Effects of the permeability enhancers, tetradecylmaltoside and dimethyl-β-cyclodextrin, on insulin movement across human bronchial epithelial cells (16HBE14o-)

The permeability of human bronchial epithelial cells (16HBE14o(-)) to radiolabelled insulin ([I-125]insulin) formulated in the absence or presence of two different saccharide-containing permeability enhancers was investigated. In the absence of either enhancer, mannitol permeability and transepithelial electrical resistance (R-TE) remained essentially unaffected for the duration of a 2-h experiment. Addition of either 0.125% tetradecylmaltoside (TDM) or 1% dimethyl-beta-cyclodextrin (DMBCD) to the apical surface of cells resulted in increased mannitol permeability and decreased R-TE suggesting a loosening of cellular tight junctions and a concomitant increase in paracellular movement. Addition of [I-125]insulin to the apical side of 16HBE14o(-) cells in the absence or presence of 1% DMBCD resulted in little or no [I-125] insulin movement to the basolateral chamber or degradation in the apical chamber. However, in the presence of 0.125% TDM, the amount of intact [I-125]insulin remaining in the apical chamber was substantially decreased, while [I-125]insulin and I-125-labeled fragments were recovered on the basolateral side of the cells after 2 h. These findings provide evidence that the loosening of the tight junctions between cells achieved with DMBCD is not sufficient to stimulate transepithelial insulin movement, whereas exposure to 0.125% TDM causes an increase in [I-125]insulin permeation and degradation. (C) 2003 Elsevier B.V. All rights reserved.