The results of this work are summarized in a scientific paper published this week in the prestigious Journal of Controlled Release.
In this article, the experts explain that shortly after its administration in mice, the nanoparticles coated with this antibody managed to reach the brain by crossing the blood-brain barrier (BBB), which separates the bloodstream from this tissue and is characterized by having a highly selective permeability.
The BBB works effectively by protecting the brain from pathogens and toxic substances circulating in the blood, which makes diseases affecting the brain difficult to treat, since 98% of drugs cannot cross it. Instead, natural substances like nutrients, hormones and cells of the immune system can cross this barrier and enter the brain from the blood flow.
The strategy designed by Professor Muro’s group to overcome this barrier is based precisely on the use of ICAM-1, which is one of the targets used by cells of the immune system to cross this barrier.
According to researchers at IBEC and at the University of Maryland, this is a very significant finding, since it could help optimize the release of drugs through the endothelium, which is the tissue that lines the inside of blood vessels. In this way, the drugs could effectively penetrate the blood-brain barrier and enter the brain.
“We have demonstrated how this strategy helps to transport to the brain drugs that cannot pass by itself to this organ, which could offer a new treatment for diseases such as Niemann-Pick disease type A, a congenital neurodegenerative disorder that is incurable nowadays, exposes Silvia Muro, the main author of the work.
In this sense, the expert adds that “following the same strategy, the system could adapt to release other drugs and help patients with other diseases that affect the brain, such as Alzheimer’s, Parkinson’s, meningitis or glioblastoma”. In fact, the researcher is involved in another IBEC project whose objective is to obtain new antibodies to advance this strategy towards the clinic.
Professor Silvia Muro joined IBEC in late 2017 to lead the group ‘Targeted Therapeutics and Nanodevices’, which investigates how to design nanotransporters loaded with drugs that can use the natural transport routes in the body to treat neurodegenerative, cardiovascular, and metabolic diseases or cancer.
Reference article: Rachel L.Manthe, Maximilian Loeck, Tridib Bhowmick, Melani Solomon, Silvia Muro. «Intertwined mechanisms define transport of anti-ICAM nanocarriers across the endothelium and brain delivery of a therapeutic enzyme». Journal of Controlled Release, August 2020. DOI: https://doi.org/10.1016/j.jconrel.2020.05.009