A filter-free blood-brain barrier model to quantitatively study transendothelial delivery of nanoparticles by fluorescence spectroscopy

Autor: Jan C. M. van Hest, Edwin de Jong, Loai K. E. A. Abdelmohsen, Inge S. Zuhorn, David S. Williams
Přispěvatelé: Bio-Organic Chemistry, Macromolecular and Organic Chemistry, Center for Liver, Digestive and Metabolic Diseases (CLDM)
Rok vydání: 2018
Předmět:
Polymersomes
0301 basic medicine
Cell Membrane Permeability
Polymers
Pharmaceutical Science
Nanoparticle
02 engineering and technology
Peptides/chemistry
Polymers/chemistry
Chemistry
Lipoproteins
LDL/chemistry
G23 peptide
Brain
Vascular/metabolism
021001 nanoscience & nanotechnology
Microvessels/cytology
Filter-free BBB model
Lipoproteins
LDL
medicine.anatomical_structure
Transcytosis
Blood-Brain Barrier
Paracellular transport
Nanomedicine
Nanoparticles/chemistry
Collagen
0210 nano-technology
Blood-Brain Barrier/metabolism
Collagen/chemistry
Surface Properties
Lipoproteins
Endothelial Cells/metabolism
Blood–brain barrier
Brain/blood supply
03 medical and health sciences
medicine
Animals
Humans
Fluorescent Dyes/chemistry
Endothelium
Fluorescent Dyes
Endothelial Cells
In vitro
Rats
030104 developmental biology
Microvessels
Polymersome
Biophysics
Nanoparticles
LDL/chemistry
Endothelium
Vascular
Nanocarriers
Peptides
Endothelium
Vascular/metabolism
Zdroj: Journal of Controlled Release, 289, 14-22. Elsevier
Journal of Controlled Release, 289, 14-22. Elsevier Bedrijfsinformatie b.v.
ISSN: 0168-3659
DOI: 10.1016/j.jconrel.2018.09.015
Popis: The delivery of therapeutics to the brain is greatly hampered by the blood-brain barrier (BBB). The use of nanoparticles that can cross the BBB via the process of receptor-mediated transcytosis at blood-brain barrier endothelial cells seems a promising strategy to transport therapeutics into the brain. To screen for suitable nanocarriers, and to study the process of transcytosis, a cultured polarized monolayer of brain microvascular endothelial cells on an extracellular matrix-coated porous membrane filter is widely used as an in vitro BBB model. However, due to the adhesion of numerous types of nanoparticles to the membrane filter and within the filter pores, such a model is unsuitable for the quantification of transendothelial delivery of nanoparticles. Hence, there is a pressing need for a filter-free in vitro BBB model. Ideally, the model is inexpensive and easy to use, in order to allow for its wide use in nanomedicine and biology laboratories around the world.Here, we developed a filter-free in vitro BBB model that consists of a collagen gel covered with a monolayer of brain microvascular endothelial (hCMEC/D3) cells. The paracellular leakage of differently sized dextrans and the transcellular transport of LDL were measured to demonstrate the validity of the filter-free model. Finally, the transendothelial delivery of fluorescently-labelled PEG-P(CL-g-TMC) polymersomes that were functionalized with GM1-targeting peptides was assessed by fluorescence spectroscopy measurement of the luminal, cellular, and abluminal parts of the filter-free BBB model. Our data confirm the effectiveness of the G23 peptide to mediate transport of polymersomes across the BBB and the suitability of this filter-free in vitro model for quantification of nanoparticle transcytosis.
Databáze: OpenAIRE
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