Preparation of cationic liposomes loaded with Sirtuin 6 plasmid for the treatment of arthritis in rats

Arthritis, ormalizedn by chronic joint inflammation, is increasingly prevalent due to global ageing, placing significant pressure on healthcare systems. Recent studies have identified Sirtuin 6 (Sirt6) as a promising therapeutic target for alleviating arthritis symptoms. This study investigates the therapeutic potential of Sirt6-loaded cationic liposomes in a collagen-induced arthritis (CIA) rat model. Sirt6-loaded cationic liposomes were prepared and ormalizedn using transmission electron microscopy, particle size distribution, polydispersity index (PDI), zeta potential, encapsulation efficiency, in vitro release, and stability studies. The optimal Sirt6 plasmid-to-liposome ratio was established at 1:1000. Characterisation 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 h. In vitro, the endocytosis of Sirt6-loaded liposomes significantly increased Sirt6 protein expression in chondrocytes (p In vivo, treatment reduced inflammation in liver and spleen tissues and lowered pro-inflammatory cytokines associated with CIA (p Sirt6-loaded liposomes as a potential novel therapeutic strategy for treatment of arthritis.

关节炎以慢性关节炎症为核心病理表现，伴随全球人口老龄化进程加剧，其发病率逐年攀升，给全球医疗保健系统带来了沉重压力。近期研究已将沉默信息调节因子6（Sirtuin 6, Sirt6）确定为缓解关节炎症状的极具潜力的治疗靶点。本研究针对负载Sirt6的阳离子脂质体在胶原诱导性关节炎（CIA）大鼠模型中的治疗潜力展开系统探究。
研究人员首先制备了负载Sirt6的阳离子脂质体，并通过透射电子显微镜、粒径分布、多分散指数（PDI）、ζ电位、包封率、体外释放实验及稳定性考察对其进行表征。实验确定最优的Sirt6质粒与脂质体配比为1:1000。表征结果证实，该脂质体呈均匀球形形貌，粒径为177.65 ± 2.09 nm，多分散指数为0.216 ± 0.013，ζ电位为21.78 ± 1.76 mV。该脂质体展现出优异的释放特性与储存稳定性，可维持结构完整性长达30天，并在24小时内实现90.77 ± 3.35%的包封药物释放率。体外实验表明，负载Sirt6的脂质体通过内吞作用可显著提升软骨细胞内Sirt6蛋白的表达水平（p < 0.05）。体内实验中，该治疗制剂可减轻肝、脾组织的炎症反应，并降低与CIA相关的促炎细胞因子水平（p < 0.05）。综上，负载Sirt6的阳离子脂质体有望成为治疗关节炎的新型潜在治疗策略。