Preparation, Optimization, and Targeted Release of Chitosan Quaternary Ammonium Salt Thermosensitive Hydrogels

Abstract Chitosan (CS) exhibits a wide range of physicochemical properties in gel forms. In this work, the quaternized chitosan, N ‐[(2‐hydroxy‐3‐trimethylammonium)propyl] chitosan chloride (HTCC), was successfully synthesized and blended with CS and glycerophosphate (GP) to form a thermosensitive hydrogel. The HTCC exhibited a degree of quaternization of 78.52% and improved water solubility (5.7%, w/v). For a hydrogel composed of 1.57% CS, 0.23% HTCC, and 10% GP (w/v), the sol‐to‐gel transition occurred within 2 min at 40 °C. Notably, when the GP concentration reached approximately 6% (w/v), the CS‐HTCC‐GP hydrogel exhibited a unique biphasic behavior, transitioning from sol to gel either by cooling from room temperature to 5 °C or by heating to 40 °C. The NaCl release behavior of the CS‐HTCC‐GP hydrogel was influenced by both pH and temperature, with faster release observed under weakly basic conditions compared to neutral or acidic environments. The release process followed a quasi‐Fickian diffusion mechanism. These distinctive physicochemical properties suggest that the CS‐HTCC‐GP hydrogel holds great promise not only for controlled drug release applications but also for uses in hemostasis and embolization.