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AAPS PharmSciTech

, Volume 19, Issue 7, pp 3048–3056 | Cite as

Characterization of Inclusion Complex of Coenzyme Q10 with the New Carrier CD-MOF-1 Prepared by Solvent Evaporation

  • Yutaka Inoue
  • Ayumi Nanri
  • Isamu Murata
  • Ikuo Kanamoto
Research Article
  • 164 Downloads

Abstract

The aim of the current study was to evaluate the physicochemical properties of a solid dispersion of coenzyme Q10 (CoQ10)/cyclodextrin metal organic frameworks-1 (CD-MOF-1). As a result of the powder X-ray diffraction (PXRD), it was confirmed that the CD-MOF-1 was changed from the α form to the β form by evaporation (EVP). A diffraction peak due to melting of CoQ10 disappeared the EVP (CoQ10/CD-MOF-1 = 1/2). The structure of this complex is presumed to be similar to the β form of CD-MOF-1. As a result of the differential scanning calorimetry (DSC), the endothermic peak due to the melting of CoQ10 disappeared the EVP (CoQ10/CD-MOF-1 = 1/2). As a result of the near-infrared (NIR) absorption spectroscopy, findings suggested the hydrogen bond in formation between the CH group in the isoprene side chains of CoQ10 and the OH group of CD-MOF-1. Therefore, the formation of crystal solid dispersion in CoQ10/CD-MOF-1 was suggested. As a result of the dissolution test in distilled water, the EVP (CoQ10/CD-MOF-1 = 1/2) had better dissolution in comparison to CoQ10 alone. Furthermore, also in fasted state simulated intestinal fluid (FaSSIF) in vivo, the EVP (CoQ10/CD-MOF-1 = 1/2) had better dissolution in the human body than CoQ10 alone. From the results of 2D-nuclear overhauser effect spectroscopy (NOESY) NMR spectroscopy, CD-MOF-1 could not include the benzoquinone ring of CoQ10. It was confirmed that the isoprene side chain was included. Therefore, it was suggested that CD-MOF-1 useful as a novel drug carrier for CoQ10.

KEY WORDS

coenzyme Q10 cyclodextrin metal organic frameworks-1 inclusion complex evaporation 

Notes

Acknowledgements

The authors wish to sincerely thank CycloChemBio, which provided γCD, CoQ10, and CoQ10W that were used in this study, and Büchi Labortechnik AG, which provided advice regarding infrared spectroscopy.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Mason JA, Veenstrab M, Long JR. Evaluating metal–organic frameworks for natural gas storage. Chem Sci. 2014;5(1):32–51.CrossRefGoogle Scholar
  2. 2.
    Ma S, Zhou SC. Gas storage in porous metal-organic frameworks for clean energy applications. Chem Commun. 2010;46:44–53.CrossRefGoogle Scholar
  3. 3.
    Li B, Wen HM, Zhou W, Chen B. Porous metal-organic frameworks for gas storage and separation: what, how, and why? J Phys Chem Lett. 2014;20:3468–79.CrossRefGoogle Scholar
  4. 4.
    Chen B, Xiang S, Qian G. Metal-organic frameworks with functional pores for recognition of small molecules. Acc Chem Res. 2010;43:1115–24.CrossRefGoogle Scholar
  5. 5.
    Li JR, Sculley J, Zhou HC. Metal-organic frameworks for separations. Chem Rev. 2012;112:869–932.CrossRefGoogle Scholar
  6. 6.
    Horcajada P, Gref R, Baati T, Allan PK, Maurin G, Couvreur P, et al. Metal-organic frameworks in biomedicine. Chem Rev. 2012;112(2):1232–68.CrossRefGoogle Scholar
  7. 7.
    Smaldone RA, Forgan RS, Furukawa H, Gassensmith JJ, Slawin AMZ, Yaghi OM, et al. Metalorganic frameworks from edible natural products. Angew Chemie Int Ed. 2010;49(46):8630–4.CrossRefGoogle Scholar
  8. 8.
    Hartlieb KJ, Holcroft JM, Moghadam PZ, Vermeulen NA, Algaradah MM, Nassar MS, et al. CD-MOF: a versatile separation medium. J Am Chem Soc. 2016;138:2292–301.CrossRefGoogle Scholar
  9. 9.
    Graham AJ, Allan DR, Muszkiewicz A, Morrison CA, Moggach SA. The effect of high pressure on MOF-5: guest-induced modification of pore size and content at high pressure. Angew Chem Int Ed. 2011;50:11138–41.CrossRefGoogle Scholar
  10. 10.
    Patyk-Kaźmierczak E, Warren MR, Allan DR, Katrusiak A. Pressure inverse solubility and polymorphism of an edible γ-cyclodextrin-based metal–organic framework. Phys Chem Chem Phys. 2017;19(13):9086–91.CrossRefGoogle Scholar
  11. 11.
    Liu J, Bao T-Y, Yang X-Y, Zhu P-P, Wu L-H, Sha J-Q, et al. Controllable porosity conversion of metal-organic frameworks composed of natural ingredients for drug delivery. Chem Commun. 2017;53(55):7804–7.CrossRefGoogle Scholar
  12. 12.
    Ernster L, Dallner G. Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta. 1995;1271:195–204.CrossRefGoogle Scholar
  13. 13.
    Bhagavan HN, Chopra RK. Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006;40:445–53.CrossRefGoogle Scholar
  14. 14.
    Thomas SR, Witting PK, Stocker R. A role for reduced coenzyme Q in atherosclerosis? Biofactors. 1999;9:207–24.CrossRefGoogle Scholar
  15. 15.
    Bank G, Kagan D, Madhavi D. Coenzyme Q10: clinical update and bioavailability. J Evid Based Complement Alternat Med. 2011;16(1):129–37.CrossRefGoogle Scholar
  16. 16.
    Uekaji Y, Terao K. Coenzyme Q10-gamma cyclodextrin complex is a powerful nutraceutical for anti-aging and health improvements. Biomed Res Clin Pract. 2017;2(1)  https://doi.org/10.15761/BRCP.1000125.
  17. 17.
    Bliznakov EG, Wilkins DJ. Biochemical and clinical consequences of inhibiting coenzyme Q10 biosynthesis by lipid-lowering HMG-CoA reductase inhibitors (statins): a critical overview. Adv Ther. 1998;5:218–28.Google Scholar
  18. 18.
    Crane F, Hatefi Y, Lester RL, Widmer C. Isolation of a quinone from beef heart mitochondria. Biochem Biophys Acta. 1957;25:220–1.CrossRefGoogle Scholar
  19. 19.
    Overvad K, Diamant B, Holm L, Holmer G, Mortensen SA, Stender S. Coenzyme Q10 in health and disease. Eur J Clin Nutr. 1999;53:764–70.CrossRefGoogle Scholar
  20. 20.
    Sarter B. Coenzyme Q10 and cardiovascular disease: a review. J Cardiovasc Nurs. 2002;116:9–20.CrossRefGoogle Scholar
  21. 21.
    Greenberg S, Frishman WH. Coenzyme Q10: a new drug for cardiovascular disease. J Clin Pharmacol. 1990;30:590–608.CrossRefGoogle Scholar
  22. 22.
    Miyamoto S, Kawai A, Higuchi S, Nishi Y, Tanimoto T, Uekaji Y, et al. Structural studies of coenzyme Q10 inclusion complex with gamma-cyclodextrin using chemical analyses and molecular modeling. Chem-Bio Inf J. 2009;9:1–11.Google Scholar
  23. 23.
    Li X, Guo T, Lachmanski L, Manoli F, Menendez-Miranda M, Manet I, et al. Cyclodextrin-based metal-organic frameworks particles as efficient carriers for lansoprazole: study of morphology and chemical composition of individual particles. Int J Pharm. 2017;531(2):424–32.CrossRefGoogle Scholar
  24. 24.
    Lv N, Guo T, Liu B, Wang C, Singh V, Xu X, et al. Improvement in thermal stability of sucralose by γ-cyclodextrin metal-organic frameworks. Pharm Res. 2017;34(2):269–78.CrossRefGoogle Scholar
  25. 25.
    Gao X, Nishimura K, Hirayama F, Arima H, Uekama K, Schmid G, et al. Enhanced dissolution and oral bioavailability of coenzyme Q10 in dogs obtained by inclusion complexation with γ-cyclodextrin. Asian J Pharm Sci. 2006;1(2):95–102.Google Scholar
  26. 26.
    Vertzoni M, Fotaki N, Nicolaides E, Reppas C, Kostewicz E, Stippler E, et al. Dissolution media simulating the intralumenal composition of the small intestine: physiological issues and practical aspects. J Pharm Pharmacol. 2004;56(4):453–62.CrossRefGoogle Scholar
  27. 27.
    Uekaji Y, Jo A, Ohnishi M, Nakata D, Terao K. A new generation of nutra-ceuticals and cosme-ceuticals complexing lipophilic bioactives with γ-cyclodextrin. Procedia Eng. 2012;36:540–50.CrossRefGoogle Scholar
  28. 28.
    Kwon SS, Nam YS, Lee JS, Ku BS, Han SH, Lee JY, et al. Preparation and characterization of coenzyme Q 10-loaded PMMA nanoparticles by a new emulsification process based on microfluidization. Colloids Surf A Physicochem Eng Asp. 2002;210:95–104.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  1. 1.Laboratory of Drug Safety Management, Faculty of Pharmacy and Pharmaceutical SciencesJosai UniversitySaitamaJapan

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