LAUSR

Abstract Owing to their complex pathophysiology, diabetic wounds (DWs) pose serious challenges to current pharmacological modalities, eventually leading to high rate of amputation of lower extremities. This study aims to design novel hyaluronic acid (HA)-functionalized chitosan nanoparticles (CS-NPs) for efficient topical co-delivery of curcumin (CUR) and resveratrol (REV). Ionic-crosslinking technique was utilized for fabrication of HA functionalized co-loaded NPs (HA-CUR-REV-CS-NPs). Following a series of optimization and evaluations, HA functionalized NPs having optimum physicochemical characteristics (i.e., particle size  ± 30 mV, entrapment efficiencies of CUR and REV of ~90%) were fabricated. HA-functionalized CS-NPs exhibited good colloidal stability at room temperature (25 ± 2 °C) as well as in refrigerator (2–5 °C). The in vitro release studies revealed that HA-functionalized NPs followed Non-Fickian diffusion and sustained release mechanism. Conclusively, the resulting data evidenced that HA-functionalized co-loaded NPs might exhibit promising therapeutic potential for management of chronic DWs, therefore, further in vivo studies on diabetic animal model and acute and chronic toxicity studies are warranted.