Dual‐Targeted Nanoparticle‐in‐Microparticle System for Ulcerative Colitis Therapy

Abstract Conventional oral therapy for ulcerative colitis (UC) is associated with premature release or degradation of drugs in the harsh gastrointestinal environment, resulting in reduced therapeutic effectiveness. Consequently, the present study aims to develop a dual‐targeted delivery system with a nanoparticle‐in‐microparticle (nano‐in‐micro) structure. The prepared Asiatic Acid‐loaded delivery system (AA/CDM‐BT‐ALG) has pH‐sensitive properties. Cellular uptake evaluation confirms that nanoparticles exhibit targeted absorption by macrophages and Caco‐2 cells through mannose (Man) receptor and biotin‐mediated endocytosis, respectively. Therefore, this mechanism effectively enhances intracellular drug concentration. Additionally, the biodistribution study conducted on the gastrointestinal tract of mice indicates that the colon of the microspheres group shows higher fluorescence intensity with longer duration than the other groups. This finding indicates that the microspheres exhibit selective accumulation in areas of colon inflammation. In vivo experiments in colitis mice showed that AA/CDM‐BT‐ALG significantly alleviates the histopathological characteristics of the colon, reduced neutrophil, and macrophage infiltration, and decreases pro‐inflammatory cytokine expression. Furthermore, the effect of AA/CDM‐BT‐ALG on colitis is validated to be closely related to the TLR4/MyD88/NF‐κB signaling pathway. The present findings suggest that the development of a dual‐targeted delivery system is accomplished effectively, with the potential to serve as a drug‐controlled release system for treating UC.