Polymeric Sorbents for Bile Acids. 5. Polyacrylamide Resins with Ammonium-Containing Pendants

Abstract

Isotherms have been determined for the sorption of bile salt anions, generally glychocolate (GCA - ), in Tris buffer by cross-linked polyacrylamide resins with ammonium-containing pendent groups having the general structure of P-{(CH 2 ) n N + R 2 Cl - }mR, where R is H or a CH 3 group, and n and m are integers in the range of 2-12 and 1-3, respectively. The sorption capacity increases with the number of ammonium groups per pendant, in accord with the primary importance of electrostatic interactions. In general, the binding affinity of the resins for GCA - also increases with an increase in the hydrophobicity of the pendants. The isotherms for the binding of GCA - by the resins with long hydrophobic spacers have a normal Langmuir shape, while a distinct S-shape is observed for the sorption by resins with shorter spacers. The S-shaped isotherms indicate a positive cooperativity in the binding, probably due to hydrophobic interactions and H-bonding among bile salt anions bound at adjacent positions within the resin beads. On the basis of the sorption characteristics, it is proposed that the binding is accompanied by the development of a considerable degree of order within the beads, involving either the formation of pendent group-bile salt anion reversed mixed micelles or conventional micelles, depending on pendant structure. The resins with C 12 spacers exhibit binding properties that are significantly superior to those of cholestyramine, the bile acid sequestrant currently used clinically for the treatment of hypercholesterolemia.