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 <200 nm, zeta potential > ± 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.

由于其复杂的病理生理学，糖尿病伤口（DWs）对当前的药理学形式提出了严峻挑战，最终导致下肢截肢率高。这项研究旨在设计新型的透明质酸（HA）-功能化的壳聚糖纳米颗粒（CS-NPs），以有效地局部递送姜黄素（CUR）和白藜芦醇（REV）。离子交联技术用于制造HA功能化的共载NP（HA-CUR-REV-CS-NP）。经过一系列的优化和评估，制造出具有最佳理化特性（即，粒径<200 nm，ζ电势>±30 mV，CUR和REV的包封效率为〜90％）的HA官能化NP。HA官能化的CS-NP在室温（25±2°C）以及冰箱（2-5°C）中均表现出良好的胶体稳定性。体外释放研究表明，HA功能化的NPs遵循非菲克扩散和持续释放机制。结论是，所得数据证明，HA功能化的共载NP可能显示出有潜力治疗慢性DW，因此，有必要对糖尿病动物模型进行进一步的体内研究，并进行急性和慢性毒性研究。