Flurbiprofen-loaded thermosensitive spray hydrogel for contactless analgesia and anti-inflammation in acute muscle contusion

Exercise-induced skeletal muscle contusion is common in sports, yet treatment is challenging: cold compression can slow recovery, oral NSAIDs may cause systemic side effects, and conventional topicals often have poor skin penetration and limited retention. Here, we developed a flurbiprofen-loaded thermosensitive sprayable hydrogel (FluSG) composed of HPMC and Pluronic F127 to enable contactless application, rapid gel formation at skin temperature (∼37 °C), sustained local drug release, and localized anti-inflammatory analgesia with minimal systemic toxicity. FluSG demonstrated reversible sol–gel transition near 37 °C, shear-thinning sprayability, and ∼48 h sustained flurbiprofen release in vitro, along with good cytocompatibility and hemocompatibility. In a murine closed gastrocnemius contusion model, a single FluSG spray significantly reduced mechanical and thermal hyperalgesia, edema, and muscle fiber damage compared with blank hydrogel or saline. Mechanistically, FluSG downregulated CGRP and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17) while increasing anti-inflammatory mediators (IL-10, TGF-β1), promoting a repair-favorable inflammatory environment. Systemic biosafety tests showed no hepatic, renal, or visceral toxicity. Overall, FluSG provides a convenient, self-applicable spray platform with promising potential for first-aid and rehabilitation after acute sports-related soft tissue injuries.