Neuroprotective effects of protocatechuic acid-loaded carboxymethyl chitosan/oxidized xanthan gum Schiff’s base hydrogel

In clinical practice, traditional antioxidant drugs and therapies show limited efficacy against neurodegenerative diseases (NDs) induced by oxidative stress and excessive reactive oxygen species (ROS), underscoring the need for more effective treatments. In this work, we synthesized PCA-g-CMCS with vigorous antioxidant activity via an EDC/NHS-mediated system and confirmed that the graft retained the pH sensitivity of the precursor CMCS, enabling controllable dissolution across varying pH conditions. Subsequently, we prepared the Schiff’s base hydrogel PCA-g-CMCS/OXG by crosslinking PCA-g-CMCS with OXG at room temperature. The hydrogel significantly improved gel-forming performance, with mechanical/rheological properties matching nerve tissue and enhanced release behaviour, enabling prolonged and efficient drug delivery. Moreover, the hydrogel scaffold exhibited excellent biocompatibility and effectively protected nerve cells from H 2 O 2 -induced oxidative damage, highlighting its potential for neuroprotection. Thus, the PCA-g-CMCS/OXG hydrogel serves as a promising drug-loading platform, offering a potential therapeutic strategy for ROS-related NDs.