Advertisement

Effect of γ-cyclodextrin derivative complexation on the physicochemical properties and antimicrobial activity of hinokitiol

  • Rina Suzuki
  • Yutaka Inoue
  • Yuina Tsunoda
  • Isamu Murata
  • Yasunori Isshiki
  • Seiichi Kondo
  • Ikuo Kanamoto
Original Article

Abstract

The aim of this study was to evaluate the physicochemical properties of solid dispersion on mixtures of hinokitiol (HT) and γ-cyclodextrin (γ-CD) and of HT and (2-hydroxypropyl)-γ-cyclodextrin (HP-γ-CD). Differential scanning calorimetry revealed that coground HT/γ-CD at a molar ratio of 1:1 and HT and HP-γ-CD at molar ratios of 1:1 and 1:2 lacked an endothermic peak due to melting of HT crystals. Powder x-ray diffraction revealed that HT crystal showed a halo pattern respectively, by mixing and grinding of the CDs and HT. Thus, coground HT/γ-CD and HT/HP-γ-CD at a molar ratio of 1:1 had molecular interaction. Assessment of dissolution revealed that ground mixtures had improved dissolution of HT compared to HT crystals, ground HT alone, and physical mixtures containing HT. 1H-1H NOESY NMR suggested that the 7-membered ring and isopropyl group of HT were located within the cavity of γ-CD and HP-γ-CD. The antimicrobial tests indicated that ground mixtures exhibited a minimum inhibitory concentration (MIC) of 20 μg/mL against Bacillus subtilis, 40 μg/mL against Staphylococcus aureus, and 20 μg/mL against Escherichia coli. GMs were found to have 4 times more antimicrobial activity than HT crystals. Ground mixtures also exhibited MIC of 160 μg/mL against Pseudomonas aeruginosa and they were found to 2 times more antimicrobial activity than HT crystals. Improvement in antimicrobial activity with the formation of inclusion complexes is presumably due to increase the solubility of HT as a result of the formation of HT/CD inclusion complexes.

Keywords

Hinokitiol Cyclodextrin Ground mixture Molecular interaction Antimicrobial activity 

Notes

Compliance with ethical standards

Conflicts of interest

The authors declare no conflict interest.

References

  1. 1.
    Oblak, E.Z., Bolstad, E.S., Ononye, S.N., Priestley, N.D., Hadden, M.K., Wright, D.L.: The furan route to tropolones: probing the antiproliferative effects of β-thujaplicin analogs. Org. Biomol. Chem. 10, 8597–8604 (2012)CrossRefGoogle Scholar
  2. 2.
    Komaki, N., Watanabe, T., Ogasawara, A., Sato, N., Mikami, T., Matsumoto, T.: Antifungal mechanism of hinokitiol against Candida albicans. Biol. Pharm. Bull. 31, 735–737 (2008)CrossRefGoogle Scholar
  3. 3.
    Yen, T.B., Chang, H.T., Hsieh, C.C., Chang, S.T.: Antifungal properties of ethanolic extract and its active compounds from Calocedrus macrolepis var. formosana (Florin) heartwood. Bioresour. Technol. 99, 4871–4877 (2008)CrossRefGoogle Scholar
  4. 4.
    Shih, M.F., Chen, L.Y., Tsai, P.J., Cherng, J.Y.: In vitro and in vivo therapeutics of β-thujaplicin on LPS-induced inflammation in macrophages and septic shock in mice. Int. J. Immunopathol. Pharmacol. 25, 39–48 (2012)Google Scholar
  5. 5.
    Koufaki, M., Theodorou, E., Alexi, X., Nikoloudaki, F., Alexis, M.N.: Synthesis of tropolone derivatives and evaluation of their in vitro neuroprotective activity. Eur. J. Med. Chem. 45, 1107–1112 (2010)CrossRefGoogle Scholar
  6. 6.
    Choi, Y.G., Bae, E.J., Kim, D.S., Park, S.H., Kwon, S.B., Na, J.I., Park, K.C.: Differential regulation of melanosomal proteins after hinokitiol treatment. J. Dermatol. Sci. 43, 181–188 (2006)CrossRefGoogle Scholar
  7. 7.
    Liu, S., Yamauchi, H.: p27-Associated G1 arrest induced by hinokitiol in human malignant melanoma cells is mediated via down-regulation of pRb, Skp2 ubiquitin ligase, and impairment of Cdk2 function. Cancer Lett. 286, 240–249 (2009)CrossRefGoogle Scholar
  8. 8.
    Shih, Y.H., Chang, K.W., Hsia, S.M., Yu, C.C., Fuh, L.J., Chi, T.Y., Shieh, T.M.: In vitro antimicrobial and anticancer potential of hinokitiol against oral pathogens and oral cancer cell lines. Microbiol. Res. 168, 254–262 (2013)CrossRefGoogle Scholar
  9. 9.
    Iha, K., Suzuki, N., Yoneda, M., Takeshita, T., Hirofuji, T.: Effect of mouth cleaning with hinokitiol-containing gel on oral malodor: a randomized, open-label pilot study. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 116, 433–439 (2013)CrossRefGoogle Scholar
  10. 10.
    Shih, Y.H., Lin, D.J., Chang, K.W., Hsia, S.M., Ko, S.Y., Lee, S.Y., Hsue, S.S., Wang, T.H., Chen, Y.L., Shieh, T.M.: Evaluation physical characteristics and comparison antimicrobial and anti-inflammation potentials of dental root canal sealers containing hinokitiol in vitro. PLoS ONE 9(6), e94941 (2014)CrossRefGoogle Scholar
  11. 11.
    Okumura, S., Hoshino, M., Joshita, K., Nishnomiya, T., Murata, M.: Hinokitiol inhibits polyphenol oxidase and enzymatic browning. Food Sci. Technol. Res. 17, 251–256 (2011)CrossRefGoogle Scholar
  12. 12.
    Brewster, M.E., Loftsson, T.: Cyclodextrins as pharmaceutical solubilizers. Adv. Drug Deliv. Rev. 59, 645–666 (2007)CrossRefGoogle Scholar
  13. 13.
    Zhang, Q.F., Nie, H.C., Shangguang, X.C., Yin, Z.P., Zheng, G.D., Chen, J.G.: Aqueous solubility and stability enhancement of astilbin through complexation with cyclodextrins. J. Agric. Food Chem. 61, 151–156 (2013)CrossRefGoogle Scholar
  14. 14.
    Zhang, S.X., Fan, M.G., Liu, Y.Y., Ma, Y., Zhang, G.J., Yao, J.N.: Inclusion complex of spironaphthoxazine with gamma-cyclodextrin and its photochromism study. Langmuir 23, 9443–9446 (2007)CrossRefGoogle Scholar
  15. 15.
    Aleem, O., Kuchekar, B., Pore, Y., Late, S.: Effect of beta-cyclodextrin and hydroxypropyl beta-cyclodextrin complexation on physicochemical properties and antimicrobial activity of cefdinir. J. Pharm. Biomed. Anal. 47, 535–540 (2008)CrossRefGoogle Scholar
  16. 16.
    Miyoshi, N., Wakao, Y., Tomono, S., Tatemichi, M., Yano, T., Ohshima, H.: The enhancement of the oral bioavailability of γ-tocotrienol in mice by γ-cyclodextrin inclusion. J. Nutr. Biochem. 22, 1121–1126 (2011)CrossRefGoogle Scholar
  17. 17.
    Martin, A., Tabary, N., Leclercq, L., Junthip, J., Degoutin, S., Aubert-Viard, F., Cazaux, F., Lyskawa, J., Janus, L., Bria, M., Martel, B.: Multilayered textile coating based on a β-cyclodextrin polyelectrolyte for the controlled release of drugs. Carbohydr. Polym. 93, 718–730 (2012)CrossRefGoogle Scholar
  18. 18.
    Tan, Q., Zhang, L., Zhang, L., Teng, Y., Zhang, J.: Design and evaluation of an economic taste-masked dispersible tablet of pyridostigmine bromide, a highly soluble drug with an extremely bitter taste. Chem. Pharm. Bull. 60, 1514–1521 (2012)CrossRefGoogle Scholar
  19. 19.
    Ikuta, N., Sugiyama, H., Shimosegawa, H., Nakane, R., Ishida, Y., Uekaji, Y., Nakata, D., Pallauf, K., Rimbach, G., Terao, K., Matsugo, S.: Analysis of the enhanced stability of r(+)-alpha lipoic Acid by the complex formation with cyclodextrins. Int. J. Mol. Sci. 14, 3639–3655 (2013)CrossRefGoogle Scholar
  20. 20.
    Ogawa, N., Higashi, K., Nagase, H., Endo, T., Moribe, K., Loftsson, T., Yamamoto, K., Ueda, H.: Effects of cogrinding with β-cyclodextrin on the solid state fentanyl. J. Pharm. Sci. 99, 5019–5029 (2010)CrossRefGoogle Scholar
  21. 21.
    Al Omari, A.A., Al Omari, M.M., Badwan, A.A., Al-Sou’od, K.A.: Effect of cyclodextrins on the solubility and stability of candesartan cilexetil in solution and solid state. J. Pharm. Biomed. Anal. 54, 503–509 (2011)CrossRefGoogle Scholar
  22. 22.
    Higuchi, T., Connors, K.A.: Phase-Solubility Techniques. In: Reilly, C.N. (ed.) Advances in Analytical Chemistry and Instrumentation, vol. 4, pp. 117–212. Wiley-Interscience, New York (1965)Google Scholar
  23. 23.
    Job, P.: Formation and stability of inorganic complexes in solution. Ann. Chim. Phys. 9, 113–203 (1928)Google Scholar
  24. 24.
    CLSI Document M7-A7, Approved Standard-Ninth Edition (2006)Google Scholar
  25. 25.
    Takeda, Y., Isshiki, Y., Sakuda, K., Sakuma, K., Kondo, S.: Improved methods for estimation of antimicrobial activities of volatile and hydrophobic fragrance ingredients. J. Jpn. Cosmet. Sci. Soc. 32, 10–17 (2008)Google Scholar
  26. 26.
    Xiao, C.F., Li, K., Huang, R., He, G.J., Zhang, J.Q., Zhu, L., Yang, Q.Y., Jiang, K.M., Jin, Y., Lin, J.: Investigation of inclusion complex of epothilone A with cyclodextrins. Carbohydr. Polym. 102, 297–305 (2014)CrossRefGoogle Scholar
  27. 27.
    Fernandes, C.M., Teresa Vieira, M., eiga, F.J.: Physicochemical characterization and in vitro dissolution behavior of nicardipine-cyclodextrins inclusion compounds. Eur. J. Pharm. Sci. 15, 79–88 (2002)CrossRefGoogle Scholar
  28. 28.
    Mohamad, S., Surikumaran, H., Raoov, M., Marimuthu, T., Chandrasekaram, K., Subramaniam, P.: Conventional study on novel dicationic ionic liquid inclusion with β-cyclodextrin. Int. J. Mol. Sci. 12, 6329–6345 (2011)CrossRefGoogle Scholar
  29. 29.
    Nguyen, T.A., Liu, B., Zhao, J., Thomas, D.S., Hook, J.M.: An investigation into the supramolecular structure, solubility, stability and antioxidant activity of rutin/cyclodextrin inclusion complex. Food Chem. 136, 186–192 (2013)CrossRefGoogle Scholar
  30. 30.
    Negi, J.S., Singh, S.: Spectroscopic investigation on the inclusion complex formation between amisulpride and γ-cyclodextrin. Carbohydr. Polym. 92, 1835–1843 (2003)CrossRefGoogle Scholar
  31. 31.
    Morita, Y., Sakagami, Y., Okabe, T., Ohe, T., Inamori, Y., Ishida, N.: The mechanism of the bactericidal activity of hinokitiol. Biocontrol. Sci. 12, 101–110 (2007)CrossRefGoogle Scholar
  32. 32.
    Zhao, M., Zhu, D., Sun-Waterhouse, D., Su, G., Lin, L., Wang, X., Dong, Y.: Identification of cyclodextrin inclusion complex of chlorogenic acid and its antimicrobial activity. Food Chem. 120, 1138–1142 (2010)CrossRefGoogle Scholar
  33. 33.
    Petralito, S., Zanardi, I., Memoli, A., Annesini, M.C., Travagli, V.: Solubility, spectroscopic properties and photostability of Rhein/cyclodextrin inclusion complex. Spectrochim. Acta. A. Mol. Biomol. Spectrosc. 74, 1254–1259 (2009)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Rina Suzuki
    • 1
  • Yutaka Inoue
    • 1
  • Yuina Tsunoda
    • 1
  • Isamu Murata
    • 1
  • Yasunori Isshiki
    • 2
  • Seiichi Kondo
    • 2
  • Ikuo Kanamoto
    • 1
  1. 1.Laboratory of Drug Safety Management, Faculty of Pharmaceutical SciencesJosai UniversitySakado-shiJapan
  2. 2.Department of Microbiology, Faculty of Pharmaceutical SciencesJosai UniversitySakado-shiJapan

Personalised recommendations