<scp>pH</scp> ‐Sensitive Nanocomposite Based on Mesoporous Silica Nanoparticle–Alginate Hydrogels for Local Administration of Tetracycline Hydrochloride

ABSTRACT Silica nanoparticle (Si NP)/alginate hydrogel (Al Hyd) nanocomposites loaded with tetracycline hydrochloride (Tc) were developed and evaluated as pH‐responsive wound dressing systems. Al Hyds were cross‐linked using either calcium chloride (Ca) or glutaraldehyde (Glu). Tc‐loaded Si NPs were synthesized via a sol–gel method in the presence of Tc and subsequently incorporated into the Al Hyd matrix. The morphology and chemical structure of the composites were characterized using SEM and FTIR analyses. Entrapment of Tc during Si NP synthesis resulted in high drug loading efficiencies of 91.79% and 93.33% for 20 and 40 wt% formulations. Drug release studies revealed a slow and strongly pH‐dependent release behavior. At pH 7.4, Tc@Si NPs–Al Hyd/Ca and Tc@Si NPs–Al Hyd/Glu released 67% and 43% of Tc within 8 h, whereas at pH 5.6 the release decreased to 33% and 23%. Cytotoxicity assays showed no toxic effects on normal fibroblast cells. Based on superior release performance, the Ca‐cross‐linked system was selected for antibacterial evaluation and showed strong activity, producing inhibition zones of 12.65 mm against E. coli and 30.46 mm against S. aureus . These results highlight the potential of pH‐sensitive alginate/Si NP nanocomposite hydrogels for controlled antibiotic delivery in advanced wound dressing applications.