Researchers from the Institut national de la recherche Scientifique (INRS) have shown that nanoparticles can be utilised to deliver drugs across the blood brain barrier to treat neurodegenerative diseases.
Neurodegenerative diseases (NDDs) are a group of diseases that present with progressive decline of cognitive or motor-neuronal functions. Currently, curative strategies are hindered by both the lack of understanding of the root cause of these diseases and also the blood-brain barrier (BBB). The BBB poses a huge challenge to drug penetration.
One innovative strategy to combat this is the development of drug delivery systems that can carry drugs across the BBB. For example, liposomes and nanoparticles. Drug delivery to the CNS mediated by nanoparticles presents a major breakthrough in the management of NDDs. Nonetheless, researchers have reported conflicting results regarding the effectiveness and brain availability of nanoparticles. Researchers have intensively tested PEGylated polyester nanoparticles in clinical trials for improved drug delivery.
Nanoparticle-based delivery system
In this study, published in the Journal of Controlled Release, researchers investigated the differential permeability of a library of targeting-ligand free nanoparticles with controlled physicochemical properties through the BBB. The team explored the mechanisms of cellular uptake involved in BBB crossing using an in vitro model.
In vitro results revealed favourable surface parameters for nanoparticle endocytosis into vascular endothelial cells. Nanoparticle endocytosis took place mainly by macropinocytosis. In vivo assays on a zebrafish model also showed that the kinetics of nanoparticles in circulation are dependent on PEG coating properties.
These findings demonstrate that the modulation of surface PEG chain length and nanoparticle size impact the endocytosis rate of nanoparticles, but actually have little influence on cell barrier translocation. The team noted that further development of brain nanomedicine will be important to confirm these findings in mammalian models. Nonetheless, these results show great promise in overcoming challenges of the BBB and represent a step towards treating neurodegenerative diseases.
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