Study of the interaction between modified cyclodextrin and octopriox : potential applications in drug delivery

Original Article


Host–guest interactions between the antifungal agent Octopirox® (Oc) and modified β-cyclodextrin-derivatives were studied using 1H- and 2D-ROESY NMR spectroscopy, Job-Plot and isothermal titration calorimetry (ITC). In addition to β-cyclodextrin (β-CD) a number of derivatives, namely randomly methacrylated β-cyclodextrin (RM-β-CD), mono-methacrylated β-cyclodextrin (MM-β-CD), randomly methylated β-cyclodextrin (RAMEB), hydroxypropyl-β-cyclodextrin (HP-β-CD) and randomly methacrylated hydroxypropyl-β-cyclodextrin (RM-HP-β-CD) were used. NMR data suggests the formation of highly ordered complexes, while ITC measurements allowed the identification of their stoichiometries and the thermodynamic data. To evaluate the possibility of retarded drug release from complexes prepared from polymeric materials like artificial nails, the complexes were polymerized with comonomers and subjected to aqueous extraction followed by quantification of Oc release by means of UV-spectroscopy.


Cyclodextrin Octopirox Pirocton-olamin ITC Methacrylated cyclodextrin Drug release Artificial nails 


  1. 1.
    Futterer, E.: Antidandruff hair tonic containing piroctone olamine. Cosmet. Toilet. 103, 49–52 (1988)Google Scholar
  2. 2.
    Dietrich, G., Bollert, V.: Praxisnahe Prüfmethode für Wirkstoffe gegen vermehrte Schuppung der Kopfhaut. Ärztliche Kosmetologie 10, 34–45 (1980)Google Scholar
  3. 3.
    Futterer, E.: Evaluation of efficacy of antidandruff agents. J. Soc. Cosmet. Chem. 32, 327–338 (1981)Google Scholar
  4. 4.
    Watanabe, Y., Yokoyama, M., Yamada, K., Arima, M., Hori, T., Sagai, M.: Clinical Evaluation of Hair Shampoo and Hair Rinse Containing Piroctone Olamine. J. Jpn. Soc. Cosmet. Sci. 6(2), 79–99 (1982)Google Scholar
  5. 5.
    Futterer, E.: Untersuchung zur Wirksamkeit löslicher Antischuppenwirkstoffe. Ärztliche Kosmetologie 15, 421–435 (1985)Google Scholar
  6. 6.
    Black, J.G., Kamat, V.B.: Percutaneous absorption of octopirox. Food Chem. Toxicol. 26, 53–58 (1988)CrossRefGoogle Scholar
  7. 7.
    Hashimoto, S., Uchino, N., Watari, Y.: Technological progress in formulation and manufacture of medicated shampoo. Fragr J. Special Issue 7, 62–67 (1986)Google Scholar
  8. 8.
    Schrader, K.: Comparative experimental research on dandruff through quantitative image analysis. J. Appl. Cosmetol. 4, 153–170 (1986)Google Scholar
  9. 9.
    Schrader, K., Bielefeldt, S.: Vergleichende experimentelle Untersuchungen von Kopfschuppen mit der quantitativen Bildanalyse. Parfümerie und Kosmetik 68, 72–80 (1987)Google Scholar
  10. 10.
    Myfungar® Nail polish; Polichem SA, Lugano (Switzerland); distributed by Taurus Pharma GmbH, Frankfurt/Main (Germany)Google Scholar
  11. 11.
    Dubini, F., Belotti, M.G., Frangi, A., Monit, D., Saccomani, L.: In vitro antimycotic activity and nail permeation models of a piroctone olamine (octopirox) containing transungual water soluble technology. Arzneim.-Forsch./Drug Res. 55(8), 478–483 (2005)Google Scholar
  12. 12.
    Gröger, M., et. Al.: Cyclodextrine. Accessed 1 Oct 2012
  13. 13.
    Szejtli, J.: Introduction and general overview of cyclodextrin chemistry. Chem. Rev. 98, 1743–1753 (1998)CrossRefGoogle Scholar
  14. 14.
    Ritter, H., Tabatabei, M.: Grüne Polymerchemie—polymerisationsverfahren in Wasser unter Verwendung von Cyclodextrinen. Accessed 1 Oct 2012
  15. 15.
    Forrest, M.L., Gabrielson, N., Pack, D.W.: Cyclodextrin–polyethylenimine conjugates for targeted in vitro gene delivery. Biotechnol. Bioeng. 89, 416–423 (2005)CrossRefGoogle Scholar
  16. 16.
    Kretschmann, O., Choi, S.W., Miyauchi, M., Tomatsu, I., Harada, A., Ritter, H.: Switchable hydrogels obtained by supramolecular cross-linking of adamantyl-containing LCST copolymers with cyclodextrin dimers. Angew. Chem. Int. Ed 45, 4361–4365 (2006)CrossRefGoogle Scholar
  17. 17.
    Kretschmann, O., Ritter, H.: Copolymerization of fluorinated monomers with hydrophilic monomers in aqueous solution in presence of cyclodextrin. Macromol. Chem. Phys. 207, 987–992 (2006)CrossRefGoogle Scholar
  18. 18.
    Antonietti, L., Aymonier, C., Schlotterbeck, U., Garamus, V.M., Maksimova, T., Richtering, W., Mecking, S.: Core-shell-structured highly branched poly(ethylenimine amide)s: synthesis and structure. Macromolecules 38, 5914–5920 (2005)CrossRefGoogle Scholar
  19. 19.
    Maciollek, A., Munteanu, M., Ritter, H.: New generation of polymeric drugs: copolymer from NIPAAM and cyclodextrin methacrylate containing supramolecular-attached antitumor derivative. Macromol. Chem. Phys. 211, 245–249 (2010)CrossRefGoogle Scholar
  20. 20.
    Zhou, J., Ritter, H.: Cyclodextrin functionalized polymers as drug delivery systems. Polym. Chem. 1, 1552–1559 (2010)CrossRefGoogle Scholar
  21. 21.
    Valentino, J.S., Quanren, H.: Cyclodextrins. Toxicol. Pathol. 36, 30–42 (2008)CrossRefGoogle Scholar
  22. 22.
    Dos Santos, J.-F.R., Couceiro, R., Concheiro, A., Torres-Labandeira, J–.J., Alvarez-Lorenzo, A.: Poly(hydroxyethyl methacrylate-co-methacrylated-b-cyclodextrin) hydrogels: synthesis, cytocompatibility, mechanical properties and drug loading/release properties. Acta Biomater. 4, 745–755 (2008)CrossRefGoogle Scholar
  23. 23.
    Uekama, K.: Design and evaluation of cyclodextrin-based drug formulation. Chem. Pharm. Bull. 52, 900–915 (2004)CrossRefGoogle Scholar
  24. 24.
    Hoare, T.R., Kohane, D.S.: Hydrogels in drug delivery: progress and challenges. Polymer 49, 1993–2007 (2008)CrossRefGoogle Scholar
  25. 25.
    Bouchemal, K.: Drug Discov Today 13, 960–972 (2008)CrossRefGoogle Scholar
  26. 26.
    Denadai, A.M.L., Santoro, M.M., Da Silva, L.H., Viana, A.T., Dos Santos, R.A.S., Sinisterra, R.D.J.: Self-assembly Characterization of the β-cyclodextrin and hydrochlorothiazide system: NMR, phase solubility, ITC and QELS. Inclusion Phenom. Macrocyl. Chem. 55, 41–49 (2006)CrossRefGoogle Scholar
  27. 27.
    Teixeira, L.R., Sinisterra, R.D., Vieira, R.P., Scarlatelli-Lima, A., Moraes, M.F.D., Doretto, M.C., Denadai, A.M., Beraldo, H.: An Inclusion compound of the anticonvulsant sodium valproate into a-cyclodextrin: physico-chemical haracterization. J. Inclusion Phenom. Macrocycl. Chem. 54, 133–138 (2006)CrossRefGoogle Scholar
  28. 28.
    Schneider, H.J., Hacket, F., Rudiger, V., Ikeda, H.: NMR studies of cyclodextrins and cyclodextrin complexes. Chem. Rev. 98, 1755–1785 (1998)CrossRefGoogle Scholar
  29. 29.
    Rahman, A.: One and two dimensional NMR spectroscopy, 1st edn. Elsevier, New York (1989)Google Scholar
  30. 30.
    Ohga, K., Takashima, Y., Takashima, H., Kawaguchi, Y., Yamaguchi, H., Harada, A.: Preparation of supramolecular polymers from a cyclodextrin dimer and ditopic guest molecules: control of structure by linker flexibility. Macromolecules 38, 5897–5904 (2005)CrossRefGoogle Scholar
  31. 31.
    Kretschmann, O.: Diss., Assoziative Hydrogele und thermosensitive Polymer-Einschlussverbindungen auf Basis von adamantylhaltigen Polymeren und Cyclodextrinen, 95–98 (2006)Google Scholar
  32. 32.
    Loftsson, T., Brewster, M.E.: Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J. Pharm. Sci. 85, 1017–1025 (1996)CrossRefGoogle Scholar
  33. 33.
    Thompson, D.O.: Cyclodextrins–enabling excipients: their present and future use in pharmaceuticals. Crit. Rev. Ther. Drug Carrier Syst. 14, 1–104 (1997)CrossRefGoogle Scholar
  34. 34.
    Rekharsky, M.V., Inoue, Y.: Complexation thermodynamics of cyclodextrins. Chem. Rev. 98, 1875–1917 (1998)CrossRefGoogle Scholar
  35. 35.
    Rekharsky, M.V., Yamamura, H., Kawai, M., Inoue, Y.: Complexation and chiral recognition thermodynamics of gamma-cyclodextrin with N-acetyl- and N-carbobenzyloxy-dipeptides possessing two aromatic rings. J. Org. Chem. 68, 5228–5235 (2003)CrossRefGoogle Scholar
  36. 36.
    Praefcke, G.J.K.: Isotherme Titrationskalorimetrie (ITC) zur Charakterisierung biomolekularer Wechselwirkungen. BIOspektrum 1, 44–47 (2005)Google Scholar
  37. 37.
    Turnbull, W.B., Daranas, A.H.: On the value of c: can low affinity systems be studied by isothermal titration calorimetry? J. Am. Chem. Soc. 125, 14859–14866 (2003)CrossRefGoogle Scholar
  38. 38.
    Harrison, J.C.: Cyclodextrin–adamantanecarboxylate inclusion complexes: a model system for the hydrophobic effect. Biopolymers 21, 1153–1166 (1982)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Institute for Organic and Macromolecular Chemistry IIHeinrich-Heine-University DüsseldorfDüsseldorfGermany
  2. 2.Medical Faculty, Centre of Dentistry, Department of Operative and Preventive Dentistry and EndodonticsHeinrich-Heine-University DüsseldorfDüsseldorfGermany

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