Cyclosporine A‑Encapsulated pH/ROS Dual-Responsive Nanoformulations for the Targeted Treatment of Colitis in Mice

Inflammatory bowel disease (IBD) is a frequently occurring disease that seriously influences the patient’s quality of life. To decrease adverse effects and improve efficacy of therapeutics, nanomedicines have been widely used to treat IBD. However, how to thoroughly release payloads under an inflammatory microenvironment and synergistic therapy of IBD need to be further investigated. To address this issue, cyclosporine A (CsA)-loaded, folic acid (FA)-modified, pH and reactive oxygen species (ROS) dual-responsive nanoparticles (FA-CsA NPs) were fabricated using pH/ROS-responsive material as carrier. The prepared FA-CsA NPs had spherical shape and uniform size distribution and could smartly release their payloads under acid and/or ROS microenvironment. In vitro experiments demonstrated that FA-CsA NPs can be effectively internalized by activated macrophages, and the internalized NPs could down-regulate the expression of proinflammatory cytokines compared to free drug or nontargeted NPs. In vivo experiments verified that FA-CsA NPs significantly accumulated at inflammatory colon tissues and the accumulated NPs obviously improved the symptoms of colitis in mice without obvious adverse effects. In conclusion, our results provided a candidate for the targeted treatment of IBD