Investigation of the enhancing mechanism of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate effect on the intestinal permeability of polar molecules utilizing a voltage clamp method

The intestinal permeability of 6-CF was increased two-fold in the presence of 33-66 mM SNAC, and by 6.5-fold in the presence of 10 mM EDTA. The voltage clamp experiments show that the effect of SNAC was particularly on the transcellular 7-folds increase (that was five times larger than the paracellular transport of the model agent). While EDTA affected predominantly paracellular pathway transport, SNAC 33-66 mM had no effect on [3H]-mannitol transport or any toxic effect on tissue integrity measured by TEER values. In conclusion, this study demonstrates that SNAC can facilitate passive transport of polar charged molecules through the membrane of epithelial enterocytes. This is noteworthy in view of the very low tendency of a charged molecule to permeate across the lipophilic inter-phase of the enterocytes membrane.