A cell-permeable cytoplasmic transduction peptide (CTP; YGRRARRRARR) fused to the NEMO binding domain peptide (NBD; TALDWSWLQTE) that acts as a potent inhibitor of TNFa-stimulated NF-kB activity (IC50~50uM in HCT116 cells). Acts by interfering with the formation of active IKK complex and thereby prevents lkBa phosphorylation and its subsequent proteasomal degradation. Also blocks LPS-mediated increase in inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) activities. Colon-targeted capsules containing CTP-NBD are shown to reduce 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rodent models (4.5mg/kg/,p.o.) in vivo and diminish activities of myeloperoxidase and several inflammatory mediators.