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Intestinal drug delivery systems with biodegradable microspheres targeting mucosal immune-regulating cells for chronic inflammatory colitis

  • Biotherapy and biological response modifiers for IBD
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Abstract

We developed two kinds of delivery systems targeting mucosal immune regulating cells with poly (d,l-lactic acid) microspheres containing dexamethasone and dichloromethylene diphosphonate, and gelatine microspheres containing interleukin-10. To estimate the efficacy of these drug delivery systems, we studied the effects on experimental colitis induced by dextran sodium sulfate, 2,4,6-trinitrobenzene sulfonic acid, and interleukin-10-deficient mice. Intestinal administration of these microspheres significantly improved colitis with decreased histological score, myeloperoxidase activity, and nitric oxide production compared with mice treated with free agents. Gene expressions of tumor necrosis factor-α, interleukin-lβ, and interferon-γ were down-regulated in treated animals. Serum Dx, IL-10 levels, and systemic macrophages were unchanged after treatment. Our findings suggest that local macrophages in the intestine play a critical role in the initiation of chronic colitis in the animal model of inflammatory bowel disease (IBD). Intestinal drug delivery systems with biodegradable microspheres targeting mucosal immune-regulating cells may become a therapeutic approach to human IBD.

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Authors and Affiliations

  1. Division of Gastroenterology and Endoscopic Medicine, Graduate School of Kyoto University, 54 Shogoinkawara-cho, Sakyoku, Kyoto, 606-8507, Japan

    Kazuichi Okazaki, Hiroshi Nakase, Norihiko Watanabe & Tsutomu Chiba

  2. Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan

    Yasuhiko Tabata & Yoshito Ikada

Authors
  1. Kazuichi Okazaki
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  2. Hiroshi Nakase
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  3. Norihiko Watanabe
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  4. Yasuhiko Tabata
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  5. Yoshito Ikada
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  6. Tsutomu Chiba
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Okazaki, K., Nakase, H., Watanabe, N. et al. Intestinal drug delivery systems with biodegradable microspheres targeting mucosal immune-regulating cells for chronic inflammatory colitis. J Gastroenterol 37 (Suppl 14), 44–52 (2002). https://doi.org/10.1007/BF03326413

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