Lu_2025_Regen.Biomater_12_rbaf012

Acute pancreatitis (AP) is a potentially highly fatal inflammatory disease characterized by the generation of high level of reactive oxygen species (ROS) of mass recruited inflammatory macrophages in pancreatic tissue. Many natural product antioxidants have been explored to treat AP due to their superiority in biosafety while the therapeutic application is restricted by their low ROS elimination as well as the rapid metabolism caused by small molecular weight and fast absorption. Herein, a new natural product-based nano-antioxidant (FA@zein-CS) that can overcome these problems was developed for the treatment of AP by encapsulating ferulic acid (FA) into the zein based nanoparticles and then hybridizing of chondroitin sulfate (CS). The FA@zein-CS would not only efficiently target to the inflamed pancreatic tissue by the specific binding of CS to CD44, but also effectively initiate the release of FA and zein degradation product in response to intracellular pH/GSH/ROS to achieve synergistic antioxidant effect. In addition, thanks to the fact that all components were derived from natural products, the FA@zein-CS held the excellent biocompatibility. In vivo results disclosed that the FA@zein-CS significantly reduced pancreatic structural damage and restored the pancreatic function with serum amylase and lipase reduced by 61.8% and 82.8%, respectively. This natural product-based nano-antioxidant holds great clinic potential for AP.