Design, optimization, and characterization of a thermo-responsive hydrogel as submucosal injection agent for...

Submucosal injection is essential during endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) to create a protective cushion and enable safe lesion removal. However, commonly used solutions such as normal saline diffuse rapidly and provide only transient mucosal elevation. This study aimed to develop and characterize a thermosensitive hydrogel based on poloxamer 407 (P407) to achieve a more sustained submucosal lift. A design of experiments approach identified an optimized formulation containing 20% (w/v) P407 in water for injection, exhibiting suitable gelation temperature, gelation time, osmolality, and pH. Rheological analyses demonstrated low viscosity at room temperature, rapid sol-gel transition near 30°C, and the formation of a stable elastic network at 37°C. In vitro degradation showed progressive erosion, with complete dissolution within 24 h. Sterile filtration and needle passage produced only minor changes in viscoelastic moduli and did not alter gelation kinetics. Ex vivo studies using porcine gastrointestinal tissues confirmed that the hydrogel generated an initial mucosal lift comparable to 0.9% NaCl but maintained the elevation significantly longer. These findings demonstrate that P407-based thermosensitive hydrogel displayed favorable physicochemical, rheological, and functional properties for submucosal injection, supporting its potential as a next-generation lifting agent for EMR and ESD. Further in vivo studies are warranted to assess performance, safety, and clinical applicability.