Nanoparticles Show Potential as Transport Agents for Parkinson’s Treatments
Nanoparticles as transport agents have a potential to more effectively deliver medications to the brain, opening neurological disorders such as Parkinson’s disease to new treatments, a study suggested.
But work is needed to further refine these particles, assuring their safety as well as their efficacy, its researchers wrote.
The study, “Transport of PEGylated-PLA nanoparticles across a blood brain barrier model, entry into neuronal cells and in vivo brain bioavailability,” was published in the Journal of Controlled Release.
Humans and other animals have evolved mechanisms to keep the brain, because of its importance, safe from potential harm. One of the most obvious examples is the blood-brain barrier (BBB): as its name suggests, this barrier regulates what substances in the blood are able to pass into brain tissue.
“The blood-brain barrier filters out harmful substances to prevent them from freely reaching the brain,” Charles Ramassamy, a professor at Institut National de la Recherche Scientifique (INRS) and study co-author, said in a press release.
“But this same barrier also blocks the passage of drugs,” Ramassay added.
Medications to treat neurological diseases almost invariably need to get into the brain to be of any benefit. Because of the BBB, however, doses often have to be extremely high to allow even a small amount of a medication to reach the brain — and higher doses usually mean stronger side effects.
One approach being tested to improve the delivery of medications able to cross into the brain is nanoparticles. Conceptually, this involves coating a medication with molecules that can cross the barrier, so that the treatment essentially rides into the brain via its coating.
“Drug delivery to the CNS [central nervous system, brain and spinal cord] mediated by NPs [nanoparticles] could represent a major breakthrough,” the researchers wrote. “However, conflicting results have been reported so far, regarding effective NPs transport across the BBB and their brain availability.”
In this study, INRS researchers describe designing nanoparticles that might more effectively cross the BBB to better target the delivery of treatments.
“We made the particles with polylactic acid (PLA), a biocompatible material that is easily eliminated by the body. A layer of polyethylene glycol (PEG) covers these nanoparticles and makes them invisible to the immune system, so they can longer circulate in the bloodstream,” Ramassamy said.
By testing multiple nanoparticles, the researchers zeroed in on molecular features best suited to crossing the BBB. For example, they found that smaller particles were generally able to cross the barrier more easily than larger particles, and differences in their PEG coating also affected this ability.
In lab tests in cell models, the team’s nanoparticles were seen to cross the BBB and to get into brain nerve cells, or neurons. The team also showed evidence that the particles could cross the BBB in living animals, specifically the zebrafish.
“This species offers several advantages. Its blood-brain barrier is similar to that of humans and its transparent skin makes it possible to see nanoparticles’ distribution almost in real time,” Ramassay said.
Importantly, in both cultured cells and zebrafish, the nanoparticles did not show any evidence of toxicity, supporting the idea that these particles can safely and effectively deliver medications to the brain. However, more research will be needed before they might be tested in patients.
“Further development of brain nanomedicine will need to confirm these findings in mammal models,” the researchers concluded.