Thermoresponsive Amifostine-Loaded Chitosan Biogel for Prevention of Radiation-Induced Rectal Injury

Abstract

Radiation-induced rectal injury (RRI) limits radiotherapy and results in a poor clinical prognosis. In this study, we report a radioprotective strategy for preventing RRI using a thermoresponsive amifostine-loaded chitosan biogel. Specifically, the biogel is synthesized via the reaction of crocetin with cysteine-modified chitosan and sodium alginate, followed by incorporating amifostine−sodium glycerophosphate solution. The storage modulus increases markedly at the gel point of ∼30 °C. The biogel possesses favorable biocompatibility in vitro and maintains the ability of cells to migrate and proliferate after 8 Gy irradiation. Meanwhile, it possesses good stability in artificial intestinal fluid and can slowly release amifostine for more than 12 h. With the aid of endoscopy, the biogel can be precisely delivered to the colorectal region and alleviates RRI by promoting mucosal recovery, enhancing crypt activity, and modulating inflammation. In addition, the biogel shows a trend toward increasing the abundance of gut flora and the counts of probiotics, thereby maintaining gut microbial homeostasis. This work provides a simple yet transformative tactic by the thermoresponsive biogel, and presents a promising avenue for clinical prevention of RRI.