Abstract
BACKGROUND: Irritable bowel syndrome (IBS) requires long-term, site-specific therapy. Mebeverine hydrochloride is effective but limited by rapid metabolism and frequent dosing. This study aimed to develop colon-targeted, controlled-release nanoparticles to improve therapeutic efficacy and compliance. METHODS: Nanoparticles were prepared via chitosan-xanthan gum polyelectrolyte complexation and optimized using a Box-Behnken design. Molecular docking predicted strong binding of mebeverine to the muscarinic acetylcholine receptor (-7.4 kcal/mol). Optimized nanoparticles were enteric-coated with Eudragit S100 for pH-dependent colonic release and evaluated through in vitro dissolution and in vivo efficacy in an acetic acid-induced IBS-D rat model. RESULTS: Optimized nanoparticles showed a mean size of ~ 380 nm, zeta potential + 25 mV, and entrapment efficiency of 95%. In vitro, the enteric-coated formulation resisted gastric pH and released > 95% drug under colonic conditions within 12 h. In vivo, treated rats demonstrated significantly reduced visceral hypersensitivity (AWR score, p < 0.05), normalized intestinal motility (p < 0.05), and improved behavioral outcomes compared to the IBS group. High-dose nanoparticles performed better than the marketed sustained-release capsule. CONCLUSION: The chitosan-xanthan gum nanoparticle system enabled sustained, colon-specific delivery of mebeverine hydrochloride with superior therapeutic efficacy in vivo, offering a promising strategy for long-term IBS management.