Dual-Targeted Nanoparticle-In-Microparticle System for Ulcerative Colitis Therapy.

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, we aimed 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) had pH-sensitive properties. Cellular uptake evaluation confirmed that nanoparticles exhibited 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 indicated that the colon of the microspheres group showed higher fluorescence intensity with longer duration than the other groups. This finding indicated that the microspheres exhibited selective accumulation in areas of colon inflammation. In vivo experiments in colitis mice showed that AA/CDM-BT-ALG significantly alleviated the histopathological characteristics of the colon, reduced neutrophil and macrophage infiltration, and decreased pro-inflammatory cytokine expression. Furthermore, the effect of AA/CDM-BT-ALG on colitis was 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 has been accomplished effectively, with the potential to serve as a drug-controlled release system for treating UC. This article is protected by copyright. All rights reserved.