Research on triamcinolone-loaded thermosensitive chitosan hydrogels for preventing esophageal stricture induced by endoscopic submucosal dissection

Abstract

Early-stage esophageal cancer is primarily treated by endoscopic submucosal dissection (ESD). However, extensive mucosal dissection creates a significant risk of postoperative esophageal stricture. Clinically, postoperative stricture can be prevented by glucocorticoids; however, there are drawbacks to both systemic and local administration of glucocorticoids, and improving drug administration methods is crucial. In this study, we developed a chitosan-based thermosensitive hydrogel for triamcinolone (TA) delivery. Our results indicated that the hydrogel remains liquid at low temperatures and can be injected into the esophageal wound site through an endoscopic biopsy channel. Upon reaching body temperature, the hydrogel undergoes spontaneous gelation and firmly adheres to the wound surface. The liquid phase enables convenient and precise delivery, while the gel phase achieves remarkable adhesion, tensile strength, and resistance to degradation. Moreover, the hydrogel exhibited an extended release duration of >10 days when loaded with a 10 mg dose. In vitro studies revealed that the hydrogel suppresses the proliferation and fibrogenesis of human scar fibroblasts (HKF). In a rat skin dermal defect model, the hydrogel attenuated keloid formation during the healing process. Consequently, the chitosan-based thermosensitive hydrogel developed in this study for triamcinolone delivery may be an effective tool for preventing post-ESD esophageal stricture.