Activated macrophages play an important role in the initiation and development of inflammatory diseases. The aim of this study is to develop a delivery system that targets siRNA to activated macrophages. Exploiting the presence of folate receptors on the surface of activated macrophages, folic acid was conjugated to chitosan (FA-CS) and used to formulate siRNA into nanoparticles capable of cell specific delivery. The physiochemical properties of the nanoparticles, including size, zeta-potential and encapsulation efficiency, were characterized and the intracellular uptake and gene silencing efficiency were studied in vitro. The results showed that folic acid conjugation enhanced cellular uptake and silencing effect in activated macrophages. An in vivo biodistribution analysis, performed in a subcutaneous inflammation model, confirmed targeting of FA-CS/siRNA to inflamed tissue. The results indicate that FA-CS can be a potential siRNA carrier for anti-inflammatory therapy.
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