasound pressure (20 minutes of the FDA safety limit for diagnostic imaging). 1). BBB uses passive cavitation detection (PCD), MRI contrast agents and, more importantly, shows that it remains intact by the extravasation of sensitive fluorescent dyes and immunohistochemistry. . “

To prevent the drug from acting on the brain and the entire body, the new method uses a special drug carrier that wraps the drug in spherical lipid vesicles attached to gas-containing ultrasound-sensitive microbubbles. These are injected into the bloodstream and carried to the brain.

Scientists then use focused ultrasound in a two-step process. Focused ultrasound has already been adopted in oncology to destroy cancerous tissue at precisely defined points in the body. But with the new invention, scientists work at much lower energy levels and do not damage tissues.

In the first step, scientists use low-energy ultrasound to aggregate the drug carrier to the desired site in the brain.

“What we’re doing is basically using ultrasonic pulses to create a virtual cage from the sound waves around the destination. When blood circulates, drug carriers flow throughout the brain. But what’s in the cage is irreversible, “explains Yannick.

In the second step, researchers use higher levels of ultrasonic energy to vibrate the drug carrier at this site. Shear force breaks down the lipid membrane around the drug and releases the drug that is absorbed by the nerve tissue present at that site.

Researchers report that experiments in rats have demonstrated the effectiveness of the new method. First, they encapsulated neuroinhibitory drugs in drug carriers. We then used a new technique to successfully block a particular neural network that connects two regions of the brain. Scientists have been able to show in experiments that only this particular part of the neural network was blocked and the drug did not affect the entire brain.

“Our method aggregates the drug in areas of the brain where its effect is desired, so we require very few high doses,” says Yanik. For example, in experiments with rats, the amount of drug used was 1,300 times less than the usual dose required.

“With our approach, the physiological barrier between blood flow and nervous tissue remains intact,” continues Yanik.

Scientists are currently testing the effectiveness of their methods in animal models of psychiatric disorders, for example to reduce anxiety and neuropathy and target deadly brain tumors that are not surgically accessible. I will. Once its effectiveness and benefits are confirmed in animals, researchers can proceed with the application of methods to reduce human distress.