pH‐Responsive Polyacrylic Acid Hydrogels Cross‐Linked with Functionalized Collagen Peptide for Controlled Drug Release

Abstract Crosslinkers play a crucial role in hydrogel preparation, influencing key properties such as mechanical strength, swelling behavior, and biocompatibility. However, most conventional crosslinkers exhibit poor biocompatibility, with some inducing significant cytotoxicity that limits their biomedical applications. The development of nontoxic crosslinkers with excellent biocompatibility and high safety can be expected to resolve this issue. In this work, a series of poly(acrylic acid) hydrogels using modified collagen peptide as bio‐crosslinkers were synthesized through in situ UV irradiation polymerization. An interconnected porous architecture was observed by scanning electron microscopy, and marked pH‐dependent swelling behavior was found by swelling kinetics analysis. Thermogravimetric analysis and mechanical testing confirmed superior thermal stability and mechanical properties. Under simulated gastrointestinal conditions, amoxicillin and ibuprofen exhibited distinct pH‐responsive release behaviors: less than 40% release in simulated gastric fluid (pH 1.2) after 16 h, compared to over 85% in simulated intestinal fluid (pH 7.4), confirming effective drug delivery control. The kinetics of drug release followed the Non‐Fickian diffusion mechanism (Korsmeyer–Peppas model). Hemocompatibility tests and cytotoxicity assays validated the excellent biocompatibility. These findings show the modified collagen peptide cross‐linked poly(acrylic acid) hydrogels’ potential as advanced oral drug delivery carriers.