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Sclerosis, Parkinson's disease, Alzheimer's disease and epilepsy are just some diseases of the central nervous system
The blood-brain barrier is a boundary wall between the blood and the brain, allowing only certain molecules to enter the brain
Now, in a live study that includes awake mice, a team of researchers from the University of Copenhagen has a direct insight into how to trick the impermeable wall of the blood-brain barrier to allow the drug to be delivered to the brain
They studied the so-called nanoparticle liposome drug carrier and sent it into the blood-brain barrier, while tracking and monitoring it throughout the system
"Before this study, the researchers did not understand what happened in the blood-brain barrier of the living brain, and why some nanoparticles can traverse while others cannot
With the help of colleagues from the Technical University of Denmark and Aalborg University, the researchers used two-photon imaging to deconstruct the blood-brain barrier in order to understand how nano-drug carriers pass through the blood-brain barrier in living organisms
"We monitored every step of the nanoparticle entering the brain, providing valuable knowledge for future drug design
The study, published in the journal Nature Communications, showed that brain-targeted nanoparticles are received by endothelial cells in blood vessels and venules, and endothelial cells are cells in the blood-brain barrier that are responsible for permitting or denying Molecules enter our brain tissue
Similar to the mythical Trojan horses, they are recognized by endothelial cells and transported to the brain through the blood-brain barrier
Researchers use the two-photon imaging method to study nanoparticles, which allows them to open the "black box" of the blood-brain barrier and obtain a complete picture of the nanoparticle's path through the blood-brain barrier
Now they can observe how nanoparticles circulate in the blood, how they are associated with endothelial cells over time, how many nanoparticles are absorbed by endothelial cells, how many are left behind by endothelial cells, and they enter the blood-brain barrier What happens later, and where do the nanoparticles enter the brain
Krzysztof Kucharz said: "Although the anatomy and function of the endothelium of different blood vessel types are different, this main feature of the brain has so far been overlooked in drug delivery research.
They showed that nanoparticles can enter the brain mainly in large blood vessels, namely small veins, which are surrounded by the so-called perivascular space, rather than small and numerous capillaries as previously thought
"Our results challenge the hypothesis that capillaries are the main place for nanoparticle delivery to the brain
The methodology platform developed by the author may constitute a good platform to fine-tune the nanoparticle formulation to increase transport to the brain and provide valuable information for the design of new drug delivery systems in the future
Post-capillary venules are the key locus for transcytosis-mediated brain delivery of therapeutic nanoparticles
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