The treatment of diseases like Alzheimer’s or Parkinson’s is difficult as drugs should be able to penetrate the blood-brain barrier. Thus, the administered doses must be high, with only a small fraction reaching the brain. This can cause major systemic side effects.
Professor Charles Ramassamy and postdoctoral researcher Jean-Michel Rabanel analyzing nanoparticles on the Nanosight NS 300. Image Credit: Institut national de la recherche scientifique.
Postdoctoral researcher Jean-Michel Rabanel, led by Professor Charles Ramassamy from the Institut national de la recherche scientifique (INRS) seeks to overcome this problem by improving polymer-coated nanoparticles to enhance their permeability across the barrier and thus deliver encapsulated drugs in the brain.
As part of a new study, the researchers showed the effectiveness of a particular polymer with zwitterion properties. In general, these molecules are neutral and feature an equal number of positive and negative charges to simulate the molecules on the surface of cells.
The team compared the properties of two different polymer coatings on polylactic acid (PLA) nanoparticles — biocompatible materials that can be easily eliminated by the human body.
Promising Coatings
The first coating was made of polyethylene glycol (PEG) and had already been tested on zebrafish. The transparent body of zebrafish enables researchers to observe the nanoparticle distribution in almost real-time. The second coating was made of zwitterionic polymer and was compared under similar conditions.
With this type of experiment, we demonstrated that the zwitterionic polymer, which in theory is more biocompatible since it’s similar to molecules at the cell’s surface, have a better access to the brain. However, it is more rapidly absorbed by blood vessel walls, which reduces their circulation time.
Charles Ramassamy, Professor, Institut national de la recherche scientifique
PEG is thus still the most promising coating polymer in the case of the bloodstream. By contrast, the zwitterionic polymer could possibly lead to weaker immune system response. According to Professor Ramassamy, a mixture of both polymers could help tap the advantages of each.
Our findings demonstrate that the drug coating is a very important factor in the therapeutic use of nanoparticles. It’s an interesting avenue for delivering drugs directly to the brain and improving the treatment for neurodegenerative diseases.
Charles Ramassamy, Professor, Institut national de la recherche scientifique
Professor Ramassamy is also the holder of the Louise and André Charron Research Chair on Alzheimer’s Disease at the Armand-Frappier Foundation.
Société Alzheimer de Québec reports that at present, neurodegenerative diseases affect over 565,000 Canadians, including 152,121 in Québec.
Journal Reference:
Rabanel, J.-M., et al. (2021) Nanoparticle shell structural cues drive in vitro transport properties, tissue distribution and brain accessibility in zebrafish. Biomaterials. doi.org/10.1016/j.biomaterials.2021.121085.