Injectable Thermosensitive Chitosan Solution with beta-Glycerophosphate as an Optimal Submucosal Fluid Cushion for Endoscopic Submucosal Dissection

Abstract

Endoscopic submucosal dissection (ESD) is a surgical procedure to remove early neoplastic lesions in the gastrointestinal tract with the critical issue of perforation. A submucosal fluid cushion, such as normal saline, is used as a cushioning agent to prevent perforation; however, its cushioning maintenance is insufficient for surgery. In this study, we introduce an injectable thermosensitive chitosan solution (CS) with beta-glycerophosphate (beta-GP) as a submucosal injection agent for ESD. The CS/beta-GP system with optimal beta-GP concentration showed drastic viscosity change near body temperature while other commercial products did not. Additionally, the injectability of the solution was similar to or greater than other commercial products. The solution with low beta-GP concentration showed low cytotoxicity similar to other products. An in vivo preclinical study illustrated maintenance of the high cushioning of the thermosensitive solutions. These results indicate that a CS/beta-GP system with optimal beta-GP concentration might be used as a submucosal injection agent in ESD, and further studies are needed to validate the effectiveness of the solutions in vivo.