Mesalamine colon-retentive microparticles for treatment of ulcerative colitis

Ulcerative colitis (UC) is a lifelong inflammatory disease affecting the rectum and colon. Mesalazine (MSZ) is the first-line clinical treatment for UC but has a short half-life of 0.5 to 2 h, necessitating multiple daily doses. Moreover, most of the drug is absorbed in the stomach and small intestine, resulting in low drug concentrations at the lesion site and limited therapeutic efficacy. Herein, we developed a coating material mannosylated ethyl cellulose (Man-EC) to confer colon-retentive properties to MSZ microparticles by leveraging the adhesive property of mannose to macrophages at the UC site. MSZ microparticles with high mechanical strength, good roundness, and a particle size below 200 μm were prepared using a water-in-oil-in-water (W/O/W) double emulsion method. A sustained-release layer of Man-EC and an enteric coating of Eudragit S100 were sequentially applied to the particle surface, yielding fine-sized enteric sustained-release microparticles with colon-retentive properties. Upon dissolution of the enteric coating in the colon, mannose on the microparticle surface is exposed and binds to mannose-related receptors on macrophages at the UC site. This adhesion enables the microparticles to remain at the colonic lesion site and slowly release the encapsulated MSZ, achieving sustained drug delivery for enhanced local therapy.