Bioresponsive hydroxyethyl starch-flurbiprofen nanoparticles targeted to inflammatory microenvironments for post-operative pain management

Post-operative pain can hinder post-operative recovery by activating the neuroendocrine stress response to surgery, caused by inflammation. Preemptive analgesia using flurbiprofen preoperatively is a potential treatment option to avoid hyperalgesia and prevent post-operative pain. However, the hydrophobicity and short in vivo elimination half-life of flurbiprofen are limitations. In this study, a strategy is presented for targeting inflammatory microenvironments using bioresponsive nanoparticles that simultaneously alleviate inflammation and inhibit hyperalgesia, effectively managing post-operative pain in rats. Our study demonstrates that flurbiprofen-conjugated hydroxyethyl starch can self-assemble into nanoparticles in water, imparting flurbiprofen with higher solubility in water and a longer half-life. Additionally, these biocompatible flurbiprofen-conjugated hydroxyethyl starch nanoparticles accumulate in the incision. Pathological analysis of nerves indicates that hyperalgesia was effectively inhibited by the preoperative administration of HES-Flurbiprofen nanoparticles in the rat incisional pain model. This hydroxyethyl starch-based nanoparticle system also suggests a promising and straightforward strategy for developing biocompatible and bioresponsive formulations for post-operative pain management.