Mannose-decorated N-succinyl chitosan nanoparticle film: A novel approach for enhanced wound healing

Chronic and non-healing wounds remain a major healthcare challenge, necessitating advanced therapeutic systems that promote rapid repair while preventing infections. In this study, we fabricated and evaluated mannose-conjugated N-succinyl chitosan nanoparticles (M-N-SuC NPs) embedded in a polymeric film for targeted wound healing. Mannose functionalization was incorporated to potentially facilitate interaction with macrophages, as reported for similar systems, while N-succinyl chitosan served as a biodegradable carrier for hesperidin (HPN), a natural flavonoid with angiogenic, antioxidant, and anti-inflammatory properties. The NPs were synthesized via ionic gelation and incorporated into a sodium alginate/polyvinyl alcohol/hyaluronic acid (SA/PVA/HA) film using solvent casting. The optimized NPs displayed a uniform spherical morphology with an average size of 205.2 ± 8.4 nm, a zeta potential of -30.98 ± 2.6 mV, and high entrapment efficiency (96.31 ± 2.4 %). In vitro drug release demonstrated a sustained profile with 69.45 % cumulative release over 24 h. Hemocompatibility assays showed minimal hemolysis, confirming safety. Ex vivo permeation studies demonstrated 3-fold higher skin penetration compared to free HPN, corroborated by confocal imaging showing deeper epidermal deposition. In vivo wound healing in Wistar rats demonstrated 97.89 ± 1.48% wound contraction by day 14, accompanied by marked collagen deposition and rapid re-epithelialization. These findings demonstrate that the mannose-conjugated nanoparticle film functions as a safe and multifunctional platform for controlled delivery and accelerated tissue regeneration, supported by enhanced drug permeation and in vivo wound healing performance.