Polyelectrolyte composite hydrogels based on a derivative of functional dietary fiber for long-term gastric retention and drug delivery

Gastric retention drug delivery is experiencing significant demand for hydrogels that exhibit in situ controllable forming in the stomach, resistance against severe gastric degradation, and exceptional biocompatibility. However, current studies lack comprehensive investigations on these requirements. In this study, resistant starch is chosen as a kind of novel dietary fiber with remarkable gastric retention effects compared to conventional natural polymers. To address its limited solubility, resistant starch was modified by carboxymethyl groups. Moreover, a semi-dissolution acidification sol–gel transition method was employed to enable in situ gelation under gastric acid conditions and fabricate physically crosslinked polyelectrolyte composite hydrogels (CMRS/CTS) based on carboxymethylated resistant starch and chitosan. This method obviates the need for toxic chemical crosslinkers and initiators, ensuring favorable biocompatibility. The influence of carboxymethyl substitution degree and the anion-to-cation ratio of the composite hydrogels on the mechanical, rheological, and swelling properties was thoroughly investigated. Compared to conventional carboxymethyl starch-based hydrogels, CMRS/CTS maintained a relatively intact structure even after immersion in simulated gastric fluid for 30 days owing to the enzymatic stability of the hydrogel. Upon drug loading, CMRS/CTS exhibited sustained and controlled drug release, facilitating prolonged therapeutic effects. Simultaneously achieving in situ gastric drug release, biocompatibility, resistance to degradation, and sustained release, CMRS/CTS represents a promising avenue for the development of long-term gastric retention hydrogels.