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Liver Targeting of Interferon Through Pullulan Conjugation

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Abstract

Purpose. The purpose of this study was to actively target interferon (IFN) to the liver through its chemical conjugation with pullulan, a water-soluble polysaccharide with a high affinity for the liver.

Methods. Chemical conjugation of IFN with pullulan was achieved by a cyanuric chloride method. Following intravenous injection of the conjugates to mice, their body distribution and the activity of an IFN-induced enzyme, 2′,5′-oligoadenylate (2-5A) synthetase in the liver and other organs, were evaluated.

Results. The cyanuric chloride method enabled us to prepare an IFN-pullulan conjugate that retained approximately 7–↑9 % of the biological activity of IFN. Pullulan conjugation enhanced the liver accumulation of IFN and the retention period with the results being reproducible. When injected intravenously to mice, the IFN-pullulan conjugate enhanced the activity of 2-5A synthetase in the liver. The activity could be induced at IFN doses much lower than those of free IFN injection. In addition, the liver 2-5A synthetase induced by conjugate injection was retained for 3 days, whereas it was lost within the first day for the free IFN-injected mice.

Conclusions. IFN-pullulan conjugation was promising for IFN targeting to the liver with efficient exertion of its antiviral activity therein.

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Author notes

  1. Keli Xi

    Present address: Chemistry Department, Yunnan University, Kunming, 650031, China

Authors and Affiliations

  1. Research Center for Biomedical Engineering, Kyoto University, 53 Kawahara-cho Shogoin, Sakyo-ku, Kyoto, 606, Japan

    Keli Xi & Yasuhiko Tabata

  2. Institut Pastuer de Kyoto, 103-5 Monzen-cho, Tanaka, Sakyo-ku, Kyoto, 606, Japan

    Kazuko Uno, Miwa Yoshimoto, Tsunataro Kishida & Yoshito Ikada

  3. Department of Biotechnology, Kyoto Institute of Technology, Gosyo-kaido-cho, Matsugasaki, Sakyo-ku, Kyoto, 606, Japan

    Yoshihiro Sokawa

Authors
  1. Keli Xi
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  2. Yasuhiko Tabata
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  3. Kazuko Uno
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  4. Miwa Yoshimoto
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  5. Tsunataro Kishida
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  6. Yoshihiro Sokawa
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  7. Yoshito Ikada
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Xi, K., Tabata, Y., Uno, K. et al. Liver Targeting of Interferon Through Pullulan Conjugation. Pharm Res 13, 1846–1850 (1996). https://doi.org/10.1023/A:1016037225728

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  • DOI: https://doi.org/10.1023/A:1016037225728

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