Biological and Life Sciences, School of Arts & Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad, Gujarat, 380009, India.
Biological Engineering Discipline, Indian Institute of Technology, IIT Gandhinagar, Palaj, Gujarat, 382355, India.
Adv Healthc Mater. 2024 Sep;13(22):e2400679. doi: 10.1002/adhm.202400679. Epub 2024 May 29.
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation and destruction. Current treatments, such as Methotrexate (MTX), though effective, often face limitations such as high plasma C and lack of sustained release. This study explores a synergistic approach to RA therapy using folate-liposomal co-delivery of MTX and RELA siRNA (short interfering RNA), targeting RAW264.7 macrophage repolarization via nuclear factor kappa B (NF-κB) pathway inhibition. Extensive in vitro characterizations demonstrate the stability and biocompatibility of this therapy via folate-liposomes. In the collagen-induced arthritis (CIA) rat model, treatment leads to reduced synovial inflammation and improved mobility. The combined MTX and RELA siRNA approach indirectly inhibits inflammatory cytokines, rheumatoid factor (RF), and C-reactive protein (CRP). Targeted macrophage delivery shows marked therapeutic effects in RAW264.7 murine macrophages, potentially modulating M1 to M2 polarization. This research presents a promising avenue for innovative RA therapies by inhibiting the inflammatory cascade and preventing joint damage.
类风湿性关节炎（RA）是一种慢性自身免疫性疾病，其特征为关节炎症和破坏。目前的治疗方法，如甲氨蝶呤（MTX），虽然有效，但往往面临着诸如高血浆 C 和缺乏持续释放等限制。本研究探讨了一种使用叶酸脂质体共递送 MTX 和 RELA siRNA（小干扰 RNA）的协同方法，通过抑制核因子 kappa B（NF-κB）通路来靶向 RAW264.7 巨噬细胞的极化。通过叶酸脂质体对这种治疗方法进行了广泛的体外特性分析，证明了其稳定性和生物相容性。在胶原诱导性关节炎（CIA）大鼠模型中，治疗可减轻滑膜炎症并提高运动能力。MTX 和 RELA siRNA 的联合应用可间接抑制炎症细胞因子、类风湿因子（RF）和 C 反应蛋白（CRP）。靶向巨噬细胞的递送在 RAW264.7 鼠巨噬细胞中显示出显著的治疗效果，可能调节 M1 向 M2 的极化。本研究通过抑制炎症级联反应和防止关节损伤，为创新性的 RA 治疗提供了一个有前途的途径。
