Active targeting of nanoparticles to the brain for treating Parkinson’s disease

Parkinson`s disease is a progressive, debilitating degenerative nervous system disorder that affects patients globally. The disease mainly affects dopaminergic neurons, through the aggregation of alpha-synuclein (AS) inside and outside the neuronal body, which results in degrading the neurons. Aggregated AS binds the proteasome, inhibits cell activity and results in an interruption to dopaminergic neurotransmission.

In parallel, nanotechnology is an innovative medical tool with promise for treating neurodegenerative diseases.

One of the main obstacles in treating neurodegenerative diseases of the brain is the low biodistribution of the nanoparticles to the brain.

Our research goal is to develop targeted liposomes to the brain for treating Parkinson`s disease. By chemical tools, we conjugated and screened different targeting moieties to the surface of the nanoparticles. We found that the chemical identity of the targeting moiety plays an important role in the ability of nanoparticles to cross the blood-brain barrier (BBB) and be taken up by neurons. In Parkinson’s disease, unique receptors are overexpressed along with the BBB, and we found that targeted nanoparticles accumulate in the brain neurons at increased rates. In addition, when loading the particles with therapeutic monoclonal antibodies (mAbs), which bind to early AS oligomer fibrils, AS aggregation was inhibited.
In conclusion, this study assessed the ability to increase the penetration of liposomes loaded with therapeutic monoclonal antibodies into the brain during Parkinson`s disease. We found that active targeting improved brain uptake and that the identity of the targeting moiety plays a significant role in the crossing of the brain and neuronal uptake.