Evaluation of effect of charge and lipid coating on ability of 60-nm nanoparticles to cross an in vitro model of the blood-brain barrier.
A cell culture model of the blood-brain barrier (BBB) consisting of a coculture of bovine brain capillary endothelial cells and rat astrocytes has been used to examine the ability of 60-nm nanoparticles with different physicochemical characteristics to cross the BBB. Neutral, anionic, and cationic nanoparticles were made from crosslinked malto-dextrins derivatized or not (neutral) with phosphates (anionic), quaternary ammoniums (cationic) ligands. Then, these particles were coated or not with a lipid bilayer made of dipalmitoyl phosphatidyl choline and cholesterol. Lipid coating of ionically charged nanoparticles was able to increase BBB crossing 3- or 4-fold compared with uncoated particles, whereas coating of neutral particles did not significantly alter their permeation characteristics across the endothelial cell monolayer. Lipid-coated nanoparticles were nontoxic toward BBB integrity, and crossed the BBB by transcytosis without any degradation. Furthermore, a 27-fold increase in albumin transport was observed when albumin had previously been loaded in the cationic lipid-coated nanoparticles. The influence of red blood cells was studied; a marked inhibition of the transport was observed, probably due to strong interaction between nanoparticles and red blood cells.
Fenart
L
L
Unité mixte Institut Pasteur de Lille-Université d'Artois, Faculté des sciences Jean-Perrin, Lens, France.
Casanova
A
A
Dehouck
B
B
Duhem
C
C
Slupek
S
S
Cecchelli
R
R
Betbeder
D
D
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D018920:Coculture Techniques; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D008081:Liposomes; D008856:Microscopy, Fluorescence; D008863:Microspheres; D010743:Phospholipids / Q000378:metabolism; D011134:Polysaccharides; D051381:Rats
D008081:Liposomes; D010743:Phospholipids; D011134:Polysaccharides