Vol. 285, Issue 3, 1175-1180, June 1998

A New Interpretation of Salicylic Acid Transport across the Lipid Bilayer: Implications of pH-Dependent but not Carrier-Mediated Absorption from the Gastrointestinal Tract

Masanori Takagi, Yoko Taki, Toshiyasu Sakane, Tanekazu Nadai, Hitoshi Sezaki, Naoto Oku and Shinji Yamashita

Faculty of Pharmaceutical Sciences, Setsunan University, Nagaotoge-cho, Hirakata, Osaka 573-01, Japan (M.T., Y.T., T.S., T.N., H.S., S.Y.), and School of Pharmaceutical Sciences, University of Shizuoka, Yada, Shizuoka, Shizuoka 422, Japan (N.O.)

Transport of several monocarboxylic acids across the lipid bilayer was examined in liposomes consisting of egg yolk phosphatidylcholine and cholesterol. In the presence of inward proton gradient, salicylic acid (SA) was taken up rapidly by liposomes showing overshoot, saturation and competitive inhibition phenomena. These carrier-mediated like profiles of SA uptake can be explained by assuming a very high permeability through the liposomal membrane of protonated SA. Protonated SA in the extraliposomal solution (pH 5.8) was taken up by liposomes rapidly, followed by a redissociation to anion according to the intraliposomal pH (pH 7.5). The concentration gradient of protonated SA across the liposomal membrane is maintained until the intraliposomal pH decreased to the extraliposomal level, which facilitates the uptake of SA into liposomes. The permeability of the lipid bilayer to several compounds was estimated from the inhibitory effects of those compounds on SA uptake by liposomes. Good linear relationships were observed between their inhibitory effects on the liposomal uptake of SA and the permeability of the intestinal membrane to them determined both in vivo and in vitro. These results clearly indicate that the carrier-independent transport mechanism of monocarboxylic acids observed in liposomes significantly contributes to their absorption from the intestinal tract under physiological conditions.