Shikonin delivery nano system based on calcium alginate for targeted therapy of inflammatory bowel disease by modulating macrophage polarization

ABSTRACT Effective delivery of therapeutic drugs to colonic epithelial cells and macrophages is crucial for mitigating inflammation and repairing the intestinal barrier in inflammatory bowel disease (IBD). We developed a pH-triggered colonic targeted delivery nano system utilizing natural polymers, including chitosan (CS), hyaluronic acid (HA), and calcium alginate (ALG), encapsulating the active component shikonin (SK) to structure SK-loaded ALG/HA/CS delivery nano system (SK@LAS). The oral administration of SK@LAS specifically delivered SK in the colon via pH sensitivity and colonic targeting. SK@LAS was internalized by CD44 receptor-mediated endocytosis into macrophages. Furthermore, significant therapeutic effects of SK@LAS were observed in acute and chronic mouse colitis models, including reduced pro-inflammatory cytokines and mediators, increased expression of anti-inflammatory cytokines, and suppression of M1 polarization. Furthermore, SK@LAS upregulated the expression of tight junction proteins, thereby restoring intestinal barrier function. This colonic targeted delivery nano system exhibits promise as an oral drug delivery approach for the treatment of IBD.