**1. Introduction**

Despite the advent of biologics, rheumatoid arthritis continues to be closely linked with pain, functional impairment, and depression, and a significant number of those with moderate to severe rheumatoid arthritis are too disabled to work several years after onset (Sokka et al., 1999). Furthermore, biologics have increased medical costs to nearly \$20,000/patient/year and side effects have hindered use by those with more advanced symptoms (Lundkvist et al., 2008). "Old" disease modifying anti-rheumatic drugs (DMARDs) are also linked to negative consequences as a result of non-specific organ toxicity. The exact cause of rheumatoid arthritis has not yet been identified and, consequently, treatment methods have not been optimally effective. Drug delivery systems may serve to reduce the necessary dosage and increase therapeutic efficacy of old and new rheumatoid arthritis treatments.

Numerous materials have been proposed as drug delivery systems for cancer, and, in recent years, the use of such materials has been increasingly extended to the treatment of rheumatoid arthritis. Liposomes, nanoparticles, micelles, and macromolecule-drug conjugates can be used to increase a drug's circulatory stability and thereby raise the probability for passive accumulation within the pannus, where permeability is enhanced. Both the specificity and therapeutic efficacy of these drug delivery systems can be further improved by combination with an active targeting moiety, such as an antibody, peptide, or polysaccharide that is specific for receptors concentrated on the surface of cells located within tissue affected by rheumatoid arthritis. The combination of passive and active targeting strategies can be used to optimize delivery of therapeutic agents to reduce toxicity and unwanted side effects and improve patient outcome. This chapter is intended to provide an overview of emerging techniques aimed at improving the efficacy of DMARDs, whilst simultaneously reducing the adverse consequences associated with non-specific targeting. Due to the nature of the disease, this review will focus only on drug delivery systems intended for systemic, rather than local/intra-articular, administration.
