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Improvement of pharmaceutical properties of insulin through conjugation with glucuronylglucosyl-β-cyclodextrin

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Abstract

Recently, a large number of peptides and proteins have been utilized as active pharmaceutical ingredients in the clinical field. However, the stability of peptide and protein drugs is often low. In addition, some peptides and proteins adsorb onto glass or polypropylene tube. In the present study, to improve these pharmaceutical properties of peptides and proteins, we newly prepared glucuronylglucosyl-β-cyclodextrin (GUG-β-CyD) conjugate with insulin, a model protein drug, and evaluated its enzymatic or thermal stability and adsorption onto glass or polypropylene tube. The insulin conjugate with GUG-β-CyD was successfully prepared by condensation of amine group of insulin and carboxyl group of GUG-β-CyD. Circular dichroism spectra showed that the secondary structure of insulin in this conjugate was retained. Adsorption of insulin onto glass or polypropylene tube was decreased by the conjugation with GUG-β-CyD. Moreover, enzymatic and thermal stabilities of the conjugate were higher than those of insulin and the mixture of insulin and GUG-β-CyD. These results suggest that insulin conjugation with GUG-β-CyD could improve the pharmaceutical properties of insulin.

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Acknowledgments

This work was partially supported by a Program for Leading Graduate Schools “HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program”, Kumamoto University, a Grant-in-Aid for Young Scientists (Start-up) from the Ministry of Education, Science and Culture of Japan (23890161) and Kumayaku Rearch Support from KUMAYAKU Alumni Research Foundation.

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Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan

    Tatsunori Hirotsu, Taishi Higashi, Keiichi Motoyama & Hidetoshi Arima

  2. Program for Leading Graduate Schools “HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program”, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan

    Tatsunori Hirotsu & Hidetoshi Arima

  3. Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto, 860-0082, Japan

    Fumitoshi Hirayama

  4. DDS Research Institute, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto, 860-0082, Japan

    Kaneto Uekama

Authors
  1. Tatsunori Hirotsu
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  2. Taishi Higashi
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  3. Keiichi Motoyama
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  4. Fumitoshi Hirayama
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  5. Kaneto Uekama
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  6. Hidetoshi Arima
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Correspondence to Hidetoshi Arima.

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Hirotsu, T., Higashi, T., Motoyama, K. et al. Improvement of pharmaceutical properties of insulin through conjugation with glucuronylglucosyl-β-cyclodextrin. J Incl Phenom Macrocycl Chem 80, 107–112 (2014). https://doi.org/10.1007/s10847-014-0407-5

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  • DOI: https://doi.org/10.1007/s10847-014-0407-5

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