Targeting the Arthritic Joint with Small Interfering RNA-Encapsulated Liposomes

Rheumatoid arthritis (RA) is characterized by chronic synovitis affecting multiple joints. Some forms of RA can be effectively treated with anti-TNF-α therapies. However, systemic treatment with anti-tumor necrosis factor-α (TNF-α) therapies can result in an impaired immune system and opportunistic infection; therefore, targeting therapies to the inflamed joints could avoid some of these systemic toxicities. Komano et al. evaluated the accumulation of small interfering RNA (siRNA)-encapsulated liposomes in inflamed joints and the therapeutic potential of these siRNA-encapsulated liposomes targeting TNF-α. Using a complex of the encapsulated liposome wrapsome (WS) and Cy5-labeled siRNA (siRNA/WS), higher fluorescence was observed in the inflamed joints versus normal tissues and in synoviocytes versus splenocytes/bone marrow/peripheral blood leukocytes. The majority of Cy5-positive synoviocytes were CD11b⁺, primarily macrophages and neutrophils. With the TNF-α targeting siRNA/WS, significant reductions in TNF-α mRNA and severity of the arthritis in the joints were observed. The siRNA/WS was mainly incorporated into CD11b⁺ cells, including macrophages and neutrophils, in the inflamed synovium, suggesting its potential therapeutic effects in RA by silencing the expression of inflammatory molecules produced by these cells in the joint and not systemically.

See article at J Pharmacol Exp Ther 2012, 340:109–113