Multifunctional Lactoferrin-coated Fusidic acid-loaded Zein nanoparticles for enhanced wound healing: A synergistic nanoplatform for tissue regeneration.

This study aimed to develop and characterize multifunctional lactoferrin-coated fusidic acid-loaded zein/dextran sulfate nanoparticles (LF-ZF-NPs) as an advanced nanoplatform for enhancing wound healing and tissue regeneration in chronic wounds. Zein and dextran sulfate (DS) were selected as core components due to their biocompatibility, biodegradability, excellent drug-loading capacity, and ability to enhance stability, solubility, and sustained release of fusidic acid (FA) while maintaining safe topical delivery. The formulation is designed to address the multifaceted challenges of chronic wounds, including bacterial infection, delayed healing, and suboptimal drug bioavailability, by exploiting the biological capabilities of zein, DS, FA and LF. ZF-NPs were synthesized via antisolvent precipitation and electrostatic deposition. The resulting NPs were spherical in shape, exhibited negative surface charge and excellent colloidal stability, with an encapsulation efficiency of 60.5 % at 10 % FA loading. In vitro release studies demonstrated sustained drug release over 72 h, especially in LF-ZF-NPs. The safety of LF-ZF-NPs was confirmed by their cytocompatibility on human dermal fibroblasts, and experiments in rats indicated an accelerated rate of wound healing. LF-ZF-NPs demonstrated anti-inflammatory and proliferative effects, as evidenced by the moderate expression of TNF-α and NF-κB. These findings highlight LF-ZF-NPs as a multifunctional and potent platform for advanced chronic wound treatment.