Microfluidic-based magnetic microspheres for targeted delivery of curcumin nanoparticles in gastroesophageal reflux disease therapy

This magnetic drug delivery system is based on droplet microfluidic technology, with uniform size of the microspheres and controllable mode. • MNPs enabled esophageal retention under magnetic fields, while GelMA component enables controlled curcumin release under reflux conditions. • These multifunctional microspheres effectively address the challenges associated with targeted drug delivery to the esophagus. Activated molecular pathways with elevated chemokine secretion are critical in driving pathogenesis of the mucosal inflammation in gastroesophageal reflux disease (GERD). The therapeutic efficacy of acid-suppressants is often constrained in GERD patients due to the high prevalence of non-acid reflux. Curcumin, a natural polyphenol with robust anti-inflammatory and antioxidant effects, offers promising therapeutic potential. In this study, leveraging the favorable biocompatibility and bioactive property of gelatin methacryloyl (GelMA), we developed GelMA microspheres as microcarriers encapsulating curcumin nanoparticles (Cur) for local treatment of GERD. The further incorporation of magnetic nanoparticles (MNPs) facilitates esophageal localization of the microspheres under an external magnetic field. Additionally, Cur-MNPs@GelMA microspheres sustain drug release in simulated gastric fluid, ensuring effective local concentrations. In vitro and in vivo investigations corroborated that Cur-MNPs@GelMA microspheres markedly inhibited the generation of inflammatory cytokines and reactive oxygen species (ROS). Mechanistically, the microspheres can restore mitochondrial function and inhibit NF-κB pathway. Furthermore, the multifunctional microspheres can effectively ameliorate histopathological damage and suppress inflammation in a mouse model of GERD. These findings endorse the therapeutic potential of Cur-MNPs@GelMA microspheres as a novel clinical intervention for GERD. Download: Download high-res image (192KB) Download: Download full-size image