Thermodynamics of complexation of tauro- and glyco-conjugated bile salts with two modified β-cyclodextrins

Abstract

The interaction between two modified β-cyclodextrins and bile salts, common for rat, dog and man, was studied using isothermal titration calorimetry. The structural differences in the interaction were investigated by 13C NMR. The two modified β-cyclodextrins were chosen because of their frequent use as oral excipients in drug formulation and in marketed products. All the investigated bile salts had an affinity for the β-cyclodextrins, although there were large variations in the stability constants. The variations in the enthalpic and entropic contributions to the overall Gibbs free energy revealed differences in the binding mode to the investigated bile salts, i.e. the bile salts with a hydroxyl group at C12 interacted differently than bile salts without this hydroxyl group. These observations were supported by 13C NMR, which suggested binding to the D-ring of the steroid structure for bile salts with a hydroxyl group at C12 and to the C-ring for the bile salts without this hydroxyl group. The type of substitution of β-cyclodextrin had significant effects on the thermodynamics of the interaction where especially the entropic changed were affected.