Microfluidic-based oral mucoadhesive nanozyme microspheres for immune modulation of xerostomia

Xerostomia is defined as the clinical syndrome characterized by reduced salivary secretion and/or abnormal composition of saliva, with the essential pathological basis being salivary gland dysfunction. These symptoms could not be effectively and persistently alleviated using current therapies. This study presents a microfluidics-based oral adhesive nanozyme microsphere system for the treatment of xerostomia. The adhesive hydrogel coating on the outer layer of the microspheres can rapidly establish robust adhesion to the moist oral mucosa. Furthermore, it contains cerium oxide nanoparticles (CeNP) which would be slowly released in presence of saliva collagenase enzyme. Of particular interest are the remarkable anti-inflammatory and antioxidant properties of CeNP, which have demonstrated significant efficacy in neutralizing reactive oxygen species (ROS) produced by macrophages and markedly suppressing proinflammatory responses. Animal experiments have revealed this microsphere system can effectively alleviate the infiltration of inflammatory cells into the salivary glands and maintain the integrity of the salivary gland duct and acinus. Based on the transcriptomic analysis, adCe-MS demonstrates a robust therapeutic effect on mice with xerostomia by significantly downregulating key inflammatory pathways and chemokines while upregulating salivary secretion-related genes. These results suggest that this drug delivery system not only presents a novel strategy for mucosal nanomedicine administration but also offers an effective solution for the treatment of xerostomia. • Integrated Functional Design: Combining microfluidic electrospray fabrication with nanoceria-alginate core and adhesive hydrogel coating to achieve simultaneous mucosal retention and controlled drug release. • Pathology-Responsive Release: Enzymatically triggered CeNP delivery specifically under pathological collagenase-rich conditions. • Dual Antioxidant-Anti-inflammatory Action: Cerium oxide nanoparticles provide simultaneous SOD/CAT-mimetic activities and anti-inflammatory effects. • Mechanistic Validation: Transcriptomic profiling confirms dual modulation of inflammatory pathways and salivary secretion genes.