BBB is not a barrier
Nanoparticles helped deliver the drug directly to the brain
Maria Azarova, Naked Science
The injected nanoparticles moved through the bloodstream and concentrated around the vessels of the brain. Drawings from the article Rabanel et al.
The treatment of neurodegenerative diseases – slowly progressing, hereditary or acquired ailments of the nervous system, the most famous of which are Alzheimer's and Parkinson's diseases, as well as dementia – is strongly hindered by the presence of a blood-brain barrier between the circulatory system and the central nervous system, preventing the effective delivery of drugs to the brain.
And the development of drug nanocarriers aimed at increasing the therapeutic index of the brain (the ratio between toxic and effective doses of drugs that cause the appearance of a semi-maximal effect) can bring real progress in the treatment of such age-related diseases. So, in laboratories, nanoparticles of pegylated polyester are being tested to improve drug delivery.
This is the subject of a new work by scientists from the National Institute of Scientific Research (Canada), whose working hypothesis was that some surface parameters and the size of nanoparticles can help overcome the blood-brain barrier and their capture by neurons. The study was published in the Journal of Controlled Release (Rabanel et al., Transport of PEGylated-PLA nanoparticles across a blood brain barrier model, entry into neuronal cells and in vivo brain bioavailability).
Nanoparticles move through the blood-brain barrier in vitro and in vivo. The bio-distribution of particles in vivo depends on the surface density of the polyethylene glycol chain.
"The blood-brain barrier filters out harmful substances to prevent their unhindered entry into the brain. But the same barrier blocks the passage of drugs, – said pharmacologist Charles Ramassamy. – Usually, high doses are required to deliver a small amount of the drug to the brain. What remains in the bloodstream provokes serious side effects. Often this discomfort causes the patient to stop treatment. The use of nanoparticles that encapsulate drugs will lead to fewer side effects and increase the efficiency of the brain. <...> We have created particles from polylactic acid, a biocompatible material that is easily excreted by the body. A layer of polyethylene glycol covers these nanoparticles and makes them "invisible" to the immune system so that they can circulate in the body through the bloodstream for longer."
To confirm the effectiveness of this method, scientists first tested it on cultured cells, and then on a popular model organism – danio fish, which were grown in an environment with such nanoparticles. "Danios have several advantages. Their blood–brain barrier is similar to that of humans, and the transparent skin of these fish allows you to see the distribution of nanoparticles in almost real time," Ramassami said.
Thus, in vivo ("inside a living organism"), scientists were able to observe the overcoming of the blood–brain barrier - this happened just four to five hours after the nanoparticles entered the bloodstream of fish. In addition, experiments on human cultured cells confirmed the absence of toxicity of the selected nanoparticles. The authors of the study plan to continue laboratory tests on other animal models and in the future treat patients suffering from neurodegenerative diseases in this way.
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