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ACS Biomater Sci Eng. 2017;3(8):1853-1860. doi: 10.1021/acsbiomaterials.7b00262. Epub 2017 Jun 5.

Succinylated chitosan derivative has local protective effects on intestinal inflammation.

Author information

1
Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
2
Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, 625 Harrison Street, West Lafayette, IN 47907, USA.
3
Department of Pediatrics and the Congenital Heart Center, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
4
Weldon School of Biomedical Engineering, Purdue University, 206 South Martin Jischke Drive, West Lafayette, IN 47907, USA.

Abstract

We have previously reported on the anti-inflammatory effects of a water-soluble chitosan derivative, zwitterionic chitosan (ZWC). In the present study, we hypothesized that orally-administered ZWC would provide local anti-inflammatory effects in the intestinal lumen. ZWC indeed showed anti-inflammatory effects in various in-vitro models including peritoneal macrophages, engineered THP1 monocytes, and Caco-2 cells. In Caco-2 cells, ZWC applied before the lipopolysaccharide (LPS) challenge was more effective than when it was applied after it in preventing LPS-induced cell damage. When administered to mice via drinking water as a prophylactic measure, ZWC protected the animals from 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis, helping them to recover the body weight, restore the gross and histological appearance of the colon, and generate FoxP3+ T cells. In contrast, orally-administered ZWC did not protect the animals from LPS-induced systemic inflammation. These results indicate that orally-administered ZWC reaches the colon with minimal absorption through the upper gastrointestinal tract and provides a local anti-inflammatory effect.

KEYWORDS:

Colitis; anti-inflammatory; oral administration; preventive therapy; water-soluble chitosan

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