Characterization of endocytosis of transferrin-coated PLGA nanoparticles by the blood-brain barrier.
Many studies showed that transferrin increases brain delivery of nanoparticles (NPs) in vivo, however the mechanisms implied in their brain uptake are not yet clearly elucidated. In this study we evaluated the endocytosis of PLGA NPs coated with transferrin on an in vitro model of the blood-brain barrier (BBB) made of a co-culture of brain endothelial cells and astrocytes. PLGA NPs were prepared using DiI as a fluorescent marker and coated with Tween 20, BSA and transferrin (Tf). Blank and BSA-NPs served as controls. The cellular toxicity on BBB of the different samples was evaluated following tight junction aperture and due to high toxicity NPs prepared with Tween 20 were discarded. The size of the NPs prepared by the solvent diffusion method, varied from 63 to 90 nm depending on DiI incorporation and surface coating. Proteins adsorption on the surface of the NPs was found to be stable for at least 12 days at 37 degrees C. Contrary to Blank or BSA-NPs, Tf-NPs were found to be highly adsorbed by the cells and endocytosed using an energy-dependent process. Studies in presence of inhibitors suggest that Tf-NPs interact with the cells in a specific manner and enter the cells via the caveolae pathway.
EA 2689, Laboratory of Physiology, IMPRT, University of Lille 2, Faculté de Médecine, pôle recherche, 1 place de Verdun, 59045 Lille, France.
Jiang
J
Chang
Youssef
Y
Jallouli
Maya
M
Kroubi
Xu-bo
XB
Yuan
Wei
W
Feng
Chun-sheng
CS
Kang
Pei-yu
PY
Pu
Didier
D
Betbeder
D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism*
D014168:Transferrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid