Environment-Responsive Sustained-Release Nanoparticles for the Protection, Delivery and Release of Clove Essential...

Bacterial colitis remains a global health challenge. Clove essential oil (CEO), a natural plant extract, exerts potent activity against enteropathogenic Escherichia coli (E. coli). But its poor water solubility and insufficient stability limit its translation into a therapeutic agent for E. coli-induced colitis. Herein, we first synthesized β-cyclodextrin-grafted chitosan nanoparticles (CS-g-CD NPs) by electrostatic interactions based on a pH response and enzymatic degradation synergy. Subsequently, with the assistance of ultrasound waves, CEO was loaded into the nanoparticles through van der Waals forces, ultimately constructing a colon-targeted delivery system (CEO/CS-g-CD NPs). This system not only enhanced the water solubility and stability of CEO, but also improved its bioavailability (enhanced by 120.10%) through protecting it from gastric acid degradation and prolonging intestinal retention. In vitro and in vivo studies demonstrated that CEO/CS-g-CD NPs effectively inhibited E. coli proliferation and suppressed its virulence gene expression. Consequently, these nanoparticles alleviated the inflammatory response triggered by bacterial infection, regulated gut microbiota homeostasis, and further promoted the repair of the damaged colonic barrier. This study developed an intelligent on-demand release strategy for poorly water-soluble natural products, markedly boosting their ameliorative effect on bacterial colitis and facilitating the application of these products in pharmaceutical sectors.