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SP0050 Nanomedicine Approaches in Rheumatology

Rheumatoid arthritis (RA) is one of the most common and severe autoimmune diseases related to joints [1, 2]. Regrettably, RA inflammatory process remains puzzling, and finding effective therapies for the disease as well as new means for its early diagnosis have been daunting tasks. As a response to RA inflammation, the synovial tissue shows synovial lining hyperplasia as a result of Fibroblast-Like Synoviocyte (FLS) and Macrophage-Like Synoviocyte (MLS) accumulation. In fact, the synovial intimal lining in RA, instead of one or two cells deep, is frequently up to five-fold deeper. Consequently, more macrophages, lymphocytes, and fibroblasts are activated and the RA inflammatory process remains [2–4]. Thus, macrophages play a pivotal role in the features and progress of RA, and effective diagnosis and therapy may encompass the ability to target these cells. Currently, the main target of RA therapy is to control the inherent inflammatory response and alleviate pain. Several therapeutic options have been used to manage and slow down the progression of the disease, which include the use of sulfasalazine, hydroxychloroquine or methotrexate – a first line disease modifying anti-rheumatic drug (DMARD) [5, 6]. Methotrexate (MTX), is being widely used due to its satisfactory safety profile, efficacy and low cost. It is an analogue of folic acid as it disrupts cellular folate metabolism by inhibiting its target enzyme, dihydrofolate reductase [6–8]. Still, there is a lack of specificity for MTX and/or other similar drugs. Nanomedicine has thrived and is now providing new possibilities for the use of nanomaterials in medical applications for drug delivery and tissue regeneration [9–11]. Recent developments in the understanding of inflammation have led to an increased interest in the use of nanomedicine in the treatment of rheumatoid arthritis. Nanomedicine may also offer new opportunities to combine diagnosis and therapy in a single approach. Improved theranostics processes are being studied in order to develop new means to diagnose, fight and follow disease. The release and action of anti-rheumatic drug may be enhanced and controlled, and potentially without injuring healthy tissues and organs, while simultaneously providing a non-invasive and specific imaging tool for RA. This presentation aims at explaining the major applications of nanomedicine in rheumatoid arthritis treatment and diagnosis. Commercial successes of RA active targeting of nanomedicine and products under development will be revised. Insights on multifunctional anti-CD64 mAb-modified nanoparticles for the combined delivery of MTX and iron oxide nanoparticles (SPIONs) proposed by our group will be presented [12, 13]. Proposed nanoparticles have the potential to provide a new theranostic approach for RA management. References Davis Iii JM, Matteson EL. My Treatment Approach to Rheumatoid Arthritis. Mayo Clinic Proceedings. 2012;87:659–73. Firestein GS. Etiology and pathogenesis of rheumatoid arthritis. Kelley's Textbook of Rheumatology. 7th ed2005. Liu H, Pope RM. The role of apoptosis in rheumatoid arthritis. Current opinion in pharmacology. 2003;3:317–22. Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. The New England journal of medicine. 2001;344:907–16. Firth J. Treating to target in rheumatoid arthritis. Nurse Prescribing. 2007;10:293–302. Chen YT, C; Huang, P; Chang, M; Cheng, P; Chou, C; Chen, D; Wang, C; Shiau, A; Wu, C. Methotrexate conjugated to gold nanoparticles inhibits tumor growth in a syngeneic lung tumor model. Molecular Pharmacology. 2007;4:713–22. Tian H, Cronstein BN. Understanding the mechanisms of action of methotrexate: implications for the treatment of rheumatoid arthritis. Bulletin of the NYU hospital for joint diseases. 2007;65:168–73. Yazici Y, Sokka T, Kautiainen H, Swearingen C, Kulman I, Pincus T. Long term safety of methotrexate in routine clinical care: discontinuation is unusual and rarely the result of laboratory abnormalities. Annals of the rheumatic diseases. 2005;64:207–11. Andresen T, Thompson D, Kaasgaard T. Enzyme-triggered nanomedicine: drug release strategies in cancer therapy. Molecular membrane biology. 2010;27:353–63. Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Advanced drug delivery reviews. 2003;55:329–47. Ferrari M. Cancer nanotechnology: opportunities and challenges. Nature Reviews Cancer. 2005;5:161–71. Moura CC, Segundo MA, Neves J, Reis S, Sarmento B. Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application. Int J Nanomedicine. 2014;9:4911–22. Albuquerque J, Moura CC, Sarmento B, Reis S. Solid Lipid Nanoparticles: A Potential Multifunctional Approach towards Rheumatoid Arthritis Theranostics. Molecules. 2015;20:11103–18. Disclosure of Interest None declared