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Determination of stability constants of tauro- and glyco-conjugated bile salts with the negatively charged sulfobutylether-β-cyclodextrin: comparison of affinity capillary electrophoresis and isothermal titration calorimetry and thermodynamic analysis of the interaction

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Abstract

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-β-cyclodextrin (SBEβCD). 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. SBEβCD 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 SBEβCD could potentially reduce their affinity for this CD and hence their ability to expel drugs delivered as SBEβCD complexes. However, this study has demonstrated that the interaction, between a bile salts and SBEβCD is only slightly weaker than the corresponding interactions with natural βCD. Significant differences between the thermodynamics of bile salt complexes with respectively HPβCD and SBEβCD 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.

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Authors and Affiliations

  1. Biologics and Pharmaceutical Science, H.Lundbeck A/S, Ottiliavej 9, 2500, Valby, Denmark

    René Holm & Christian Schönbeck

  2. Department of Pharmacy, Faculty of Health and Medical Sciences, Copenhagen University, Universitetsparken 2, 2100, Copenhagen, Denmark

    René Holm, Jesper Østergaard & Henrik Jensen

  3. NSM, Research Unit for Functional Biomaterials, Roskilde University, Universitetsvej 1, 4000, Roskilde, Denmark

    Christian Schönbeck, Wei Shi & Peter Westh

  4. Department of Chemistry, Technical University of Denmark, 2800, Kgs. Lyngby, Denmark

    Günther H. Peters

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Holm, R., Østergaard, J., Schönbeck, C. et al. Determination of stability constants of tauro- and glyco-conjugated bile salts with the negatively charged sulfobutylether-β-cyclodextrin: comparison of affinity capillary electrophoresis and isothermal titration calorimetry and thermodynamic analysis of the interaction. J Incl Phenom Macrocycl Chem 78, 185–194 (2014). https://doi.org/10.1007/s10847-013-0287-0

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