Development of new drug delivery system with microcapsules containing FK506 for treatment of patients with ulcerative colitis.

• Project/Area Number: 14570464
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: KYOTO UNIVERSITY
• Principal Investigator: YAZUMI Syujiro (2003) Kyoto University, Department of Gastroenterology and Hepatology, Assistant professor, 医学研究科, 助手 (60332722); 河南 智晴 (2002) 京都大学, 医学研究科, 助手 (30293864)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥2,300,000 (Direct Cost: ¥2,300,000); Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: drug delivery system / microcapsules / FK506 / ulserative colitis / Crohn's disease

Research Abstract

We developed the drug delivery system with microcapsules targeting gastrointestinal lymphoid tissues, which play an important role in mucosal immune-response, for getting more therapeutic efficacy of immuno modulators with avoiding the side effects.
In this study, we have successfully incorporated FK506 into these microcapsules (FK506 microcapsules). And the therapeutic and pharmacokinetic effects of oral administration of FK506 microcapsules on dextran sulfate sodium (DSS)-induced coltis and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis were examined.
(Results) No significant elevation of FK506 in plasma was observed after administration of FK506 microcapsules. Histological score is significantly lower in the groups treated with FK506 microcapsules (FK506-MS) than in non-treated group. Compared to non-treated group, MPO activity and NO production of colonic tissue were significantly decreased in the groups treated with FK506-MS as well as the expression of proinflammatory cytokines. Moreover, transcriptional factor, T-bet and NF-kappa B expression, which are mainly involved in expressions of Th1 cytokines, were decreased in the group treated with FK506-MS. These results suggested that treatment with FK506-MS might have a potent effect on improving experimental colitis without systemic adverse effects. Now, we have already started to investigate the effect of FK506-MS on interleukin-10 knock out mice, which mostly resemble human Crohn's disease.

Research Products

• [Publications] Nakase H, Okazaki K, et al.: "The possible involvement of micro-organisms other than Helicobacter pylori in the development of rectal MALT lymphoma in H. pylori-negative patients."Endoscopy. 34(4). 343-346 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Jeffers M, Nakase H, et al.: "A novel human fibroblast growth factor treats experimental intestinal inflammation."Gastroenterology. 123(4). 1151-1162 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nakase H, Okazaki K, et al.: "Biodegradable microspheres targeting mucosal immune-regulating cells : new approach for treatment of inflammatory bowel disease."J Gastroenterol.. Suppl 15. 59-62 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nakase H, Okazaki K, et al.: "Hepatobiliary and pancreatic : Primary rabdomyosarcoma of the liver."J Gastroenterol Hepatol.. 18(1). 105 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hisatsune Y, Yazumi S, et al.: "Endoscopic management of biliary strictures after duct-to-duct biliary reconstruction in right-lobe living-donor liver transplantation."Transplantation. 76(5). 810-815 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Wada M, Yazumi S, et al.: "Frequent loss of RUNX3 gene expression in human bile duct and pancreatic cancer cell lines."Oncogene. 23(13). 2401-2407 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nakase H, Okazaki K, Ohana M, Ikeda K, Uchida K, Uose S, Itoh T, Iwano M, Watanabe N, Yazumi S, Kawanami C, Inoue F, Chiba T: "The possible involvement of micro-organisms other than Helicobacter pylon in the development of rectal MALT lymphoma in H. pylon-negative patients."Endoscopy. 34(4). 343-346 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Jeffens M, McDonald WF, Chillakuru RA, Yang M, Nakase H, Deegler LL, Sylander ED, Rittman B, Bendele A, Sartor RB, Lichenstein HS: "A novel human fibroblast growth factor treats experimental intestinal inflammation."Gastroenterology. 123(4). 1151-1162 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nakase H, Okazaki K, Tabata Y, Chiba T: "Biodegradable microspheres targeting mucosal immune-regulating cells: new approach for treatment of inflammatory bowel disease."J Gastroenterol. 15. 59-62 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nakase H, Okazaki K, Matsuura M, Chiba T: "Hepatobiliary and pancreatic: Primary rabdomyosarcoma of the liver."J Gastroenterol Hepatol. 18(1). 105 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hisatsune H, Yazumi S, Egawa H, Asada M, Hasegawa K, Kodama Y, Okazaki K, Itoh K, Takakuwa H, Tanaka K, Chiba T: "Endoscopic management of biliany strictures after duct-to-duct biliary reconstruction in right-lobe living-donor liver transplantation."Transplantation. 15;76(5). 810-815 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Wada M, Yazumi S, Takaishi S, Hasegawa K, Sawada M, Tanaka H, Ida H, Sakakuna C, Ito K, Ito Y, Chiba T: "Frequent loss of RUNX3 gene expression in human bile duct and pancreatic cancer cell lines."Oncogene. 23(13). 2401-2407 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hisatsune Y, Yazumi S, et al.: "Endoscopic management of biliary strictures after duct-to-duct biliary reconstruction in right-lobe living-donor liver transplantation"Transplantation. 76. 810-815 (2003)
• [Publications] Wada M, Yazumi S, et al.: "Frequent hypermethylation of RUNX3 gene in human biliary and pancreatic cancer cells"Oncogene. (in press). (2004)
• [Publications] Nakase H, Okazaki K, et al.: "The possible involvement of micro-organisms other than Helicobacter pylori in the development of rectal MALT lymphoma in H. pylori-negative patients"Endoscopy. 34(4). 343-346 (2002)
• [Publications] Jeffers M, Nakase H, et al.: "A novel human fibroblast growth factor treats experimental intestinal inflammation"Gastroenterology. 123(4). 1151-1162 (2002)
• [Publications] Nakase H, Okazaki K, et al.: "Biodegradable microspheres targeting mucosal immune-regulating cells : new approach for treatment of inflammatory bowel disease"J Gastroenterol.. Suppl 15. 59-62 (2003)
• [Publications] Nakase H, Okazaki K, et al.: "Hepatobiliary and pancreatic : Primary rabdomyosarcoma of the liver"J Gastroenterol Hepatol.. 18(1). 105 (2003)
• [Publications] Maisushima Y, Kawanami C, et al.: "Immunological and molecular analysis of B lymphocytes in low-grade MALT lymphoma of the stomach. -Are there any useful markers for predicting outcome after Helicobacter pylori eradication? -"J Gastroenterol. 37. 428-433 (2002)
• [Publications] Nakase H, Kawanami C, et al.: "Rectal leiomyoma with fibromuscular obliteration mimicking adenomatous lesion"Endoscopy. 34. 241 (2002)
• [Publications] Watanabe N, Kawanami C, et al.: "Regression of fundic gland polyps following acquisition of helicobacter pylori"Gut. 51. 742-745 (2002)
• [Publications] Nakase H, Kawanami C, et al.: "New cytokine delivery system using gelatin microspheres containing interleukin-1O for experimental inflammatory bowel disease"J Pharmacol Exp Ther. 301. 59-65 (2002)
• [Publications] Nakase H, Kawanami C, et al.: "Diffuse type of colon cancer with tumor thrombus in the portal vein"Gastrointest Endosc. 55. 239-240 (2002)
• [Publications] Nakase H, Kawanami C, et al.: "The possible involvement of microorganisms, other than Helicobacter pylori in the development of rectal MALT lymphoma in patients negative for H.pylori"Endoscopy. 34. 343-346 (2002)