Optimized Formulation of Sulfasalazine and Probiotic-Loaded Carrageenan Microparticles Using Design of Experiments for Effective Colitis Management.

Abstract

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by mucosal inflammation and epithelial barrier dysfunction. Sulfasalazine, a standard antiinflammatory drug, and probiotics, known for gut microbiota modulation, have both shown efficacy in UC management. However, their combined delivery to the colon remains underexplored. This study aimed to develop a colon-targeted microparticulate formulation containing sulfasalazine and a probiotic strain to enhance anti-inflammatory action and therapeutic effectiveness against UC.

Methods: Microparticles were prepared using a Design of Experiments (DoE) approach, optimizing carrageenan and calcium chloride dihydrate concentrations and stirring speed. The probiotic was co-encapsulated to maintain viability during processing. In vitro evaluations included drug release studies and Caco-2 cell line assays for epithelial integrity, ROS generation, and NF-κB expression. In vivo efficacy was assessed using an acetic acid-induced colitis model, with evaluations based on inflammation severity, tissue damage and histopathology.

Results: Optimized microparticles ensured sustained sulfasalazine release and preserved probiotic viability. In vitro, the formulation improved epithelial barrier function, reduced ROS and proinflammatory cytokines, and suppressed NF-κB expression. In vivo, treated animals showed significant reduction in colitis severity, improved tissue integrity and better histopathological outcomes compared to controls.

Discussion: The combined sulfasalazine-probiotic microparticles effectively addressed both symptomatic relief and the inflammatory cascade in UC. Probiotics enhanced gut barrier protection, while sustained sulfasalazine release ensured localized therapeutic action. The synergy between drug and probiotic delivery offers a novel approach over conventional therapies.

Conclusion: This study presents a promising colon-targeted microparticulate system combining sulfasalazine and probiotics for effective UC management. The dual-action formulation offers enhanced anti-inflammatory efficacy, reduced tissue damage, and better disease control, supporting its potential in future clinical applications.