Effects of γ- and Hydroxypropyl-γ-cyclodextrins on the Transport of Doxorubicin across an in Vitro Model of Blood-Brain Barrier

Autor: Roméo Cecchelli, Eric Monflier, Veronique Monnaert, Laurence Fenart, Didier Betbeder, Christophe Landry, Sébastien Tilloy, Anne-Marie Lenfant, Hervé Bricout
Rok vydání: 2004
Předmět:
ATP Binding Cassette Transporter
Subfamily B
Cell Membrane Permeability
Endothelial permeability
Biological Transport
Active
Fluorescent Antibody Technique
Antineoplastic Agents
Nanotechnology
Capillary endothelial cells
Blood–brain barrier
In vitro model
03 medical and health sciences
0302 clinical medicine
Piperidines
polycyclic compounds
medicine
Animals
Doxorubicin
030304 developmental biology
Pharmacology
0303 health sciences
Antibiotics
Antineoplastic
Triazines
Chemistry
Electric Conductivity
technology
industry
and agriculture
Endothelial Cells
Penetration (firestop)
Coculture Techniques
Capillaries
Rats
3. Good health
carbohydrates (lipids)
medicine.anatomical_structure
Microscopy
Fluorescence
Blood-Brain Barrier
Toxicity
Biophysics
Molecular Medicine
Neuroglia
Spectrophotometry
Ultraviolet
030217 neurology & neurosurgery
gamma-Cyclodextrins
medicine.drug
Zdroj: Journal of Pharmacology and Experimental Therapeutics. 311:1115-1120
ISSN: 1521-0103
0022-3565
DOI: 10.1124/jpet.104.071845
Popis: Association between doxorubicin (DOX) and gamma-cyclodextrin (gamma-CD) or hydroxypropyl-gamma-CD (HP-gamma-CD) has been examined to increase the delivery of this antitumoral agent to the brain. The stoichiometry and the stability constant of gamma-CD or HP-gamma-CD and DOX complexes were determined in physiological medium by UV-visible spectroscopy. By using an in vitro model of the blood-brain barrier (BBB), endothelial permeability and toxicity toward the brain capillary endothelial cells of DOX, gamma-CD, and HP-gamma-CD were performed. For each CD, endothelial permeability was relatively low and a disruption of the BBB occurred at 20 microM, 20 mM, and 50 mM DOX, gamma-CD, and HP-gamma-CD, respectively. Increasing amounts of CDs were added to a fixed DOX concentration. Addition of gamma-CD or HP-gamma-CD, up to 15 and 35 mM, respectively, decreased the DOX delivery, probably due to the low complex penetration across the BBB and the decrease in free DOX concentration. Higher CD concentrations increased the DOX delivery to the brain, but this effect is due to a loss of BBB integrity. In contrast to what was observed on Caco-2 cell model with various drugs, CDs are not able to increase the delivery of DOX across our in vitro model of BBB.
Databáze: OpenAIRE
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