10 May 2024

Nanoparticles helped deliver a drug directly to the brain

Nanoparticles could be used to deliver drugs to the brain and thereby help patients with neurodegenerative diseases.

The treatment of neurodegenerative diseases - slowly progressive, inherited or acquired ailments of the nervous system, the best known of which are Alzheimer's and Parkinson's diseases, as well as dementia - is severely hampered by the blood-brain barrier between the circulatory system and the central nervous system, preventing effective drug delivery to the brain. 

And the development of drug nanocarriers aimed at increasing the brain's therapeutic index (the ratio between toxic and effective doses of a drug that cause the appearance of a half-maximal effect) could bring real progress in the treatment of such age-related diseases. Thus, laboratories are testing pegylated polyester nanoparticles to improve drug delivery. 

It is devoted to this work of scientists from the National Institute for Scientific Research (Canada), whose working hypothesis was that some surface parameters and size of nanoparticles can help to overcome the blood-brain barrier and their capture by neurons. The study is published in the Journal of Controlled Release.

"The blood-brain barrier filters out harmful substances to prevent them from entering the brain unimpeded. But that same barrier blocks the passage of drugs," pharmacologist Charles Ramassami told the Journal of Controlled Release. - Normally, high doses are required to deliver small amounts of a drug to the brain. What remains in the bloodstream provokes serious side effects. Often this discomfort causes the patient to discontinue treatment. The use of nanoparticles that encapsulate drugs will result in fewer side effects and improved brain function. <...> We have created particles made of polylactic acid, a biocompatible material that is easily excreted by the body. A layer of polyethylene glycol coats these nanoparticles and makes them 'invisible' to the immune system so they can circulate in the body through the bloodstream for longer."

To confirm the effectiveness of this method, the scientists first tested it on cultured cells and then on a popular model organism, danio fish, which were grown in a medium with these nanoparticles. "Danio fish have several advantages. Their blood-brain barrier is similar to that of humans, and the transparent skin of these fish allows us to see the distribution of nanoparticles in almost real time," Ramassami noted.

Thus, in vivo ("inside the cell") scientists were able to observe the overcoming of the blood-brain barrier - it happened just four to five hours after the nanoparticles entered the bloodstream of fish. In addition, experiments on human cultured cells confirmed the lack of toxicity of selected nanoparticles. The authors of the study plan to continue laboratory tests on other animal models and in the future to treat patients suffering from neurodegenerative diseases in this way.

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