Enhancing the "stickiness" of bile acids to cross-linked polymers: A bioconjugate approach to the design of bile acid sequestrants

A series of cross-linked polymers have been synthesized by reaction of 2% c ross-linked, chloromethylated polystyrene with a tertiary amine derivative (7) of cholic acid (prepared by reaction of cholic acid methyl ester with N ,N-dimethyl-ethylenediamine), followed by exhaustive quaternization with tr imethylamine. Increased loadings of 7 result in enhanced binding of tauroch olate ion and a decrease in its rate of release upon exposure to 50 mM aque ous NaCl. Examination of particle-size effects indicates that film diffusio n and particle diffusion both contribute to the observed kinetics. Interrup tion tests that were carried out confirmed that particle diffusion is kinet ically important. The relevance of this bioconjugate approach to the design of bile acid sequestrants for the treatment of hypereholesterolemia is bri efly discussed.