Title : Lutein–acacia nanoparticle-loaded alginate hydrogel for accelerated wound healing and scar reduction

Chronic wounds remain a major global healthcare challenge due to persistent inflammation, oxidative stress, and impaired extracellular matrix remodeling. Lutein (LUT), a xanthophyll carotenoid with potent antioxidant and anti-inflammatory properties, has shown therapeutic promise in wound healing; however, its clinical use is limited by poor aqueous solubility and low skin permeability. This study aimed to develop and optimize a lutein–acacia gum–sodium alginate (LUT–ACC–SA) nanoparticle-loaded hydrogel for enhanced topical delivery and accelerated wound healing.

LUT–ACC nanoparticles were prepared through adsorption and ionic gelation techniques and subsequently incorporated into a sodium alginate hydrogel matrix. A Box–Behnken design was applied to optimize formulation parameters, including acacia concentration, sodium alginate concentration, and calcium chloride concentration. The optimized formulation contained 1.0 mg/mL LUT, 12.2 mg/mL ACC, and 2.5% sodium alginate, producing nanoparticles with a particle size of 118.5 ± 3.2 nm, zeta potential of −32.8 ± 1.1 mV, and a polydispersity index of 0.218 ± 0.01. The formulation was further characterized using DSC, FT-IR, XRD, SEM, and rheological analysis.

In vitro release studies demonstrated sustained release of lutein from the nanoparticleloaded hydrogel. In vivo wound healing efficacy was evaluated using a full-thickness excisional wound model in rats. Animals treated with the LUT–ACC–SA nanoparticleloaded hydrogel showed significantly enhanced wound closure compared with control groups, achieving 41.6% ± 2.8 closure by day 3 and 99.6% ± 1.1 closure by day 14 (p < 0.05–0.001). Biochemical analysis further demonstrated reduced inflammatory response, evidenced by lower IL-6 levels, along with significant increases in VEGF, TGF-β1, and collagen I expression, indicating improved angiogenesis and extracellular matrix remodeling.

The findings suggest that the LUT–ACC–SA nanoparticle-loaded hydrogel represents a promising topical delivery platform for chronic wound management by combining sustained release, antioxidant protection, anti-inflammatory activity, and enhanced tissue regeneration.

Samaa Abdullah is a researcher affiliated with the Faculty of Pharmacy at Applied Science Private University, Jordan, and a member of the Innovative NanoBioTech & Translational Drug Delivery Research Group. Her research focuses on nanotechnologybased drug delivery systems, biomaterials, wound healing formulations, and translational pharmaceutical sciences. She has contributed to research involving nanoparticle-loaded hydrogels and advanced topical therapeutic systems for improving tissue regeneration and controlled drug delivery.