Preparation of pH/temperature response P(DEA-AMPS-EGDMA) smart hydrogels for controlled release of 5-fluorouracil

5-fluorouracil (5-FU) is widely used in clinical chemotherapy, but its non-targeted delivery causes severe systemic toxicity, and uncontrolled burst release limits therapeutic efficacy. Existing pH/temperature-responsive hydrogels for 5-FU delivery suffer from low drug loading capacity and unbalanced sustained release performance, failing to meet clinical demands. To develop highly efficient and safe drug delivery carriers, this study employed a green aqueous solution radical polymerization method. Using DEA and AMPS as functional monomers and EGDMA as a crosslinking agent, a dual-response hydrogel PDAE responsive to both temperature and pH was synthesized. Performance testing demonstrated that this hydrogel exhibits excellent mechanical and swelling properties, along with good temperature/pH sensitivity. At a DEA/AMPS molar ratio of 121:9, the gel achieved maximum 5-FU loading capacity (326.84 mg·g−1) and encapsulation efficiency (16.72%). Under physiological conditions (37°C, pH 7.4), it exhibited a cumulative release rate of 26.34%, consistent with a first-order release model. Hemolysis rate <1.9% and cell viability >87.6% indicate favorable biosafety. The optimized hydrogel addresses the limitations of current 5-FU delivery systems, providing a promising smart carrier for clinical chemotherapy with improved targeting and reduced side effects.