Oral administration of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) has been reported to increase the bioavailability of various macromolecules. The present study was aimed to study the effect of SNAC on the intestinal tissue permeability of polar charged molecules, using 6-carboxy-fluorescein (6-CF) as a model. The effects of SNAC on rat intestinal permeability was investigated ex vivo by utilizing voltage clamp experiments in a side-by-side diffusion chamber model in comparison with the effect of EDTA (10 mM). 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.
Bibliographical noteFunding Information:
This work is a part of Shmuel Hess Ph.D dissertation. This work was supported by Emisphere Technologies, Inc. The authors thank Dr. Josh Backon for constructive comments. A. Hoffman is affiliated with David R. Bloom Center of Pharmacy.
- Diffusion chamber
- Intestinal absorption
- Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC)
- Voltage clamp