Preparation of Cationic Liposomes Loaded with Sirtuin 6 Plasmid for the Treatment of Arthritis in Rats

Arthritis, characterized by chronic joint inflammation, is increasingly prevalent due to global aging, placing significant pressure on healthcare systems. Recent studies have identified Sirtuin 6 (<i>Sirt6</i>) as a promising therapeutic target for alleviating arthritis symptoms. This study investigates the therapeutic potential of <i>Sirt6</i>-loaded cationic liposomes in a collagen-induced arthritis (CIA) rat model. <i>Sirt6</i>-loaded cationic liposomes were prepared and characterized using transmission electron microscopy, particle size distribution, polydispersity index (PDI), zeta potential, encapsulation efficiency, in vitro release, and stability studies. The optimal <i>Sirt6</i> plasmid-to-liposome ratio was established at 1:1000. Characterization confirmed a spherical morphology, with a particle size of 177.65 ± 2.09 nm, a PDI of 0.216 ± 0.013, and zeta potential of 21.78 ± 1.76 mV. The liposomes exhibited superior release profiles and storage stability, thus maintaining their integrity for up to 30 days and achieving 90.77 ± 3.35% release efficiency within 24 hours. <i>In vitro</i>, the endocytosis of <i>Sirt6</i>-loaded liposomes significantly increased <i>Sirt6</i> protein expression in chondrocytes (<i>P</i> &lt; 0.01). <i>In vivo</i>, treatment reduced inflammation in liver and spleen tissues and lowered pro-inflammatory cytokines associated with CIA (<i>P</i> &lt; 0.01). These findings support <i>Sirt6</i>-loaded liposomes as a potential novel therapeutic strategy for treatment of arthritis.