[en] Cyclodextrins have been identified as promising adjuvants for pulmonary drug delivery. However, concerns regarding possible adverse effects on the respiratory epithelium may limit their development in inhaled products. Concentrations (10-50 mM) of three ß-cyclodextrin derivatives, randomly methylated ß-cyclodextrin (RAMEB), hydroxypropyl-ß-cyclodextrin (HPßCD) and Kleptose® CRYSMEB, were applied to human respiratory epithelial (Calu-3) cell layers and effects on permeability were evaluated by 14C-mannitol permeability and transepithelial electrical resistance (TEER) measurements. Each cyclodextrin produced a concentration-dependent increase in mannitol flux which was associated with a drop in TEER. Increases in mannitol flux were the highest after exposure to RAMEB and were not apparent until a 50-60% reduction in TEER was reached. Disrupted cell layers recovered to their initial TEER value in less than 24 h except after exposure to high concentrations of RAMEB. Perturbations of the Calu-3 cell layers were shown to be dependent on cyclodextrin concentration, as well as chemical derivatisation, and were reversible in all but the most severe cases.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Bosquillon, C
Belhadj Salem, L
Hernandez, E
Martin, G.P
Delattre, Luc ; Université de Liège - ULiège > Département de pharmacie > Département de pharmacie
Evrard, Brigitte ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Forbes, B
Language :
English
Title :
Effect of ß-Cyclodextrin Derivatives on Bronchial Epithelial Cell Layer Permeability
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