Development of pH-Responsive SA/PEGDA/AS-POSS Hydrogels via Michael Addition for Controlled Drug Release and Enhanced Mechanical Properties.

In this study, thiolated sodium alginate (SA) and hydrophilic, polymerizable Janus-type polyhedral oligomeric silsesquioxane (AS-POSS) are synthesized by introducing thiol and sulfonic acid groups, respectively. A series of pH-responsive SA/PEGDA/AS-POSS nanocomposite hydrogels are successfully prepared through Michael addition reactions between the thiol groups of thiolated sodium alginate and the double bonds in the molecular chains of AS-POSS and poly(ethylene glycol) diacrylate (PEGDA). This reaction proceeds rapidly under physiological conditions without requiring initiators or catalysts. As the content of AS-POSS increases, the pore size within the hydrogel decreases, and the network structure becomes denser, with significant improvements in mechanical properties. The hydrogel exhibits excellent pH sensitivity, showing lower swelling in acidic media compared to neutral media, and undergoing hydrolysis and losing stability in alkaline media. Moreover, the incorporation of AS-POSS significantly enhances the drug-loading capacity (85.7 %) and encapsulation efficiency (72.1 %) of doxorubicin (DOX). The drug is released faster in weakly acidic environments, with a cumulative release rate reaching 80.4 %, demonstrating excellent targeting and controlled release properties. Cytotoxicity tests show that the SA/PEGDA/AS-POSS hydrogel has good biocompatibility and exhibits effective tumor-killing ability, indicating its great potential as a drug carrier with promising applications in biomedical materials.