Engineered baicalein-decorated zinc phosphates for synergistic alleviation of inflammatory bowel disease by repairing mucosal barrier and relieving oxidative stress

Orally administrating baicalein-decorated zinc phosphates (ZnBM) were engineered for mucosal barrier improvement and intestinal inflammation relief. ZnBM with a size of 1.78 µm comprised 5.58 wt% of baicalein and 13.17 wt% of Zn. The incorporation of baicalein endowed ZnBM with excellent radical scavenging activities. ZnBM exhibited good stability with negligible zinc re-lease in PBS solution for 2 days, and 32.82% of zinc could reach the gut. In addition, ZnBM polar-ized macrophages into anti-inflammatory M2 type and effectively scavenged intracellular ROS of LPS-treated RAW264.7. Meanwhile, ZnBM effectively scavenged intracellular ROS of PMA-induced Caco-2 cells and exerted a reparative effect on LPS-damaged Caco-2 monolayer, causing obvious improvement of barrier function. Reduced systemic exposure to FITC-dextran was observed to illustrate barrier restoration by ZnBM, which was achieved through upregula-tion of tight junction proteins expression. Notably, the commonly used clinical drug, 5-aminosalicylic acid was toxic to liver and kidney, and commercial ZnO caused death of mice during treatment. Apparently, the therapeutic effect of ZnBM was significantly better than that of baicalein alone in chronic colitis. Overall, ZnBM exhibited outstanding therapeutic efficacy and was expected to be used in the clinical treatment of colitis due to its effectiveness, biosecuri-ty, facile preparation, and easy storage.