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Joint-Targeting Drug Delivery System for Rheumatoid Arthritis: siRNA Encapsulated Liposome

Yukiko Komano, Nobuhiro Yagi and Toshihiro Nanki

Rheumatoid Arthritis (RA) is characterized by persistent inflammation in multiple joints. Uncontrolled active RA causes disability, decreases quality of life, and increases comorbidity. Over the past two decades, the importance of aggressive treatment as early as possible has been emphasized to improve outcomes, and, most importantly, inhibit the destruction of joints. RNA interference, mediated by small interfering RNA (siRNA), is a powerful method used to silence genes with a high degree of specificity. Developing a means to deliver siRNA via a systemic injection to multiple affected joints is of importance for applying this technology to the treatment of RA. A recent study showed that a wrapsome (WS), which was designed with a core composed of a cationic lipid bilayer and siRNA complex enveloped in a neutral lipid bilayer with polyethylene glycol on the surface, could be a potential vehicle for siRNA delivery for the treatment of arthritis. The complex of siRNA and WS (siRNA/WS) selectively accumulated in the inflamed synovium. Furthermore, treatment with siRNA-targeting tumor necrosis factor-α/WS ameliorated arthritis in a murine model. In this manuscript, we review potential of siRNA as a therapeutic tool for rheumatoid arthritis.