Formulation of a thermo-sensitive hydro-gel for ulcerative colitis treatment

Abstract

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that causes chronic intestinal inflammation in gastrointestinal (GI) tract, mainly in innermost lining of colonic mucosa. In any of the UC drug therapy regimens, maintaining remission is challenging and about 20-40% of patients don't respond to conventional UC medications, namely, amino salicylates, steroids and immunosuppressive drugs. These agents can weaken the patient's immune system thus enhancing the risk of infectious diseases. Therefore, in our exploration we probed to test marine-derived anti-inflammatory compounds as potential agents to treat UC. Fucoidan, a complex fucose-rich sulphated polysaccharide originated in edible brown algae with known anti-inflammatory properties was isolated from Turbinaria ornate. Collagen (Achillis tendon) is another agent that may provide a beneficial effect in wound healing and tissue regeneration. Collagen was also reported to possess anti-UC properties. Collagen has a limitation of being in solution form even at high concentrations. We therefore formulated fucoidan with collagen that underwent a sol-gel transition and yielded a gel like consistency in situ. This formulation showed sustained release of fucoidan for about 12 hours. The fucoidan, collagen and the fucoidan-collagen formulation were tested in the dextran sodium sulfate (DSS) induced colitis model in mice. In comparison to the vehicle treated group, fucoidan-collagen hydrogel formulation led to significant reduction in the clinical scores and rectal bleeding, which was higher than the reference standard, mesalamine and those seen with fucoidan and collagen given alone.

Keywords: Collagen; Docking; Fucoidan; Mesalamine; Ulcerative colitis; in situ hydrogel.