Anticancer effect of docetaxel/hydroxypropyl-beta-cyclodextrin complex without histamine release

Original Article


In this study, the anticancer effect and improved safety for hypesensitivity reactions of docetaxel/hydroxypropyl-beta-cyclodextrin complex (DCX-CD) were investigated. The preparation of DCX-CD was confirmed by using differential scanning calorimetry, X-ray powder diffraction analysis, and scanning electron microscope. The anticancer activity was tested in human lung cancer A549 cell-transplanted mice and the hypersensitivity was tested in Beagle dogs after intravenous administration of DCX-CD, Taxotere, and their respective vehicles. In the hypersensitivity test, plasma histamine levels were determined using an ELISA method. Our results showed that DCX-CD was pharmacologically equivalent to Taxotere. Furthermore, DCX-CD did not cause the release of histamines or any significant symptoms associated with hypersensitivity. These results suggested that DCX-CD could be a promising alternative to Taxotere for cancer chemotherapy with reduced side effects.


Docetaxel HP-β-CD Anticancer activity Hypersensitivity 



This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry (NRF-2014R1A1A1A05002840).

Supplementary material

10847_2015_571_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (docx 15 kb)


  1. 1.
    Hennenfent, K.L., Govindan, R.: Novel formulations of taxanes: a review. Old wine in a new bottle? Ann. Oncol. 17, 735–749 (2006)CrossRefGoogle Scholar
  2. 2.
    Engels, F.K., Mathot, R.A., Verweij, J.: Alternative drug formulations of docetaxel: a review. Anticancer Drugs 18, 95–103 (2007)CrossRefGoogle Scholar
  3. 3.
    Baker, J., Ajani, J., Scotté, F., Winther, D., Martin, M., Aapro, M.S., von Minckwitz, G.: Docetaxel-related side effects and their management. Eur. J. Oncol. Nurs. 13, 49–59 (2009)CrossRefGoogle Scholar
  4. 4.
    van Zuylen, L., Verweij, J., Sparreboom, A.: Sparreboom, role of formulation vehicles in taxane pharmacology. Invest. New Drugs 19, 125–141 (2001)CrossRefGoogle Scholar
  5. 5.
    Masini, E., Planchenault, J., Pezziardi, F., Gautier, P., Gagnol, J.P.: Histamine-releasing properties of Polysorbate 80 in vitro and in vivo: correlation with its hypotensive action in the dog. Agents Actions 16, 470–477 (1985)CrossRefGoogle Scholar
  6. 6.
    El-Hashim, A.Z., Jacques, C.A., Herd, C.M., Lee, T.H., Page, C.P.: The effect of R 15.7/HO, an anti-CD18 antibody, on the late airway response and airway hyperresponsiveness in an allergic rabbit model. Br. J. Pharmacol. 121, 671–678 (1997)CrossRefGoogle Scholar
  7. 7.
    Gaoe, H., Pang, Z., Pan, S., Cao, S., Yang, Z., Chen, C., Jiang, X.: Anti-glioma effect and safety of docetaxel-loaded nanoemulsion. Arch. Pharm. Res. 35, 333–341 (2012)CrossRefGoogle Scholar
  8. 8.
    Zhang, L., Zhang, N.: How nanotechnology can enhance docetaxel therapy. Int. J. Nanomed. 8, 2927–2941 (2013)CrossRefGoogle Scholar
  9. 9.
    Huang, X.X., Zhou, C.L., Wang, H., Chen, C., Yu, S.Q., Xu, Q., Zhu, Y.Y., Ren, Y.: Pharmacokinetics, efficacy, and safety evaluation of docetaxel/hydroxypropyl-sulfobutyl-β-cyclodextrin inclusion complex. AAPS PharmSciTech. 12, 665–672 (2011)CrossRefGoogle Scholar
  10. 10.
    Mazzaferro, S., Bouchemal, K., Gallard, J.F., Iorga, B.I., Cheron, M., Gueutin, C., Steinmesse, C., Ponchel, G.: Bivalent sequential binding of docetaxel to methyl-β-cyclodextrin. Int. J. Pharm. 416, 171–180 (2011)CrossRefGoogle Scholar
  11. 11.
    Sun, L., Zhou, D.S., Zhang, P., Li, Q.H., Liu, P.: Gemcitabine and γ-cyclodextrin/docetaxel inclusion complex-loaded liposome for highly effective combinational therapy of osteosarcoma. Int. J. Pharm. 478, 308–317 (2014)CrossRefGoogle Scholar
  12. 12.
    Ferrati, S., Nicolov, E., Bansal, S., Hosali, S., Landis, M., Grattoni, A.: Docetaxel/2-hydroxypropyl β-cyclodextrin inclusion complex increases docetaxel solubility and release from a nanochannel drug delivery system. Curr. Drug Targets (2015). doi: 10.2174/1389450116666150223124809 Google Scholar
  13. 13.
    Gould, S., Scott, R.C.: 2-Hydroxypropyl-beta-cyclodextrin (HP-beta-CD): a toxicology review. Food Chem. Toxicol. 43, 1451–1459 (2005)CrossRefGoogle Scholar
  14. 14.
    Kim, T.K., Yoo, H.H., Kim, E.J., Lee, B.Y., Park, J.H.: Pharmacokinetic equivalence of Taxotere and SID530, a novel docetaxel formulation containing hydroxypropyl-beta-cyclodextrin in monkeys. Arzneimittelforschung 62, 280–284 (2012)CrossRefGoogle Scholar
  15. 15.
    Kim, T.K., Kim, I.S., Yoo, H.H.: Determination of docetaxel in rat plasma and its application in the comparative pharmacokinetics of Taxotere and SID530, a novel docetaxel formulation with hydroxypropyl-β-cyclodextrin. Biomed. Chromatogr. 27, 306–310 (2013)Google Scholar
  16. 16.
    Kim, T.K., Yoo, H.H., Kim, E.J., Sa, J.H., Lee, B.Y., Park, J.H.: Comparative protein binding of taxotere and SID530, a new docetaxel formulation with hydroxypropyl-beta-cyclodextrin, in human plasma in vitro. Pharmazie 67, 789–791 (2012)Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.College of Science & EngineeringJungwon UniversityChungbukRepublic of Korea
  2. 2.Institute of Pharmaceutical Science and Technology and College of PharmacyHanyang UniversityAnsanRepublic of Korea

Personalised recommendations