Salmon bone-derived chondroitin sulfate nanogels for controlled delivery of curcumin: release behavior, structural characteristics and anti-inflammatory efficacy.

Marine-derived polysaccharides have emerged as sustainable biomaterials for advanced drug delivery; however, the relationship between their molecular organization and drug release behavior remains insufficiently understood. In this study, chondroitin sulfate (CS) extracted from salmon bone was utilized to fabricate Ca2+-crosslinked nanogels for the controlled delivery of curcumin (Cur). The optimized nanogels exhibited a hydrodynamic diameter of 217.3 ± 15.6 nm, a polydispersity index of 0.25 ± 0.02, and a negative zeta potential of -26.9 ± 0.14 mV, indicating good colloidal stability. Comprehensive structural characterization via FT-IR and XRD indicated that the nanogel framework is stabilized by Ca2+-mediated ionic crosslinking and multi-point hydrogen bonding. Notably, XRD analysis revealed that while encapsulated curcumin primarily adopts an amorphous molecular dispersion, the emergence of a specific reflection at 2θ ≈ 14° suggests that a minor fraction adopts a locally ordered state stabilized within the nanogel microenvironment. The nanogels demonstrated a sustained biphasic release profile governed by anomalous (non-Fickian) diffusion (n = 0.711). Furthermore, in LPS-stimulated RAW 264.7 macrophages, the CS-Cur nanogels showed significantly enhanced anti-inflammatory efficacy and high biocompatibility compared to free curcumin. These findings highlight salmon bone-derived CS as a sustainable, high-performance matrix for hydrophobic drug delivery, providing new insights into the role of cargo-induced structural organization in regulating therapeutic release and biological performance.