Oral chitosan-cyclodextrin “shell-core” nanoparticles co-loaded Rhein and chlorogenic acid for ulcerative colitis treatment

Abstract

The food-derived ingredients Rhein (RH) and chlorogenic acid (CGA) have DEMONSTRATED a potential synergistic effect in the treatment of ulcerative colitis (UC) through their anti-inflammatory and antioxidant properties. However, the oral co-delivery of RH and CGA faces challenges such as differences in hydrophilicity and hydrophobicity, gastrointestinal instability, and inadequate colonic targeting. To address these issues, shell-core nanoparticles were developed for the co-encapsulation of RH and CGA (CP@CGA-FA/TA@RH NPs). These nanoparticles utilize cyclodextrin-based polymers and folate-amantadine polymers to form a supramolecular core that targets macrophages for anti-inflammatory action with RH, while chitosan cross-link to CGA in the outer shell provides microenvironment-sensitive antioxidant release. The results indicate that CP@CGA-FA/TA@RH NPs could effectively inhibit the classical TLR4/MyD88/NF-κB-mediated anti-inflammatory pathway and activate the Nrf2/HO-1-mediated antioxidant pathway, offering a novel approach to UC treatment. Q-value analysis confirms the substantial co-medication effect between RH and CGA. This study is the first to develop a nano-system combining two food-derived ingredients for the integrated treatment of UC.