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Transport of PEGylated-PLA nanoparticles across a blood brain barrier model, entry into neuronal cells and in vivo brain bioavailability

Rabanel, Jean-Michel, Piec, Pierre-Alexandre, Landri, Sarra, Patten, Shunmoogum A. et Ramassamy, Charles ORCID: https://orcid.org/0000-0002-3252-5878 (2020). Transport of PEGylated-PLA nanoparticles across a blood brain barrier model, entry into neuronal cells and in vivo brain bioavailability Journal of Controlled Release , vol. 328 . p. 679-695. DOI: 10.1016/j.jconrel.2020.09.042.

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Résumé

Treatments of neurodegenerative diseases (NDDs) are severely hampered by the presence of the blood-brain barrier (BBB) precluding efficient brain drug delivery. The development of drug nanocarriers aims at increasing the brain therapeutic index would represent a real progress in brain disease management. PEGylated polyester nanoparticles (NPs) are intensively tested in clinical trials for improved drug delivery. Our working hypothesis was that some surface parameters and size of NPs could favor their penetration across the BBB and their neuronal uptake. Polymeric material PEG-b-PLA diblocks were synthesized by ring opening polymerisation (ROP) with PEG(2000) or PEG(5000). A library of polymeric PEG-b-PLA diblocks NPs with different physicochemical properties was produced. The toxicity, endocytosis and transcytosis through the brain microvascular endothelial cells were monitored as well as the neuronal cells uptake. In vitro results lead to the identification of favourable surface parameters for the NPs endocytosis into vascular endothelial cells. NPs endocytosis took place mainly by macropinocytosis while transcytosis was partially controlled by their surface chemistry and size. In vivo assays on a zebrafish model showed that the kinetic of NPs in circulation is dependent on PEG coating properties. In vivo findings also showed a low but similar translocation of PEG-b-PLA diblocks NPs to the CNS, regardless of their properties. In conclusion, modulation of surface PEG chain length and NPs size impact the endocytosis rate of NPs but have little influence on cell barriers translocation; while in vivo biodistribution is influenced by surface PEG chain density.

Type de document: Article
Mots-clés libres: Blood brain barrier; Diblock polymer; Endocytosis inhibition; N2a; Nanoparticles; PEG-b-PLA; SK-N-SH; Transcytosis; Zebrafish; bEnd.3
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 20 juill. 2021 04:09
Dernière modification: 15 févr. 2022 21:25
URI: https://espace.inrs.ca/id/eprint/11670

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