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The First Step into the Brain: Uptake of NIO‐PBCA Nanoparticles by Endothelial Cells in vitro and in vivo, and Direct Evidence for their Blood–Brain Barrier Permeation
Author(s) -
Weiss Clemens K.,
Kohnle MariaVerena,
Landfester Katharina,
Hauk Thomas,
Fischer Dietmar,
SchmitzWienke Julia,
Mailänder Volker
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200800130
Subject(s) - transcytosis , in vivo , blood–brain barrier , biophysics , in vitro , chemistry , internalization , permeation , nanoparticle , retina , microbiology and biotechnology , biochemistry , biology , membrane , materials science , endocytosis , nanotechnology , central nervous system , endocrinology , receptor , neuroscience
By using fluorescent polysorbate 80 coated poly( n‐ butylcyanoacrylate) (PBCA) nanoparticles in an in vivo study, direct evidence was found for the presence of nanoparticles entering the brain and retina of rats. The nanoparticles, prepared with a miniemulsion process, were labeled in situ with a fluorescent dye and coated with polysorbate 80. After preparation the particle size, ζ potential, and the molecular weight distribution were determined. BMEC cells were used as an in vitro model for the BBB. The cells showed significant uptake of the particles, but no transcytosis could be observed in vitro. After applying the particles to the animals at two concentrations, cryosections of the brains and retinas were prepared. Regarding the sections of the rats that received the lower dose, co‐localization of the applied fluorescent particles and the stained endothelial cells could be detected in the brain and retina, indicating particle internalization in the endothelial cells. Applied at higher doses, the particles could be detected within the brain and retina with few co‐localized signals, suggesting passage through the blood–brain and blood–retina barriers.