Mucin armoured diethylaminoethyl-dextran cloaked rebamipide based oral nanoformulation for the therapy of inflammatory bowel disease

One of the major challenges in the treatment of inflammatory bowel disease (IBD) is the development of an oral drug delivery system that can provide extended GI residence time. In this work, a nanoformulation formed by Rebamipide (Re) encapsulated into mucin DEAE-dextran armored nanoparticles (M@D@Re-SCNPs) is introduced, which utilizes the core of caprylic acid (C)/6-O-stearoyl ascorbic acid (S). These M@D@Re-SCNPs were fabricated to provide both gastro-resistant and mucoadhesion properties of the nanoparticles. The M@D@Re-SCNPs showed pH-independent structural integrity in the gastric environment and proved to have a good mucosal binding capacity in the colon for long intestinal retention of up to 48 h. In terms of therapeutic efficacy, post-oral administration of M@D@Re-SCNPs strongly reduce the colon inflammatory status and the expression of inflammatory biomarkers like nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and phosphoinositide 3-kinase (PI3K) when compared with free rebamipide. The trapped rebamipide inhibits the production of pro-inflammatory mediators and promotes the production of mucin 2 (Muc2) protein, which promotes colon mucosal regeneration and goblet cell viability. Based on the necessity of controlling drug release and regulation of drug action for complete IBD treatment, we believe that the M@D@Re-SCNPs are a promising drug delivery system for UC treatment.