Skip to main content
SpringerLink
Log in

Inclusion of chemotherapeutic agents in substituted β-cyclodextrin derivatives

  • Original Article
  • Published:
Journal of Inclusion Phenomena and Macrocyclic Chemistry Aims and scope Submit manuscript

Abstract

The stabilities of the inclusion compounds of three chemotherapeutic agents, camptothecin (CPT), docetaxel (DOC) and idarubicin (IDA), plus a model compound 1,4-dihydroxyanthraquinone (DHA) with several β-cyclodextrin (β-CD) derivatives were investigated by solubility measurements, isothermal titration microcalorimetry and fluorescence anisotropy measurements. Ionic heptakis-(6-deoxy-6-thioethers) of β-CD were found to exhibit very high binding potentials for these drugs making them to good candidates for advanced drug delivery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

CD:

Cyclodextrin

CPT:

Camptothecin

DHA:

1, 4-Dihydroxyanthraquinone

DOC:

Docetaxel

HPβCD:

Hydroxypropyl-β-cylodextrin

IDA:

Idarubicin

ITC:

Isothermal titration calorimetry

References

  1. Wenz, G.: Cyclodextrins as building blocks for supramolecular structures and functional units. Angew. Chem., Int. Ed. 33, 803–822 (1994)

    Article  Google Scholar 

  2. Müller, A., Wenz, G.: Thickness recognition of bola-amphiphiles by α-cyclodextrin. Chem. Eur. J. 13, 2218–2223 (2007)

    Article  Google Scholar 

  3. Szejtli, J.: Introduction and general overview of cyclodextrin chemistry. Chem. Rev. 98, 1743–1753 (1998)

    Article  CAS  Google Scholar 

  4. Wenz, G.: An overview of host–guest chemistry and its application to nonsteroidal anti-inflammatory drugs. Clin. Drug Investig. 19(Suppl 2), 21–25 (2000)

    Article  CAS  Google Scholar 

  5. Davis, M.E., Brewster, M.E.: Cyclodextrin-based pharmaceutics: past, present and future. Nat. Rev. Drug Discov. 3, 1023–1035 (2004)

    Article  CAS  Google Scholar 

  6. Holland, L., Rizzi, G., Malton, P.: Cosmetic compositions containing cyclic oligosaccharides for long-lasting fragrances. Patent WO 2000067717. The Procter and Gamble Company. PCT Int. Appl., 2000

  7. Desiderio, C., Fanali, S.: Use of negatively charged sulfobutyl ether-β-cyclodextrin for enantiomeric separation by capillary electrophoresis. J. Chromatogr. A. 716, 183–196 (1995)

    Article  CAS  Google Scholar 

  8. Mikus, P., Kaniansky, D., Fanali, S.: Separation of multicomponent mixtures of 2,4-dinitrophenyl labelled amino acids and their enantiomers by capillary zone electrophoresis. Electrophoresis 22, 470–477 (2001)

    Article  CAS  Google Scholar 

  9. Connors, K.A.: The stability of cyclodextrin complexes in solution. Chem. Rev. 97, 1325–1357 (1997)

    Article  CAS  Google Scholar 

  10. Frijlink, H.W., Eissens, A.C., Hefting, N.R., Poelstra, K., Lerk, C.F., Meijer, D.K.F.: The effect of parenterally administered cyclodextrins on cholesterol level in the rat. Pharm. Res. 8, 9–16 (1991)

    Article  CAS  Google Scholar 

  11. Irie, T., Uekama, K.: Pharmaceutical applications of cyclodextrins. 3. Toxicological issues and safety evaluation. J. Pharm. Sci. 86, 147–162 (1997)

    Article  CAS  Google Scholar 

  12. Stella, V.J., Rajewski, R.A.: Cyclodextrins: their future in drug formulation and delivery. Pharm. Res. 14, 556–567 (1997)

    Article  CAS  Google Scholar 

  13. Kitae, T., Nakayama, T., Kano, K.: Chiral recognition of α-amino acids by charged cyclodextrins through cooperative effects of coulomb interaction and inclusion. J. Chem. Soc., Perkin Trans. 2, 207–212 (1998)

    Google Scholar 

  14. Wenz, G., Strassnig, C., Thiele, C., Engelke, A., Morgenstern, B., Hegetschweiler, K.: Recognition of ionic guests by ionic b-cyclodextrin derivatives. Chem. Eur. J. 14, 7202–7211 (2008)

    Article  CAS  Google Scholar 

  15. Lundberg, B.B.: Biologically active camptothecin derivatives for incorporation into liposome bilayers and lipid emulsions. Anti-Cancer Drug Des. 13, 453 (1998)

    CAS  Google Scholar 

  16. Kang, J., Kumar, V., Yang, D., Chowdhury, P.R., Hohl, R.J.: Cyclodextrin complexation: influence on the solubility, stability, and cytotoxicity of camptothecin, an antineoplastic agent. Eur. J. Pharm. Sci. 15, 163–170 (2002)

    Article  CAS  Google Scholar 

  17. Steffen, A., Thiele, C., Tietze, S., Strassnig, C., Kämper, A., Lengauer, T., Wenz, G., Apostolakis, J.: Improved cyclodextrin based receptors for camptothecin by inverse virtual screening. Chem. Eur. J. 13, 6801–6809 (2007)

    Article  CAS  Google Scholar 

  18. Lyseng-Williamson, K.A., Fenton, C.: Docetaxel—a review of its use in metastatic breast cancer. Drugs 65, 2513–2531 (2005)

    Article  CAS  Google Scholar 

  19. Figitt, D.P., Wiseman, L.R.: Docetaxel—an update of its use in advanced breast cancer. Drugs 59, 621–651 (2000)

    Article  Google Scholar 

  20. Defaye, J., Ortiz-Mellet, C., Fernandez, J.M.G., Maciejewski, S.: Thioureido-β-cyclodextrins as molecular carriers for the anticancer drug taxotere. In: Coleman, A.W. (ed.) Proceedings of the Ninth International Symposium on Molecular Recognition and Inclusion, pp. 313–316. Kluwer Acad. (1998)

  21. Benito, J.M., Gómez-García, M., Mellet, C.O., Baussanne, I., Defaye, J., García Fernández, J.M.: Optimizing saccharide-directed molecular delivery to biological receptors: design, synthesis, and biological evaluation of glycodendrimer-cyclodextrin conjugates. J. Am. Chem. Soc. 126, 10355–10363 (2004)

    Article  CAS  Google Scholar 

  22. Di Marino, A., Rubio, L., Mendicuti, F.: Fluorescence and molecular mechanics of 1-methyl naphthalenecarboxylate/cyclodextrin complexes in aqueous medium. J. Incl. Phenom. Macrocycl. Chem. 58, 103–114 (2007)

    Article  Google Scholar 

  23. Hirose, K.: A practical guide for the determination of binding constants. J. Incl. Phenom. Macrocycl. Chem. 39, 193–209 (2001)

    Article  CAS  Google Scholar 

  24. Chmurski, K., Defaye, J.: An improved synthesis of per(6-deoxyhalo)cyclodextrin using N-halosuccinimides-triphenylphosphine in DMF. Supramol. Chem. 12, 221–224 (2000)

    Article  CAS  Google Scholar 

  25. Loftsson, T., Hreinsdottir, D., Masson, M.: Evaluation of cyclodextrin solubilization of drugs. Int. J. Pharm. 302, 18–28 (2005)

    Article  CAS  Google Scholar 

  26. Schneider, H.-J.: Binding mechanisms in supramolecular complexes. Angew. Chem., Int. Ed. 48, 3924–3977 (2009)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank R. Heisel and A. Engelke for technical assistance and the Federal Ministry of Education and Research of Germany (Project Number 13N9133) for financial support.

Author information

Authors and Affiliations

  1. Organic Macromolecular Chemistry, Saarland University, 66123, Saarbrücken, Germany

    Carolin Thiele & Gerhard Wenz

  2. Biophysical Chemistry, Saarland University, 66123, Saarbrücken, Germany

    Dagmar Auerbach & Gregor Jung

Authors
  1. Carolin Thiele
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dagmar Auerbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gregor Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gerhard Wenz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gerhard Wenz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thiele, C., Auerbach, D., Jung, G. et al. Inclusion of chemotherapeutic agents in substituted β-cyclodextrin derivatives. J Incl Phenom Macrocycl Chem 69, 303–307 (2011). https://doi.org/10.1007/s10847-010-9741-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10847-010-9741-4

Keywords

Search

Navigation