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 absorp tion was investigated in monolayers of a mucus-producing human goblet cell line (HT29-H) using testosterone as a model drug. The investigati on included comparison of the permeability of the HT29-H monolayers to testosterone before and after removal of the mucus layer, and compari son of the permeability of HT29-H and mucus-free Caco-2 cell monolayer s. The apparent permeability coefficients of testosterone in HT29-H mo nolayers 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 t han that of 'mucus-free' HT29-H monolayers. A comparison of the relati ve importance of the mucus layer, the unstirred water layer and the go blet 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 goble t cells is a significant barrier to testosterone absorption and that H T29-H monolayers can be used to study the barrier functions of an inta ct human intestinal mucus layer in cell culture.