Oral cyclodextrin supramolecular for ulcerative colitis treatment through macrophages targeting / ROS response-based accurate on-demand drug release strategy

Cyclodextrins (CDs) have been applied widely as an oral micro-nano drug delivery material for the treatment of ulcerative colitis (UC) because of their stability around the stomach. However, the further application of CDs is hindered due to their inherent poor targeting and controlled release properties. In this study, CD-supramolecular nanoparticles ( [email protected] ) were developed based on the structural characteristics of CDs (e.g., multi-group modifiability and hydrophobic cavity) to encapsulate rhein (RH) for oral delivery against UC. The [email protected] showed an average size of 154.70 ± 1.80 nm and exhibited high encapsulation efficiency (95.55 ± 2.37 %). When incubated in simulated gastric fluid for 2 h, [email protected] only released 20.3 ± 0.47 % RH due to the protection of supramolecular effects of CDs. However, RH was rapidly released from [email protected] (released 66.3 ± 2.50 %) after H 2 O 2 was treated with the assistance of the ROS-sensitive properties. Moreover, [email protected] were taken up by macrophages in 1.5 times higher amounts than preparations which did not have CD44-targeted effects. Notably, the results showed that [email protected] with an accurate on-demand drug release strategy achieved the best anti-inflammatory and antioxidant effects, and they are expected to be a promising carrier in the UC treatment.