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β-Cyclodextrins bearing ethylene glycol chains at their primary side: their preparations and evaluation as solubilizing agents for 17-β-estradiol and nuclear magnetic resonance structural analysis of a 17-β-estradiol inclusion complex

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Abstract

In this study, we designed and prepared two new β-cyclodextrins (1 and 2) bearing ethylene glycol chains to develop highly water-soluble cyclodextrins. They had excellent water solubility and could successfully dissolve 17-β-estradiol in water, which was considered a poorly soluble drug model. Additionally, the nuclear magnetic resonance structural analysis of a mixed sample of 17-β-estradiol and 1 in D2O–H2O suggested two different types of inclusion complexes with different 17-β-estradiol molecule orientations inside the cavity of 1.

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Abbreviations

CyD:

Cyclodextrin

TEG:

Tetra(Ethylene) Glycol

OEG:

Octa(Ethylene) Glycol

E2:

17-β-Estradiol

G1-β-CyD:

6-O-α-D-Glucosyl-β-CyD

References

  1. Szejtli, J.: Introduction and general overview of cyclodextrin chemistry. Chem. Rev. 98, 1743–1754 (1998)

    Article  CAS  PubMed  Google Scholar 

  2. Das, S.K., Rajabalaya, R., David, S., Gani, N., Khanam, J., Nanda, A.: Cyclodextrins-the molecular container. Res. J. Pharm. Biol. Chem. Sci. 4, 1694–1720 (2013)

    CAS  Google Scholar 

  3. Maazaoui, R., Abderrahim, R.: Applications of cyclodextrins: formation of inclusion complexes and their characterization. Int. J. Adv. Res. 3, 757–781 (2015)

    Google Scholar 

  4. Loftsson, T., Jarho, P., Másson, M., Järvinen, T.: Cyclodextrins in drug delivery. Expert Opin. Drug Deliv. 2, 335–351 (2005)

    Article  CAS  PubMed  Google Scholar 

  5. Uekama, K.: Design and evaluation of cyclodextrin-based drug formulation. Chem. Pharm. Bull. 52, 900–915 (2004)

    Article  CAS  Google Scholar 

  6. Szente, L., Szejtli, J.: Highly soluble cyclodextrin derivatives: chemistry, properties, and trends in development. Adv. Drug Deliv. Rev. 36, 17–28 (1999)

    Article  CAS  PubMed  Google Scholar 

  7. Goswami, L.N., Houston, Z.H., Sarma, S.J., Jalisatgi, S.S., Hawthorne, M.F.: Efficient synthesis of diverse heterobifunctionalized clickable oligo(ethylene glycol) linkers: potential applications in bioconjugation and targeted drug delivery. Org. Biomol. Chem. 11, 1116–1126 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bonandi, E., Christodoulou, M.S., Fumagalli, G., Perdicchia, D., Rastelli, G., Passarella, D.: The 1,2,3-triazole ring as a bioisostere in medicinal chemistry. Drug Discov. Today 22, 1572–1581 (2017)

    Article  CAS  PubMed  Google Scholar 

  9. Yilmaz, V.T., Kazak, C., Ağar, E., Kahveci, B., Guven, K.: Three 1,2,4-triazole derivatives containing substituted benzyl and benzylamino groups. Acta Crystallogr. C 61, o101–o104 (2005)

    Article  PubMed  Google Scholar 

  10. Sahin, O., Büyükgüngör, O., Saşmaz, S., Gümrükçüoğlu, N., Kantar, C.: N-H...N and C-H...pi interactions in 4-amino-3-methyl-5-(p-tolyl)-4H-1,2,4-triazole and 4-amino-3-methyl-5-phenyl-4H-1,2,4-triazole. Acta Crystallogr. C. 62, o643–o646 (2006)

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  12. Mazurek, A.H., Szeleszczuk, Ł, Bethanis, K., Christoforides, E., Dudek, M.K., Zielinska-Pisklak, M., Pisklak, D.M.: 17-β-Estradiol-β-cyclodextrin complex as solid: synthesis, structural and physicochemical characterization. Molecules 28, 3747 (2023)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Vicatos, A.I., Hoossen, Z., Caira, M.R.: Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements. Beilstein J. Org. Chem. 18, 1749–1762 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sadlej-Sosnowska, N.: Influence of the structure of steroid hormones on their association with cyclodextrins: a high-performance liquid chromatography study. J. Incl. Phenom. Macro. Chem. 27, 31–40 (1997)

    Article  CAS  Google Scholar 

  15. Yañez, C., Basualdo, J., Jara-Ulloa, P., Squella, J.A.: Inclusion complexes of estrone and estradiol with β-cyclodextrin: voltammetric and HPLC studies. J. Phys. Org. Chem. 20, 499–505 (2007)

    Article  Google Scholar 

  16. Yañez, C., Basquinzay, R.: Chronocoulometry diffusion coefficients as a measure of cyclodextrin-estradiol complex association. J. Electroanal. Chem. 622, 242–245 (2008)

    Article  Google Scholar 

  17. Cutrone, G., Li, X., Casas-Solvas, J.M., Menendez-Miranda, M., Qiu, J., Benkovics, G., Constantin, D., Malanga, M., Moreira-Alvarez, B., Costa-Fernandez, J.M., García-Fuentes, L., Gref, R., Vargas-Berenguel, A.: Design of engineered cyclodextrin derivatives for spontaneous coating of highly porous metal-organic framework nanoparticles in aqueous media. Nanomaterials 9, 1103 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Boger, J., Corcoran, R., Lehn, J.: Cyclodextrin chemistry. selective modification of all primary hydroxyl groups of α- and β-cyclodextrins. Helv. Chim. Acta. 61, 2190–2218 (1978)

    Article  CAS  Google Scholar 

  19. Chatjigakis, A.K., Donzé, C., Coleman, A.W.: Solubility behavior of β-cyclodextrin in water/cosolvent mixtures. Anal. Chem. 64, 1632–1634 (1992)

    Article  CAS  Google Scholar 

  20. Okada, Y., Matsuda, K., Hara, K., Hamayasu, K., Hashimoto, H., Koizumi, K.: Properties and the inclusion behavior of 6-O-α-D-Galactosyl- and 6-O-α-D-Mannosyl-cyclodextrins. Chem. Pharm. Bull. 47, 1564–1568 (1999)

    Article  CAS  Google Scholar 

  21. Commodari, F., Sclavos, G., Ibrahimi, S., Khiat, A., Boulanger, Y.: Comparison of 17-β-estradiol structures from x-ray diffraction and solution NMR. Magn. Reson. Chem. 43, 444–450 (2005)

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Technology Joint Management Office, Tokai University, 4-1-1 Kitakaname, Hiratsuka, Kanagawa, 259-1292, Japan

    Yoshiki Oda

  2. Department of Chemistry, School of Science, Tokai University, 4-1-1 Kitakaname, Hiratsuka, Kanagawa, 259-1292, Japan

    Junki Nakagawa

  3. Department of Human Ecology, Wayo Women’s University, Chiba, 272-8533, Japan

    Kaname Kasturaya

  4. Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan

    Takashi Yamanoi

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  1. Yoshiki Oda
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  2. Junki Nakagawa
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  3. Kaname Kasturaya
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  4. Takashi Yamanoi
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Contributions

Yosihiki Oda: preparation of manuscript Junki Nakagawa: compound synthesis Kaname Kasturaya: modeling Takashi Yamanoi: research idea

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Correspondence to Yoshiki Oda or Takashi Yamanoi.

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Oda, Y., Nakagawa, J., Kasturaya, K. et al. β-Cyclodextrins bearing ethylene glycol chains at their primary side: their preparations and evaluation as solubilizing agents for 17-β-estradiol and nuclear magnetic resonance structural analysis of a 17-β-estradiol inclusion complex. J Incl Phenom Macrocycl Chem 103, 421–428 (2023). https://doi.org/10.1007/s10847-023-01206-0

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  • DOI: https://doi.org/10.1007/s10847-023-01206-0

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