The absorption of retinoic acids from the gastrointestinal tract is dependent upon chemical structure

Purpose: The gastrointestinal permeability of a number of retinoic acids was determined in order to evaluate whether the gastrointestinal membrane was able to distinguish between retinoids in which the polyene chain was present in several different isomeric forms. In addition, the structure of the six-membered ring was varied in order to determine which portion of the molecule was most important for its recognition by the membrane. The role of bile salt micelle composition in the intestinal absorption of retinoids was also evaluated. Methods: In situ perfused rat intestinal segment preparations (n = 78) were used, and the retinoids were each perfused at a concentration of approximately 1 μg/ml in either simple micelles of sodium taurocholate (10 mM) or mixed micelles of sodium taurocholate/egg phosphatidylcholine (10 mM/10 mM). The flow rate of the perfusate was either 0.1 or 0.35 ml/min. Results: For each retinoid, the mixed micelles were associated with a higher degree of retinoid uptake into the jejunal cells than were the simple micelles. In addition, the permeability was higher when the perfusate flow was greater, indicating that the aqueous boundary layer of the intestine contributes to the resistance to the disappearance of the retinoid from the intestinal lumen. Retinoid structure was also found to have a significant effect on the permeability in the mixed micelle systems at both low and high flow rates, but not with simple micelles. The structure of the six-membered ring was not a major determinant of the permeability. However, the permeability of the retinoids with the polyene chain in the 13-cis position was significantly greater than when the chain was all-trans or in the 9-cis position. Conclusions: The isomeric position of the polyene chain and the presence of phospholipid in the micellar vehicle have a significant influence on the membrane transport of the retinoic acids.