Nanotherapeutic approaches for the treatment of rheumatoid arthritis

Advanced Review

Christine T. N. Pham

Published Online: Aug 11 2011

DOI: 10.1002/wnan.157

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Rheumatoid arthritis (RA) is a common inflammatory disease characterized by progressive bone and cartilage destruction, resulting in severe functional limitations, shortened lifespan, and increased mortality rates. Recent advances and new treatment approaches have significantly delayed disease progression and improved the quality of life for many patients. Yet few patients attain or can be maintained in disease remission without continuous immunosuppressive therapy. In addition, a sizable portion of patients also fails to respond or eventually develops tolerance to current therapies. Thus there is a continued need for the development of new therapeutic strategies for the treatment of RA. Unlike conventional drugs, nanosystems are designed to deliver therapeutic agents specifically to the site of inflammation, therefore avoiding potential systemic and off‐target unwanted effects. They allow investigators to consider or reconsider therapeutic agents that were previously deemed too toxic to deliver through a systemic route. This article reviews recent nanotechnology‐based strategies that are being developed for the treatment of inflammatory arthritis. WIREs Nanomed Nanobiotechnol 2011 3 607–619 DOI: 10.1002/wnan.157

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Figure 1.

Pathogenesis of rheumatoid arthritis (RA). In a genetically susceptible individual an environmental insult leads to a breach of immune tolerance, tipping the balance toward autoimmunity. This is usually heralded by the production of autoantibodies (rheumatoid factor, anti‐citrullinated protein antibody) by B cells with the help of T cells. Recruitment of activated T cells to the synovium leads to macrophage activation and the overproduction of inflammatory cytokines, including tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, and IL‐6. Cytokines also stimulate the proliferation of synovial fibroblasts, forming a pannus that is capable of invading cartilage and bone, leading to joint destruction. In addition, production of vascular endothelial growth factor (VEGF) by synovial fibroblasts and other cells stimulate angiogenesis, which perpetuates the inflammation by recruiting more inflammatory leukocytes. Growth of the pannus also induces a state of relative hypoxia that further promotes angiogenesis through the elaboration of hypoxia‐inducible factor (HIF)‐1.

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works at the interface of biotechnology and materials science. His lab is researching many topics, such as investigating the mechanism of release from polymeric delivery systems with concomitant microstructural analysis and mathematical modeling; studying applications of these systems including the development of effective long-term delivery systems for insulin, anti-cancer drugs, growth factors, gene therapy agents and vaccines; developing controlled release systems that can be magnetically, ultrasonically, or enzymatically triggered to increase release rates; synthesizing new biodegradable polymeric delivery systems which will ultimately be absorbed by the body; creating new approaches for delivering drugs such as proteins and genes across complex barriers such as the blood-brain barrier, the intestine, the lung and the skin; stem cell research including controlling growth and differentiation; and creating new biomaterials with shape memory or surface switching properties.

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