<p>Chronic wounds are a global health issue due to persistent inflammation, oxidative stress, and impaired extracellular matrix remodelling. Lutein, a xanthophyll carotenoid with antioxidant and anti-inflammatory properties, holds therapeutic promise but suffers from poor solubility and skin permeability. To overcome these limitations, a lutein–acacia gum–sodium alginate (LUT–ACC–SA) nanoparticle-loaded hydrogel was developed to enhance topical delivery and accelerate wound healing. Nanoparticle-loaded hydrogels were formulated via ionic gelation and optimised for particle size, zeta potential, and polydispersity index. The statistically optimised nanogel system was developed using Box–Behnken design (1.0&#xa0;mg/mL LUT, 12.2&#xa0;mg/mL ACC, 2.5% SA), which showed a particle size of 118.5 ± 3.2&#xa0;nm, zeta potential of − 32.8 ± 1.1 mV, and PDI of 0.218 ± 0.01. Characterisation included DSC, FT-IR, XRD, and SEM. In vitro release, rheology, and stability were evaluated. In vivo, full-thickness excisional wounds in rats (<i>n</i> = 9/group) were treated with control, blank ACC–SA gel, LUT–SA gel, or LUT–ACC–SA nanoparticle-loaded hydrogel. Wound closure was assessed on days 3, 7, and 14, alongside ELISA analysis of VEGF, TGF-β1, collagen I, and IL-6 in tissue homogenates. The nanoparticle-loaded hydrogel group showed significantly faster healing: 41.6% ± 2.8 closure by day 3 and 99.6% ± 1.1 by day 14, compared to controls (<i>p</i> &lt; 0.05–0.001). It also markedly reduced IL-6 (19.6 ± 0.8 ng/mL) and increased VEGF (13.2 ± 0.7 ng/mL), TGF-β1 (24.6 ± 0.9 ng/mL), and collagen I (26.1 ± 0.9 ng/mL). These findings support LUT–ACC–SA nanoparticle-loaded hydrogel as a promising wound-healing formulation through modulation of inflammation, angiogenesis, and matrix remodelling.</p> Graphical abstract <p></p>

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Lutein–Acacia Nanoparticle-Loaded Alginate Hydrogel for Accelerated Wound Healing and Scar Reduction

  • Samaa Abdullah,
  • Samar Thiab,
  • Abeer A. Altamimi,
  • Alaa A. Al-Masud,
  • Meshal Marzoog Al-Sharafa

摘要

Chronic wounds are a global health issue due to persistent inflammation, oxidative stress, and impaired extracellular matrix remodelling. Lutein, a xanthophyll carotenoid with antioxidant and anti-inflammatory properties, holds therapeutic promise but suffers from poor solubility and skin permeability. To overcome these limitations, a lutein–acacia gum–sodium alginate (LUT–ACC–SA) nanoparticle-loaded hydrogel was developed to enhance topical delivery and accelerate wound healing. Nanoparticle-loaded hydrogels were formulated via ionic gelation and optimised for particle size, zeta potential, and polydispersity index. The statistically optimised nanogel system was developed using Box–Behnken design (1.0 mg/mL LUT, 12.2 mg/mL ACC, 2.5% SA), which showed a particle size of 118.5 ± 3.2 nm, zeta potential of − 32.8 ± 1.1 mV, and PDI of 0.218 ± 0.01. Characterisation included DSC, FT-IR, XRD, and SEM. In vitro release, rheology, and stability were evaluated. In vivo, full-thickness excisional wounds in rats (n = 9/group) were treated with control, blank ACC–SA gel, LUT–SA gel, or LUT–ACC–SA nanoparticle-loaded hydrogel. Wound closure was assessed on days 3, 7, and 14, alongside ELISA analysis of VEGF, TGF-β1, collagen I, and IL-6 in tissue homogenates. The nanoparticle-loaded hydrogel group showed significantly faster healing: 41.6% ± 2.8 closure by day 3 and 99.6% ± 1.1 by day 14, compared to controls (p < 0.05–0.001). It also markedly reduced IL-6 (19.6 ± 0.8 ng/mL) and increased VEGF (13.2 ± 0.7 ng/mL), TGF-β1 (24.6 ± 0.9 ng/mL), and collagen I (26.1 ± 0.9 ng/mL). These findings support LUT–ACC–SA nanoparticle-loaded hydrogel as a promising wound-healing formulation through modulation of inflammation, angiogenesis, and matrix remodelling.

Graphical abstract