P142 TARGETED COLON DELIVERY OF NIPEP-IM-0127 PEPTIDE FOR INFLAMMATORY BOWEL DISEASE (IBD) TREATMENT

Abstract

Abstract Under Inflammatory bowel disease (IBD), autoantibody-type VII collagen complex can induce autoimmune reaction and continue with the inflammation. Here, we introduced synthetic 19 amino acid sequenced peptide termed as NIPEP-IM-0127 that inhibits autoantibody-type VII collagen complex formation. The NIPEP-IM-0127 was further formulated for oral administration. Primary function of NIPEP-IM-0127 selectively localizes to wound gut barrier and masks exposed type VII collagen, which is the starting of autoimmune reaction. Disrupted type VII collagen by the disease was bound to the applied peptide, which interfere autoimmune complex formation by competitive binding inhibition between antibody and peptide. NIPEP-IM-0127 thus recovered inflammatory cytokine level by the inhibition of immune complex creation. The orally applied NIPEP-IM-0127 peptide was primarily detected at the surface of colon tissue after 9 hours of administration, while no distributions were shown in other organs. Most importantly, significant mucosal regeneration and healing has been achieved by NIPEP-IM-0127. The following GLP toxicity studies, including safety pharmacology, genotoxicity, single and repeated dose toxicity, demonstrated that NIPEP-IM-0127 showed no significant toxic effect in in mouse and monkey. Taken together, the NIPEP-IM-0127 is suggested to be a novel therapeutic candidate for IBD treatment by the dual effects combining immune modulation and intestine barrier healing.