Biocompatible Alginate–Chitosan Hybrid Hydrogels for Prolonged Nitric Oxide Release
Nitric oxide (NO) plays essential roles in angiogenesis, antimicrobial defense, and tissue repair, but its therapeutic application is hampered by rapid degradation and instability. Here, we present a biocompatible hybrid platform based on calcium-crosslinked alginate hydrogels incorporating chitosan nanoparticles (CSNPs) loaded with S-nitrosoglutathione (GSNO), an endogenous found NO donor. The materials were comprehensively characterized in terms of size distribution, chemical composition, morphology, thermal stability, viscoelastic behavior, and diffusion properties. CSNPs exhibited nanoscale dimensions with low polydispersity, while their incorporation into alginate matrices generated porous and thermally stable hydrogels with tunable viscoelasticity. UV-Vis monitoring of the hydrogel confirmed the sustained decomposition of GSNO over a period of 72 hours. In vitro release studies revealed that both free GSNO and GSNO-loaded CSNPs followed Higuchi kinetics, consistent with diffusion-driven transport; importantly, the nanoparticle-based hydrogel displayed a significantly prolonged release profile, reaching steady-state levels only after 6 h, in contrast to ~3 h for free GSNO. This slower and more sustained release maintained NO donor availability for up to 24 h. Cytocompatibility assays in HaCaT cells confirmed that all formulations were non-cytotoxic across therapeutically relevant concentrations. Together, these findings demonstrate that alginate–chitosan hybrid hydrogels constitute a biocompatible and versatile platform for prolonged NO delivery, with broad potential in biomedical applications.