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See detailEffect of ß-Cyclodextrin Derivatives on Bronchial Epithelial Cell Layer Permeability
Bosquillon, C; Belhadj Salem, L; Hernandez, E et al

in Delivery to the lung (2006), 17

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 ... [more ▼]

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. [less ▲]

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