Universität zu Köln

Steiger, Christoph, Uchiyama, Kazuhiko, Takagi, Tomohisa, Mizushima, Katsura, Higashimura, Yasuki, Gutmann, Marcus, Hermann, Cornelius, Botov, Svetlana, Schmalz, Hans-Guenther ORCID: 0000-0003-0489-1827, Naito, Yuji and Meinel, Lorenz ORCID: 0000-0002-7549-7627 (2016). Prevention of colitis by controlled oral drug delivery of carbon monoxide. J. Control. Release, 239. S. 128 - 137. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1873-4995

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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. (C) 2016 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Steiger, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Uchiyama, Kazuhiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Takagi, Tomohisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Mizushima, Katsura UNSPECIFIED UNSPECIFIED UNSPECIFIED Higashimura, Yasuki UNSPECIFIED UNSPECIFIED UNSPECIFIED Gutmann, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Hermann, Cornelius UNSPECIFIED UNSPECIFIED UNSPECIFIED Botov, Svetlana UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmalz, Hans-Guenther UNSPECIFIED orcid.org/0000-0003-0489-1827 UNSPECIFIED Naito, Yuji UNSPECIFIED UNSPECIFIED UNSPECIFIED Meinel, Lorenz UNSPECIFIED orcid.org/0000-0002-7549-7627 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-258500
DOI:	10.1016/j.jconrel.2016.08.030
Journal or Publication Title:	J. Control. Release
Volume:	239
Page Range:	S. 128 - 137
Date:	2016
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1873-4995
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Organic Chemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACID-INDUCED COLITIS; TRICARBONYL COMPLEXES; HEME OXYGENASE-1; CELL VIABILITY; CO; MOLECULES; RELEASE; MICE; INHALATION; EXPOSURE Multiple languages Chemistry, Multidisciplinary; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25850