Silk fibroin-coated resveratrol solid lipid nanoparticles for diabetic wound healing

Diabetic wounds remain a major clinical challenge due to delayed healing, persistent inflammation, and limited efficacy of existing therapies. Resveratrol possesses antioxidant, anti-inflammatory, and antibacterial properties but is restricted by poor solubility and rapid degradation. This study developed silk fibroin-coated resveratrol solid lipid nanoparticles (SF-RSLNs) to enhance resveratrol stability, provide controlled release, and improve therapeutic performance in diabetic wound healing. SF-RSLNs were fabricated using a microemulsion technique and optimized through a Box-Behnken design. The optimized nanoparticles exhibited a mean particle size of 222.1 nm, zeta potential of - 32 mV, entrapment efficiency of 85.7%, and drug loading of 10.2%. Characterization was performed using FTIR, SEM, and DLS analyses. In-vitro assessments included cytotoxicity (MTT), antioxidant activity (DPPH and ROS scavenging), antibacterial activity, scratch-wound healing, anti-inflammatory assays, and hemocompatibility evaluation. SF-RSLNs demonstrated sustained drug release (∼75% over 48 h), enhanced antioxidant activity (85% DPPH scavenging at 40 µg/mL), and significant wound closure (90% at 48 h). Antibacterial activity was improved, with inhibition zones of 18 mm against Staphylococcus aureus and 20 mm against Escherichia coli. SF-RSLNs also reduced TNF-α levels by 65% and increased IL-10 levels by 50%, while exhibiting excellent hemocompatibility. These findings indicate that SF-RSLNs serve as a multifunctional nanocarrier capable of enhancing resveratrol delivery and accelerating diabetic wound repair.