Biogenic Selenium Nanoparticle-Based Nanocomposite Hydrogel for Dual Delivery of Curcumin and Simvastatin for Topical Wound Healing Applications

Background: Chronic and ischemic wounds are dysregulated, causing inflammation, oxidative stress, and bacterial colonization. This work developed a bionanocomposite hydrogel using biogenic selenium nanoparticles (SeNPs) to encapsulate and topically distribute two weakly water-soluble medicines, curcumin (Curc) and simvastatin (SMV), to improve wound healing. Methods: Green production of biogenic SeNPs utilizing Psidium guajava (guava) leaf extract. Based on entrapment efficiency (%EE; E1) and cumulative drug release after 2 and 8 h (E2) and (E3), a two-factor, three-level Box–Behnken design selected the SeNP-to-drug weight ratio (C1) and ethanol concentration (C2). The selected nanoconstruct was integrated into a 2% w/v Carbopol 934 hydrogel and characterized by UV-vis, FTIR, SEM, and DLS. In a 14-day full-thickness excisional wound model in Wistar rats, wound contraction, tissue remodeling, inflammatory responses, and healing kinetics were examined to determine its therapeutic efficiency. Results: Formulation F9 had the highest overall attractiveness (0.998) and %EE values of 94.71% for SMV and 93.92% for Curc. DLS showed a hydrodynamic particle size of 177.7 nm and PDI of 0.41. Both medications were successfully incorporated without chemical incompatibility based on FTIR analysis. The selected nanogel maintained a skin-friendly pH of 6.2 ± 0.1 and sustained biphasic drug release. In vivo, the half-dose nanogel showed an enhanced wound-healing response, accelerating wound contraction and achieving complete epithelialization in 14 ± 1.06 days (p < 0.05) compared to 22 ± 2.5 days for the sham control, corresponding to a 36% reduction in healing time. Histopathology showed epidermal thickness restoration and well-organized collagen deposition. In addition, therapy dramatically decreased the proinflammatory biomarkers IL-1β, MMP-9, and COX-2 and increased IL-10 levels without causing tissue discomfort. Conclusions: The biogenic SeNP-based nanogel delivers Curc and SMV locally with prolonged drug release and anti-inflammatory and tissue-remodeling effects. The half-dose combination accelerated wound healing while retaining tissue compatibility, suggesting this green nanocomposite hydrogel could be a promising topical method for advanced cutaneous wound therapy.