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

Rene Holm, Jesper Østergaard, Jens Christian Sidney Schönbeck, Henrik Jensen, Wei Shi, Günther H. Peters, Peter Westh

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    Resumé

    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
    OriginalsprogEngelsk
    TidsskriftJournal of Inclusion Phenomena and Macrocyclic Chemistry
    Vol/bind78
    Udgave nummer1-4
    Sider (fra-til)185-194
    ISSN1388-3127
    DOI
    StatusUdgivet - 2014

    Citer dette

    @article{8d57a15eb9e54efcacfc58b8b663bf26,
    title = "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",
    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",
    author = "Rene Holm and Jesper {\O}stergaard and Sch{\"o}nbeck, {Jens Christian Sidney} and Henrik Jensen and Wei Shi and Peters, {G{\"u}nther H.} and Peter Westh",
    year = "2014",
    doi = "10.1007/s10847-013-0287-0",
    language = "English",
    volume = "78",
    pages = "185--194",
    journal = "Journal of Inclusion Phenomena and Macrocyclic Chemistry",
    issn = "1388-3127",
    publisher = "Springer Netherlands",
    number = "1-4",

    }

    TY - JOUR

    T1 - 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

    AU - Holm, Rene

    AU - Østergaard, Jesper

    AU - Schönbeck, Jens Christian Sidney

    AU - Jensen, Henrik

    AU - Shi, Wei

    AU - Peters, Günther H.

    AU - Westh, Peter

    PY - 2014

    Y1 - 2014

    N2 - 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

    AB - 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

    U2 - 10.1007/s10847-013-0287-0

    DO - 10.1007/s10847-013-0287-0

    M3 - Journal article

    VL - 78

    SP - 185

    EP - 194

    JO - Journal of Inclusion Phenomena and Macrocyclic Chemistry

    JF - Journal of Inclusion Phenomena and Macrocyclic Chemistry

    SN - 1388-3127

    IS - 1-4

    ER -