Commensal flora triggered target anti-inflammation of alginate-curcumin micelle for ulcerative colitis treatment

Ulcerative colitis (UC) is a chronic, idiopathic inflammatory bowel disease characterized by dysregulation of colon immune response. Curcumin (Cur) has strong anti-inflammatory activities, but the application is severely hindered by the extremely hydrophobicity and pitiful bioavailability. Alginate (Alg), a natural polysaccharide with ideal solubility and biosafety, was introduced to prepare the esterified alginate-curcumin conjugate (AlgCur) and constructed stable Alg-Cur micelle in physiological solutions. Compared with crystalline Cur, the target anti-inflammatory activities of Alg-Cur were systematically investigated. The results showed that Alg-Cur exerted effective anti-inflammatory effects in Raw 264.7 cells. After oral administration, 92.32 % of Alg-Cur reached colon, and the ester bonds were quickly sheared by abundant esterase produced by commensal anaerobic flora. The released Cur was quickly absorbed in-situ in monomolecular state, and effectively ameliorated the colonic inflammation and tissue damage by inhibiting the TLR4 expression in colonic epithelial cell, reducing the transcription and expression of the pro-inflammation cytokines downstream, as well as the infiltration of lymphocytes, macrophages and neutrophils. The Alg-Cur micelle effectively enhanced the hydrophilicity and bioavailability of Cur, and the commensal flora triggered Cur release showed great potential for UC treatment.