Guar gum macromolecule-based nanoformulation of syringic acid for enhanced diabetic wound healing: Box-Behnken...

Diabetic wound healing is impaired by persistent oxidative stress, reduced angiogenesis, and delayed tissue regeneration. In this study, a guar gum-based nanoformulation of syringic acid (NF) was developed and optimized using a Box-Behnken design to improve physicochemical characteristics and in vitro biological performance. The optimized NF exhibited a mean particle size of ~26 nm, low polydispersity (PDI) (~0.1), a negative zeta potential (-27.6 mV), high encapsulation efficiency (~83%), and spherical morphology. Thermal and spectroscopic analyses confirmed successful drug incorporation and enhanced stability. In vitro release studies indicated a diffusion-controlled, sustained-release profile. Compared with free syringic acid, NF demonstrated enhanced antioxidant activity, improved α-glucosidase and α-amylase inhibition, and improved cytocompatibility in L929 fibroblasts and HaCaT keratinocytes. Under hyperglycaemic conditions, NF significantly reduced lipid peroxidation and restored the activities of endogenous antioxidant enzymes, i.e., superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST). The formulation also promoted keratinocyte migration (81.6% wound closure) and enhanced endothelial tube formation, accompanied by increased VEGF expression (71.61% VEGF-positive cells). Overall, nanoencapsulation improved the functional activity of syringic acid under diabetic-like conditions. These findings provide an in vitro foundation for future mechanistic and in vivo investigations in wound-related models.