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<p>Rheumatoid arthritis is a chronic inflammatory disease characterized by progressive degeneration of joints and systemic complications. This study aimed at the development and evaluation of hydroxytyrosol-loaded solid lipid nanoparticles as a promising therapeutic approach against FCA-induced arthritis in rats. Hydroxytyrosol-loaded nanoparticles were prepared using stearic and lauric acids with Tween 80, showing a mean particle size of 109.7&#xa0;nm, a zeta potential of − 26.0 mV, and a high encapsulation efficiency (96.5%). In vitro antioxidant and anti-inflammatory activities were performed by total phenolic and flavonoid content, DPPH radical scavenging assay, hemolytic assay, and protein denaturation assay. The developed formulation was subjected to an in vivo study using 35 rats divided into seven groups. HT-NPs at a dose of 40&#xa0;mg/kg showed a significant reduction in arthritic score (0.78 ± 0.08) when compared to arthritic control (3.78 ± 0.08) and markedly decreased paw swelling (4.68 ± 0.13 vs. 5.92 ± 0.26). The treatment restored the oxidative balance by increased SOD (9.0 ± 0.2 U/mL) and CAT (66 ± 1.0 U/mL) and reduced MDA levels to 2.7 ± 0.10 nmol/mL. Further, HT-NPs treatment showed downregulation of pro-inflammatory and tissue-degrading genes such as TNF-α (1.30 ± 0.07 vs. 5.90 ± 0.16), IL-1β (1.50 ± 0.07 vs. 7.00 ± 0.16), and MMP-13 (2.12 ± 0.02 vs. 5.97 ± 0.08) while upregulating anti-inflammatory cytokines IL-10 and IL-4. The therapeutic potential of HT-NPs at high doses was comparable to methotrexate. These findings suggest that nanoencapsulation significantly enhances hydroxytyrosol’s therapeutic potential and thus support HT-NPs as a promising natural and safer alternative in the management of RA.</p>

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Hydroxytyrosol-encapsulated solid lipid nanoparticles mitigate induced arthritis via modulating the cytokines and MMP-13 expression and downregulating oxidative stress in rats

  • 期刊论文

  • 发表日期：

    2026年3月5日

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  • Noor ul Huda,
  • Aftab Ahmad,
  • Muhammad Anjum Zia,
  • Bushra Akhtar

摘要

Rheumatoid arthritis is a chronic inflammatory disease characterized by progressive degeneration of joints and systemic complications. This study aimed at the development and evaluation of hydroxytyrosol-loaded solid lipid nanoparticles as a promising therapeutic approach against FCA-induced arthritis in rats. Hydroxytyrosol-loaded nanoparticles were prepared using stearic and lauric acids with Tween 80, showing a mean particle size of 109.7 nm, a zeta potential of − 26.0 mV, and a high encapsulation efficiency (96.5%). In vitro antioxidant and anti-inflammatory activities were performed by total phenolic and flavonoid content, DPPH radical scavenging assay, hemolytic assay, and protein denaturation assay. The developed formulation was subjected to an in vivo study using 35 rats divided into seven groups. HT-NPs at a dose of 40 mg/kg showed a significant reduction in arthritic score (0.78 ± 0.08) when compared to arthritic control (3.78 ± 0.08) and markedly decreased paw swelling (4.68 ± 0.13 vs. 5.92 ± 0.26). The treatment restored the oxidative balance by increased SOD (9.0 ± 0.2 U/mL) and CAT (66 ± 1.0 U/mL) and reduced MDA levels to 2.7 ± 0.10 nmol/mL. Further, HT-NPs treatment showed downregulation of pro-inflammatory and tissue-degrading genes such as TNF-α (1.30 ± 0.07 vs. 5.90 ± 0.16), IL-1β (1.50 ± 0.07 vs. 7.00 ± 0.16), and MMP-13 (2.12 ± 0.02 vs. 5.97 ± 0.08) while upregulating anti-inflammatory cytokines IL-10 and IL-4. The therapeutic potential of HT-NPs at high doses was comparable to methotrexate. These findings suggest that nanoencapsulation significantly enhances hydroxytyrosol’s therapeutic potential and thus support HT-NPs as a promising natural and safer alternative in the management of RA.