THE MUCUS LAYER AS A BARRIER TO DRUG ABSORPTION IN MONOLAYERS OF HUMAN INTESTINAL EPITHELIAL HT29-H GOBLET CELLS

The efficacy of the intestinal mucus layer as a barrier to drug absorption was investigated in monolayers of a mucus-producing human goblet cell line (HT29-H) using testosterone as a model drug. The investigation included comparison of the permeability of the HT29-H monolayers to testosterone before and after removal of the mucus layer, and comparison of the permeability of HT29-H and mucus-free Caco-2 cell monolayers. The apparent permeability coefficients of testosterone in HT29-H monolayers were 6.8 +/- 1.0 X 10(-6) cm/s before and 21.5 +/- 5.9 x 10(-6) cm/s after removal of the mucus layer (p < 0.02). The corresponding permeability coefficients in Caco-2 monolayers were 31.5 +/- 5.3 x 10(-6) and 32.1 +/- 9.3 x 10(-6) cm/s (p > 0.05) or approx. 50% higher than that of 'mucus-free' HT29-H monolayers. A comparison of the relative importance of the mucus layer, the unstirred water layer and the goblet cell monolayer as barriers to testosterone absorption showed that the mucus layer contributes 78% of the total resistance to absorption. We conclude that the intestinal mucus layer produced by HT29-H goblet cells is a significant barrier to testosterone absorption and that HT29-H monolayers can be used to study the barrier functions of an intact human intestinal mucus layer in cell culture.