Microfluidics-enabled polydopamine-coated selenium nanoparticles in hyaluronic hydrogel microspheres for targeted antioxidant and immunomodulatory therapy of ulcerative colitis

Ulcerative colitis (UC) is manifested by excessive oxidative stress and immune dysregulation in the colonic microenvironment. To address these pathological features, we developed a microfluidics-engineered oral delivery system comprising methacrylated hyaluronic acid (HAMA) hydrogel microspheres encapsulating polydopamine-coated selenium nanoparticles (CS-Se@PDA). The uniform microspheres featured a microfluidics-enabled structure that enabled stable CS-Se@PDA nanoparticles anchoring via electrostatic and covalent interactions. The PDA coating enhanced the stability, mucosal adhesion, and scavenging of reactive oxygen species (ROS) of the nanoparticles. At the same time, the HAMA shell provided pH-responsive protection and CD44-mediated targeting to inflamed colonic tissues. <i>In vitro</i> studies demonstrated excellent biocompatibility, effective ROS neutralization, and macrophage polarization toward the anti-inflammatory M2 phenotype. In a dextran sulfate sodium-induced colitis mouse model, oral administration of these microspheres significantly alleviated clinical symptoms, including ∼25 % mitigation of weight loss, increased colon length from 4.78 ± 0.3 cm to 6.83 ± 0.25 cm, and reduced histological damage. Furthermore, the treatment restored tight junction protein expression to approximately 60 % of normal levels for ZO-1 and about 55 % for Occludin, indicating substantial epithelial barrier repair, and effectively suppressed pro-inflammatory cytokines such as TNF-α and IL-6. Overall, this microfluidics-enabled, colon-targeted delivery system with integrated antioxidative and immunomodulatory functions offers a promising strategy for the non-invasive treatment of UC and other inflammation-associated gastrointestinal disorders.