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Isoflavone aglycons-sulfobutyl ether-β-cyclodextrin inclusion complexes: in solution and solid state studies

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Abstract

The effect of a polyanionic variably substituted sulfobutyl ether-β-cyclodextrin (SBE-β-CyD), complexation on the UV absorption of genistein (Gen) and daidzein (Dai) was studied in pure water. A phase solubility study was performed, according to the method reported by Higuchi and Connors, to evaluate the changes of isoflavones in the complexation state and type-AL solubility diagrams for both isoflavones were obtained suggesting that they form complexes with 1:1 molar ratio. These results were confirmed by Job’s plot method. Complexation strongly increases the water solubility of isoflavones. The in vitro dissolution of isoflavones entrapped into SBE-β-CyD significantly surpassed that of the free isoflavones (over 90 % of the loaded Gen and Dai dissolved in 15 and 30 min, respectively). Finally, 1:1 molar ratio solid complexes were prepared by the kneading method and characterized in solid state by FTIR-ATR spectroscopy, with particular regard to O–H and C=O stretching vibrations, achieving structural information on the modifications induced by complexation on the H-bond scheme, also by applying band decomposition and curve-fit.

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References

  1. Reiter, E., Beck, V., Medjakovic, S., Jungbauer, A.: Isoflavones are safe compounds for therapeutical applications-evaluation of in vitro data. Gynecol. Endocrinol. 25, 554–580 (2009)

    Article  CAS  Google Scholar 

  2. Warri, A., Saarinen, N.M., Makela, S., Hilakivi-Clarke, L.: The role of early life genistein exposures in modifying breast cancer risk. Br. J. Cancer 98, 1485–1493 (2008)

    Article  CAS  Google Scholar 

  3. Ratna, W.N.: Inhibition of estrogenic stimulation of gene expression by genistein. Life Sci. 71, 865–877 (2002)

    Article  CAS  Google Scholar 

  4. Mueller, S.O., Simon, S., Chae, K., Metzler, M., Korach, K.S.: Phytoestrogens and their human metabolites show distinct agonistic and antagonistic properties on estrogen receptor alpha (ERalpha) and ERbeta in human cells. Toxicol. Sci. 80, 14–25 (2004)

    Article  CAS  Google Scholar 

  5. Jiang, Q., Payton-Stewart, F., Elliott, S., Driver, J., Rhodes, L.V., Zhang, Q., Zheng, S., Bhatnagar, D., Boue, S.M., Collins-Burow, B.M., Sridhar, J., Stevens, C., McLachlan, J.A., Wiese, T.E., Burow, M.E., Wang, G.: Effects of 7-O substitutions on estrogenic and anti-estrogenic activities of daidzein analogues in MCF-7 breast cancer cells. J. Med. Chem. 53, 6153–6163 (2010)

    Article  CAS  Google Scholar 

  6. Barbosa, A.C., Lajolo, F.M., Genovese, M.I.: Effect of free or protein-associated soy isoflavones on the antioxidant status in rats. J. Sci. Food Agric. 91, 721–731 (2011)

    Article  CAS  Google Scholar 

  7. Byun, J.S., Lee, S.S.: Effect of soybeans and sword beans on bone metabolism in a rat model of osteoporosis. Ann. Nutr. Metab. 56, 106–112 (2010)

    Article  CAS  Google Scholar 

  8. Ruijter, J., Valstar, M.J., Narajczyk, M., Wegrzyn, G., Kulik, W., Ijist, L., Wagemans, T., van der Wal, W.M., Wijburg, F.A.: Genistein in Sanfilippo disease: a randomized controlled crossover tria. Ann. Neurol. 71, 110–120 (2012)

    Article  Google Scholar 

  9. Uckun, F.M., Evans, W.E., Forsyth, C.J., Waddick, K.G., Ahlgren, L.T., Chelstrom, L.M., Burkhardt, A., Bolen, J., Myers, D.E.: Biotherapy of B-cell precursor leukemia by targeting genistein to CD19-associated tyrosine kinases. Science 267, 886–891 (1995)

    Article  CAS  Google Scholar 

  10. Rusin, A., Krawczyk, Z., Grynkiewicz, G., Gogler, A., Zawisza-Puchałka, J., Szeja, W.: Synthetic derivatives of genistein, their properties and possible applications. Acta Biochim. Pol. 57, 23–34 (2010)

    CAS  Google Scholar 

  11. Si, H.Y., Li, D.P., Wang, T.M., et al.: Improving the anti-tumor effect of genistein with a biocompatible superparamagnetic drug delivery system. J. Nanosci. Nanotechnol. 10, 2325–2331 (2010)

    Article  CAS  Google Scholar 

  12. Zhang, Z.W., Huang, Y., Gao, F., Bu, H.H., Gu, W.W., Li, Y.P.: Daidzein-phospholipid complex loaded lipid nanocarriers improved oral absorption: in vitro characteristics and in vivo behaviour in rats. Nanoscale 3, 1780–1787 (2011)

    Article  CAS  Google Scholar 

  13. Loftsson, T., Brewster, M.E.: Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J. Pharm. Sci. 85, 1017–1025 (1996)

    Article  CAS  Google Scholar 

  14. Loftsson, T., Brewster, M.E.: Pharmaceutical applications of cyclodextrins: basic science and product development. J. Pharm. Pharmacol. 62, 1607–1621 (2010)

    Article  CAS  Google Scholar 

  15. Tolman, J.A., Nelson, N.A., Son, Y.J., Bosselmann, S., Wiederhold, N.P., Peters, J.I., McConville, J.T., Williams III, R.O.: Characterization and pharmacokinetic analysis of aerosolized aqueous voriconazole solution. Eur. J. Pharm. Biopharm. 72, 199–205 (2009)

    Article  CAS  Google Scholar 

  16. Savolainen, J., Järvinen, K., Matilainen, L., Järvinen, T.: Improved dissolution and bioavailability of phenytoin by sulfobutylether-β-cyclodextrin (SBE)7 M-β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) complexation. Int. J. Pharm. 165, 69–78 (1998)

    Article  CAS  Google Scholar 

  17. García-Río, L., Méndez, M., Paleo, M.R., Sardina, F.J.: New insights in cyclodextrin: surfactant mixed systems from the use of neutral and anionic cyclodextrin derivatives. J. Phys. Chem. B 111, 12756–12764 (2007)

    Article  Google Scholar 

  18. Lockwood, S.F., O’Malley, S., Mosher, G.L.: Improved aqueous solubility of crystalline astaxanthin (3,30-dihydroxy-b, β-carotene-4,40-dione) by Captisol® (sulfobutyl ether β-cyclodextrin). J. Pharm. Sci. 92, 922–926 (2003)

    Article  CAS  Google Scholar 

  19. Fukuda, M., Miller, D.A., Peppas, N.A., McGinity, J.W.: Influence of sulfobutyl ether-β-cyclodextrin (Captisol®) on the dissolution properties of a poorly soluble drug from extrudates prepared by hot-melt extrusion. Int. J. Pharm. 350, 188–196 (2008)

    Article  CAS  Google Scholar 

  20. Qu, Q., Tucker, E., Christian, S.D.: Sulfoalkyl ether β-cyclodextrin derivatives: synthesis and characterizations. J. Incl. Phenom. Macrocycl. Chem. 43, 213–221 (2002)

    Article  CAS  Google Scholar 

  21. Sotthivira, S., Haslam, J.L., Stella, V.J.: Evaluation of various properties of alternative salt forms of sulfobutylether-β-cyclodextrin, (SBE)7 M-β-CD. Int. J. Pharm. 330, 73–81 (2007)

    Article  Google Scholar 

  22. Song, A.J., Wang, J.H., Liu, C.D., Deng, L.H.: Sulfoalkyl ether β-cyclodextrin derivatives synthesized by a single step method as pharmaceutical biomaterials. Chin. Sci. Bull. 54, 3187–3199 (2009)

    Article  CAS  Google Scholar 

  23. Loftsson, T., Magnusdottir, A., Masson, M., Sigurjonsdottir, J.F.: Self-association and cyclodextrin solubilization of drugs. J. Pharm. Sci. 91, 2307–2316 (2002)

    Article  CAS  Google Scholar 

  24. Loftsson, T., Masson, M., Brewster, M.E.: Self-association of cyclodextrin and cyclodextrin complexes. J. Pharm. Sci. 93, 1091–1099 (2004)

    Article  CAS  Google Scholar 

  25. Stella, V.J., He, Q.: Cyclodextrins. Toxicol. Pathol. 36, 30–42 (2008)

    Article  CAS  Google Scholar 

  26. Messner, M., Kurkov, S.V., Jansook, P., Loftsson, T.: Selfassembled cyclodextrin aggregates and nanoparticles. Int. J. Pharm. 387, 199–208 (2010)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  29. Rajewski, R.A., Traiger, G., Bresnahan, J., Jaberaboansri, P., Stella, V.J., Thompson, D.O.: Preliminary safety evaluation of parenterally administrated sulfoalkyl ether β-cyclodextrin derivatives. J. Pharm. Sci. 84, 927–932 (1995)

    Article  CAS  Google Scholar 

  30. Sotthivirat, S., Haslam, J.L., Stella, V.J.: Evaluation of various properties of alternative salt forms of sulfobutylether-β-cyclodextrin, (SBE)7 M-β-CD. Int. J. Pharm. 330, 73–81 (2007)

    Article  CAS  Google Scholar 

  31. Xiao, D., Yang, B., Zhao, Y.L., Liao, X.L., Yang, X.M., Wang, F., Chen, Y.J., Zhou, R.G.: Inclusion complexes of dihydroartemisinin with cyclodextrin and its derivatives: characterization, solubilization and inclusion mode. J. Incl. Phenom. Macrocycl. Chem. 79, 349–356 (2014)

    Article  CAS  Google Scholar 

  32. Cannavà, C., Crupi, V., Guardo, M., Majolino, D., Stancanelli, R., Tommasini, S., Ventura, C.A., Venuti, V.: Phase solubility and FTIR-ATR studies of idebenone/sulfobutyl ether β-cyclodextrin inclusion complex. J. Incl. Phenom. Macrocycl. Chem. 75, 255–262 (2013)

    Article  Google Scholar 

  33. Crupi, V., Ficarra, R., Guardo, M., Majolino, D., Stancanelli, R., Venuti, V.: UV–Vis and FTIR-ATR spectroscopic techniques to study the inclusion complexes of genistein with β-cyclodextrins. J. Pharm. Biomed. Anal. 44, 110–117 (2007)

    Article  CAS  Google Scholar 

  34. Stancanelli, R., Mazzaglia, A., Tommasini, S., Calabrò, M.L., Guardo, M., Villari, V., Ficarra, P., Ficarra, R.: The enhancement of isoflavones water solubility by complexation with modified cyclodextrins: a spectroscopic investigation with implications in the pharmaceutical analysis. J. Pharm. Biomed. Anal. 44, 980–984 (2007)

    Article  CAS  Google Scholar 

  35. Cannavà, C., Crupi, V., Ficarra, P., Guardo, M., Majolino, D., Stancanelli, R., Venuti, V.: Physicochemical characterization of coumestrol/β-cyclodextrins inclusion complexes by UV–Vis and FTIR-ATR spectroscopies. Vib. Spectrosc. 48, 172–178 (2008)

    Article  Google Scholar 

  36. Crupi, V., Majolino, D., Paciaroni, A., Stancanelli, R., Venuti, V.: Influence of the “host-guest” interactions on the mobility of genistein/β-cyclodextrin inclusion complex. J. Phys. Chem. B 113, 11032–11038 (2009)

    Article  CAS  Google Scholar 

  37. Cannavà, C., Crupi, V., Ficarra, P., Guardo, M., Majolino, D., Mazzaglia, A., Stancanelli, R., Venuti, V.: Physico-chemical characterization of an amphiphilic cyclodextrin/genistein complex. J. Pharm. Biomed. Anal. 51, 1064–1068 (2010)

    Article  Google Scholar 

  38. Crupi, V., Majolino, D., Paciaroni, A., Rossi, B., Stancanelli, R., Venuti, V., Viliani, G.: The effect of hydrogen bond on the vibrational dynamics of genistein free and complexed with β-cyclodextrins. J. Raman Spectrosc. 41, 764–770 (2010)

    CAS  Google Scholar 

  39. Daruhazi, A.E., Szente, L., Balogh, B., Matyus, P., Beni, S., Takacs, M., et al.: Utility of cyclodextrins in the formulation of genistein: Part 1. Preparation and physicochemical properties of genistein complexes with native cyclodextrins. J. Pharm. Biomed. Anal. 48, 636–640 (2008)

    Article  CAS  Google Scholar 

  40. Xavier, C.R., Silva, A.P.C., Schwingel, L.C., Borghetti, G.S., Koester, L.S., Mayorga, P., Teixeira, H.F., Bassani, V.L., Lula, I.S., Sinisterra, R.D.: Improvement of genistein content in solid genistein/β-cyclodextrin complexes. Quim. Nova 33, 587–590 (2010)

    Article  CAS  Google Scholar 

  41. Higuchi, T., Connors, K.A.: Phase-solubility techniques. Adv. Anal. Chem. Instrum. 4, 117–212 (1965)

    CAS  Google Scholar 

  42. Gibaud, S., Zirar, S.B., Mutzenhardt, P., Fries, I., Astier, A.: Melarsoprol-cyclodextrins inclusion complexes. Int. J. Pharm. 306, 107–121 (2005)

    Article  CAS  Google Scholar 

  43. Crupi, V., Longo, F., Majolino, D., Venuti, V.: Vibrational properties of water molecules adsorbed in different zeolitic frameworks. J. Phys. 18, 3563–3580 (2006)

    CAS  Google Scholar 

  44. Brewster, M.E., Loftsson, T.: Cyclodextrins as pharmaceutical solubilizers. Adv. Drug Deliv. Rev. 59, 645–666 (2007)

    Article  CAS  Google Scholar 

  45. Loftsson, T., Hreinsdóttir, D., Másson, M.: Evaluation of cyclodextrin solubilization of drugs. Int. J. Pharm. 302, 18–28 (2005)

    Article  CAS  Google Scholar 

  46. Singh, H., Singh, S., Srivastava, A., Tandon, P., Bharti, P., Kumar, S., Maurya, R.: Conformational analysis and vibrational study of daidzein by using FT-IR and FT-Raman spectroscopies and DFT calculations. Spectrochim. Acta Part A 120, 405–415 (2014)

    Article  CAS  Google Scholar 

  47. Li, N., Liu, J., Zhao, X., Gao, Y., Zhang, L., Zhang, J., Yu, L.: Complex formation of ionic liquid surfactant and β-cyclodextrin. Colloids Surf. A 292, 196–201 (2007)

    Article  CAS  Google Scholar 

  48. Hamidi, H., Abderrahim, R., Meganem, F.: Spectroscopic studies of inclusion complex of β-cyclodextrin and benzidine diammonium dipicrate, Spectrochim. Acta Part A: Mol. Biomol. Spectrosc. 75, 32–36 (2010)

    Article  Google Scholar 

  49. Gavira, J.M., Hernanz, A., Bratu, I.: Dehydration of β-cyclodextrin: an IR ν(OH) band profile analysis. Vib. Spectrosc. 32, 137–146 (2003)

    Article  CAS  Google Scholar 

  50. Stancanelli, R., Ficarra, R., Cannavà, C., Guardo, M., Calabrò, M.L., Ficarra, P., Ottanà, R., Maccari, R., Crupi, V., Majolino, D., Venuti, V.: UV–Vis and FTIR-ATR characterization of 9-fluorenon-2-carboxyester/(2-hydroxypropyl)-β-cyclodextrin inclusion complex. J. Pharm. Biomed. Anal. 47, 704–709 (2008)

    Article  CAS  Google Scholar 

  51. Bratu, I., Veiga, F., Fernandes, C., Hernanz, A., Gavira, J.M.: Infrared spectroscopic study of triacetyl-β-cyclodextrin and its inclusion complex with nicapiridine. Spectroscopy 18, 459–467 (2004)

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Dipartimento di Scienze del Farmaco e Prodotti per la Salute, Università di Messina, V.le Annunziata, 98168, Messina, Italy

    Rosanna Stancanelli, A. Arigò, M. L. Calabrò, S. Tommasini & C. A. Ventura

  2. Dipartimento di Fisica e di Scienze della Terra, Università di Messina, Viale F. Stagno D’Alcontres 31, 98166, Messina, Italy

    Valentina Venuti, V. Crupi & D. Majolino

  3. Dipartimento di Patologia Umana, Università di Messina, Via Consolare Valeria, 1, Policlinico Universitario, Pad.H, 98125, Messina, Italy

    C. Cannavà

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  1. Rosanna Stancanelli
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  2. Valentina Venuti
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  3. A. Arigò
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  4. M. L. Calabrò
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  5. C. Cannavà
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  6. V. Crupi
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  7. D. Majolino
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Correspondence to Rosanna Stancanelli or Valentina Venuti.

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Stancanelli, R., Venuti, V., Arigò, A. et al. Isoflavone aglycons-sulfobutyl ether-β-cyclodextrin inclusion complexes: in solution and solid state studies. J Incl Phenom Macrocycl Chem 83, 27–36 (2015). https://doi.org/10.1007/s10847-015-0535-6

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  • DOI: https://doi.org/10.1007/s10847-015-0535-6

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