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Mechanism of cholesterol gallstone dissolution. I. The determination of the binding of alkyl amines to bile micelles using dynamic membrane transport methods

Journal of Colloid and Interface Science
Publication Date
DOI: 10.1016/0021-9797(80)90184-8


Abstract Recent studies have shown that cholesterol monohydrate pellet dissolution rates in real and synthetic bile systems are enhanced dramatically in the presence of small concentrations of amines (primary, secondary, and tertiary), quaternary ammonium compounds, and cationic surfactants. These studies have shown that, in general, chain length, the degree of hydrophobicity, the ability to alter micellar charge, as well as the steric or structural features of these molecules seem to be important. In all of the past studies, however, the situations have been complicated by the fact that the accelerator molecules in question were bound to varying degrees to the micelles and other components of the synthetic bile. Meaningful structure activity relationships can only be considered when the concentrations of bound and unbound drug are known. A dynamic cellulose membrane dialysis technique was used; in evaluating the validity of the technique for the present purposes the following factors were considered: (a) the possible influence of membrane charge on dialysis, (b) the possible influence of bile acid-lecithin micelles on dialysis rate, (c) the possible influence of pore size and molecular structure on dialysis rate, and finally (d) the influence of Donnan membrane effects. Some of the results obtained using this technique were compared to the results obtained using the silicone rubber membrane system. There is very good agreement between the data obtained using the two methods. Thus, the good agreement underscores the validity of either method and rules out, for example, the possibility that an amine-chenodeoxycholate complex is being transported across either or both membranes.

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