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Orally delivered polycurcumin responsive to bacterial reduction for targeted therapy of inflammatory bowel disease
Inflammatory bowel disease (IBD) such as Crohn’s disease and ulcerative colitis is a chronic autoimmune disease affecting nearly five million people worldwide. Among all drug delivery system, oral administration is the most preferable route for colon-specific targeting and the treatment of IBD. Here...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240970/ https://www.ncbi.nlm.nih.gov/pubmed/28156160 http://dx.doi.org/10.1080/10717544.2016.1245367 |
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author | Qiao, Hongzhi Fang, Dong Chen, Jing Sun, Yuan Kang, Chen Di, Liuqing Li, Junsong Chen, Zhipeng Chen, Jun Gao, Yahan |
author_facet | Qiao, Hongzhi Fang, Dong Chen, Jing Sun, Yuan Kang, Chen Di, Liuqing Li, Junsong Chen, Zhipeng Chen, Jun Gao, Yahan |
author_sort | Qiao, Hongzhi |
collection | PubMed |
description | Inflammatory bowel disease (IBD) such as Crohn’s disease and ulcerative colitis is a chronic autoimmune disease affecting nearly five million people worldwide. Among all drug delivery system, oral administration is the most preferable route for colon-specific targeting and the treatment of IBD. Herein, an amphiphilic curcumin polymer (PCur) composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic curcumin (Cur) linked by disulfide bond was synthesized and characterized. The sufficient solubility, nano-scaled size and close to the neutral surface potential of PCur lead to preferential accumulation of the active drug in the inflamed regions of the gut. Moreover, PCur showed limited drug release and enhanced robustness under the physiological pH of the gastrointestinal tract (GIT), and a significantly elevated release was observed when responding to a bacterial reduction in the colon. Furthermore, cellular studies confirmed PCur had low cytotoxicity and increased transmembrane permeability, resulting in improved oral bioavailability evidenced by in vivo pharmacokinetics of rats. Finally, with DSS-induced murine model of IBD, we demonstrated that orally administered PCur ameliorated the inflammatory progression in the colon and could protect mice from IBD. In conclusion, it is illustrated that the developed PCur conjugate could potentially be employed as a colon-specific candidate for IBD treatment. |
format | Online Article Text |
id | pubmed-8240970 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-82409702021-07-08 Orally delivered polycurcumin responsive to bacterial reduction for targeted therapy of inflammatory bowel disease Qiao, Hongzhi Fang, Dong Chen, Jing Sun, Yuan Kang, Chen Di, Liuqing Li, Junsong Chen, Zhipeng Chen, Jun Gao, Yahan Drug Deliv Research Article Inflammatory bowel disease (IBD) such as Crohn’s disease and ulcerative colitis is a chronic autoimmune disease affecting nearly five million people worldwide. Among all drug delivery system, oral administration is the most preferable route for colon-specific targeting and the treatment of IBD. Herein, an amphiphilic curcumin polymer (PCur) composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic curcumin (Cur) linked by disulfide bond was synthesized and characterized. The sufficient solubility, nano-scaled size and close to the neutral surface potential of PCur lead to preferential accumulation of the active drug in the inflamed regions of the gut. Moreover, PCur showed limited drug release and enhanced robustness under the physiological pH of the gastrointestinal tract (GIT), and a significantly elevated release was observed when responding to a bacterial reduction in the colon. Furthermore, cellular studies confirmed PCur had low cytotoxicity and increased transmembrane permeability, resulting in improved oral bioavailability evidenced by in vivo pharmacokinetics of rats. Finally, with DSS-induced murine model of IBD, we demonstrated that orally administered PCur ameliorated the inflammatory progression in the colon and could protect mice from IBD. In conclusion, it is illustrated that the developed PCur conjugate could potentially be employed as a colon-specific candidate for IBD treatment. Taylor & Francis 2017-02-03 /pmc/articles/PMC8240970/ /pubmed/28156160 http://dx.doi.org/10.1080/10717544.2016.1245367 Text en © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/Licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Qiao, Hongzhi Fang, Dong Chen, Jing Sun, Yuan Kang, Chen Di, Liuqing Li, Junsong Chen, Zhipeng Chen, Jun Gao, Yahan Orally delivered polycurcumin responsive to bacterial reduction for targeted therapy of inflammatory bowel disease |
title | Orally delivered polycurcumin responsive to bacterial reduction for targeted therapy of inflammatory bowel disease |
title_full | Orally delivered polycurcumin responsive to bacterial reduction for targeted therapy of inflammatory bowel disease |
title_fullStr | Orally delivered polycurcumin responsive to bacterial reduction for targeted therapy of inflammatory bowel disease |
title_full_unstemmed | Orally delivered polycurcumin responsive to bacterial reduction for targeted therapy of inflammatory bowel disease |
title_short | Orally delivered polycurcumin responsive to bacterial reduction for targeted therapy of inflammatory bowel disease |
title_sort | orally delivered polycurcumin responsive to bacterial reduction for targeted therapy of inflammatory bowel disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240970/ https://www.ncbi.nlm.nih.gov/pubmed/28156160 http://dx.doi.org/10.1080/10717544.2016.1245367 |
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