Abstract
Inflammatory bowel disease is a chronic inflammation of the gastrointestinal tract with poor understanding of its pathogenesis and no effective cure. The goal of this study was to evaluate the feasibility of orally administered non-degradable polymeric chloroquine (pCQ) to locally reduce colon inflammation. The pCQ was synthesized by radical copolymerization of N-(2-hydroxypropyl)methacrylamide with methacryloylated hydroxychloroquine (HCQ). The anti-inflammatory activity of orally administered pCQ versus HCQ was tested in a mouse model of colitis induced by Citrobacter rodentium (C. rodentium). Single-dose pharmacokinetic and biodistribution studies performed in the colitis model indicated negligible systemic absorption (p ≤ 0.001) and localization of pCQ in the gastrointestinal tract. A multi-dose therapeutic study demonstrated that the localized pCQ treatment resulted in significant reduction in the colon inflammation (p ≤ 0.05). Enhanced suppression of pro-inflammatory cytokines IL-6 (p ≤ 0.01) and IL1-β and opposing upregulation of IL-2 (p ≤ 0.05) recently reported to be involved in downstream anti-inflammatory events suggested that the anti-inflammatory effects of the pCQ are mediated by altering mucosal immune homeostasis. Overall, the reported findings demonstrate a potential of pCQ as a novel polymer therapeutic option in inflammatory bowel disease with the potential of local effects and minimized systemic toxicity.
Original language | English (US) |
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Pages (from-to) | 158-170 |
Number of pages | 13 |
Journal | Acta Biomaterialia |
Volume | 82 |
DOIs | |
State | Published - Dec 2018 |
Keywords
- Chloroquine
- Citrobacter rodentium
- Colitis
- Inflammatory bowel disease
- Oral administration
- Pharmacokinetics
- Polymeric drug
ASJC Scopus subject areas
- Biotechnology
- Biomaterials
- Biochemistry
- Biomedical Engineering
- Molecular Biology