Scientists break down the brain’s protective barrier to administer drugs

Source: European Commission / CORDIS

Editor: Monika Stelmach
|Date: May 12, 2022

A new technique that allows drugs to be transported across the difficult blood-brain barrier opens new possibilities for the treatment of diseases of the central nervous system.

However, protecting the brain from pathogens and toxins in the blood relies primarily on a specialized system of cells known as the blood-brain barrier. This barrier acts as a specific boundary between blood vessels and brain tissue. Its role is both to protect the brain from toxic substances present in the blood and to provide it with nutrients. It is precisely its effectiveness in preventing the entry of unwanted substances into the brain that makes it extremely difficult to treat diseases of the brain and central nervous system – the intake of medicinal substances becomes a problem.

A team of researchers supported in part by the European Union-funded V-EPC project has found a new way to temporarily open the blood-brain barrier to deliver drugs to brain tissue. Their technique uses light and nanoparticles to disrupt connections formed by closely adjacent cells in barrier capillaries, allowing drugs to cross that boundary and reach their destination.

Possible treatment methods
A team of researchers from Ireland, Italy and the United States demonstrated how the new method described in a study published in the scientific journal Nano Letters works in a mouse model. According to a press release published on ScienceDaily, one of the study’s corresponding authors, Dr. Zhenpeng Qin of the University of Texas at Dallas (UT Dallas), believes that this approach could lead to the development of treatments for tumors. brain and Lou Gehrig’s disease. It can also help you recover from a stroke and enable the use of gene therapies. However, before the new solution can be applied to humans, further research and testing is required.

“Methods of increasing blood-brain barrier permeability are critical to the development of treatments for central nervous system diseases,” says Xiaoqing Li, a doctoral student in biomedical engineering at UT Dallas and one of the co- study authors.

In the study, scientists used synthesized gold nanoparticles bound to the BV11 antibody to target cellular junctions inside the barrier. Additionally, the team used intravenously introduced adenoviruses (AAVs) used in gene therapies and then applied laser stimulation. The results show that the viruses introduced by the researchers successfully crossed the blood-brain barrier and infected 64% of right hemisphere neurons through laser excitation. This proves that transcranial picosecond laser stimulation of gold nanoparticles after intravenous administration of AAV increases the permeability of the blood-brain barrier.

Using laser pulses to activate the nanoparticles creates a slight mechanical force that temporarily breaks down the barrier, allowing the drug to enter the brain’s bloodstream, Li says. However, this action does not cause permanent damage to the barrier. protective and does not cause constriction and expansion of blood vessels.

In another study supported by the V-EPC (Inherited dysfunctions of brain microcirculation) project, researchers investigated the formation of cavernous hemangiomas in mice, clusters of abnormal blood vessels that form in the brain and spinal cord. The study led to the development of a preclinical mouse model that will lead to the development of new drugs for the treatment of acute brain and spinal cord hemorrhages caused by cavernous hemangiomas. The results of the study have been published in the journal iScience.

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