title: Prevention of colitis by controlled oral drug delivery of carbon monoxide.
abstract: Carbon monoxide (CO) is an endogenous signal transmitter involved in numerous physiological processes including the gastrointestinal (GI) homeostasis. CO has been recognized as potential new therapeutic agent for motility related and inflammatory disorders of the GI tract. A therapeutic use, however, is challenged by inappropriate drug delivery modes. Here we describe a micro scale Oral Carbon Monoxide Release System (M-OCORS) designed for localized and controlled exposure of the GI tract with in situ generated CO. M-OCORS allowed for controlled release profiles lasting for several minutes or up to almost one day. These in vitro release profiles translated into a large pharmacokinetic design space following oral administration in mice and measured as CO-hemoglobin (CO-Hb) formation. M-OCORS with a release profile featuring exposure of the intestine was profiled in two independently performed studies demonstrating preventive effects in chemically induced colitis. M-OCORS significantly reduced damage scores and prevented upregulation of colitis biomarkers.
authors: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, Germany.
authors: Christoph
authors: C
authors: Steiger
authors: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors: Kazuhiko
authors: K
authors: Uchiyama
authors: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors: Tomohisa
authors: T
authors: Takagi
authors: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors: Katsura
authors: K
authors: Mizushima
authors: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors: Yasuki
authors: Y
authors: Higashimura
authors: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, Germany.
authors: Marcus
authors: M
authors: Gutmann
authors: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, Germany.
authors: Cornelius
authors: C
authors: Hermann
authors: Department of Chemistry, University of Cologne, Greinstrasse 4, 50939 Koeln, Germany.
authors: Svetlana
authors: S
authors: Botov
authors: Department of Chemistry, University of Cologne, Greinstrasse 4, 50939 Koeln, Germany.
authors: Hans-Günther
authors: HG
authors: Schmalz
authors: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors: Yuji
authors: Y
authors: Naito
authors: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, Germany. Electronic address: lorenz.meinel@uni-wuerzburg.de.
authors: Lorenz
authors: L
authors: Meinel
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002248:Carbon Monoxide / Q000008:administration & dosage* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003092:Colitis / Q000378:metabolism / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide
keywords: Carbon monoxide releasing molecule; Tablet; Therapeutic gas; Ulcerative colitis