Succinylated Chitosan Derivative Has Local Protective Effects on Intestinal Inflammation

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-trinitrobenzenesulfonic 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.