Paper Citing NAMD - Abstract
Holm, Rene; Ostergaard, Jesper; Schonbeck, Christian; Jensen, Henrik; Shi, Wei; Peters, Gunther H.; Westh, Peter
Determination of stability constants of tauro- and glyco-conjugated bile salts with the negatively charged sulfobutylether-beta-cyclodextrin: comparison of affinity capillary electrophoresis and isothermal titration calorimetry and thermodynamic analysis of the interaction
JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY, 78:185-194, APR 2014
The aim of the present work was to investigate the interaction between bile salts present in the intestine of man, dog and rat with the negatively charged cyclodextrin (CD), sulfobutylether-beta-cyclodextrin (SBE beta CD). The interactions between bile salts and CDs are of importance for the release of CD-complexed drugs upon oral administration. This makes a good understanding of this particular interaction important for rational drug formulation. SBE beta is a modified CD, which has attracted particular interest in formulation science. It is unique in the sense that it carries approximately seven negatively charged side chains, which can potentially interact electrostatically with the guest molecule. Bile salts are negatively charged at physiological pH, and the concomitant repulsion from SBE beta CD could potentially reduce their affinity for this CD and hence their ability to expel drugs delivered as SBE beta CD complexes. However, this study has demonstrated that the interaction, between a bile salts and SBE beta CD is only slightly weaker than the corresponding interactions with natural beta CD. Significant differences between the thermodynamics of bile salt complexes with respectively HP beta CD and SBE beta CD were found, when comparing the same degree of substitution. This underscores the importance of the substituents on the interactions of modified CDs with bile salts.
