Macrophage targeted tuftsin-modified alginate nanoparticles as non-viral delivery system for anti-inflammatory gene therapy in the treatment of rheumatoid arthritis

• Online Access: http://hdl.handle.net/2047/D20204485

The goal of this project is to develop and characterize a macrophage targeted alginate polymer based gene delivery system for the treatment of rheumatoid arthritis in Male Lewis Rats. The idea behind developing such a system has been based on the central role of macrophages in inflammation and particularly, in the pathogenesis of rheumatoid arthritis (RA). The main function of macrophages over there is to secrete pro-inflammatory cytokines such as TNF- and IL-1. Additionally, macrophages are capable of sustaining processes such as angiogenesis and are also involved in the remodeling of the local tissue by secreting various enzymes. All these plethora of events then lead to erosion of joint space, pannus formation, cartilage and bone destruction-some of the common manifestations of rheumatoid arthritis. Therefore, targeting macrophages is considered as a rational approach for anti-inflammatory based therapies. Towards that end, IL-10 encoding cytokine was encapsulated into a macrophage-targeted nanoparticles and the efficacy of the system was tested in a robust model of rheumatoid arthritis. The results demonstrated that targeting macrophages not only resulted in a reversal of macrophage phenotype from a pro-inflammatory state to anti-inflammatory state but also the treated animals were able to retain their mobility for extended period of time. Overall, this study provides preliminary evidence for safe and effective non-viral gene delivery strategy targeting macrophages for effective treatment of inflammatory diseases such as RA.