A ROS-responsive nanoplatform for synergistic pain relief and gastrointestinal recovery in intestinal ischemia-reperfusion injury

IntroductionThere is a clinical contradiction between postoperative analgesia and gastrointestinal functional recovery following intestinal ischemia-reperfusion (I/R) injury.MethodsIn this study, a reactive oxygen species (ROS)-responsive nanoplatform (LA-CLX-NP) was constructed by conjugating DSPE-PEG with α-lipoic acid (LA) followed by self-assembly and encapsulation of celecoxib.ResultsThe nanoparticles exhibited uniform size, good stability, and ROS/pH dual-responsive drug release properties. In vitro, LA-CLX-NP was efficiently internalized by macrophages and, compared with free drugs, more effectively scavenged ROS, restored redox balance, and modulated inflammatory cytokines. In a mouse model of intestinal I/R injury, LA-CLX-NP significantly reduced diarrhea incidence, increased mechanical withdrawal threshold, decreased abdominal licking and scratching behaviors, preserved ZO-1 tight junctions, suppressed COX-2 overexpression, and normalized serum cytokine profiles, with superior efficacy to single agents.DiscussionThis strategy achieves on-demand delivery of celecoxib to the inflamed intestine, exerts synergistic anti-inflammatory and antioxidant effects, and thereby reconciles effective pain relief with rapid gastrointestinal recovery, offering a new approach for postoperative management of intestinal I/R injury.