Prevention of colitis by controlled oral drug delivery of carbon monoxide
| Autor: | Yuji Naito, Hans-Günther Schmalz, Christoph Steiger, Lorenz Meinel, Katsura Mizushima, Tomohisa Takagi, Cornelius Hermann, Marcus Gutmann, Svetlana Botov, Yasuki Higashimura, Kazuhiko Uchiyama |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Cell Survival Pharmaceutical Science Administration Oral Endogeny Pharmacology 010402 general chemistry 01 natural sciences 03 medical and health sciences Mice Drug Delivery Systems Downregulation and upregulation Pharmacokinetics Oral administration medicine Organometallic Compounds Animals Colitis Carbon Monoxide Dose-Response Relationship Drug Chemistry medicine.disease Controlled release 0104 chemical sciences Mice Inbred C57BL 030104 developmental biology Drug delivery NIH 3T3 Cells Homeostasis |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 239 |
| ISSN: | 1873-4995 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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