Combination drug delivery approaches in rheumatoid arthritis

Rheumatoid arthritis is one of the most common inflammatory autoimmune disorders which is often characterized by pain, inflammation in joints, bone, and cartilage degradation along with cardiovascular, pulmonary, and skeletal disorders. Although the etiology behind the diseases is still unknown several factors such as the proinflammatory cytokines, interleukins, macrophages, etc., are responsible for the induction of inflammation. Therefore drugs that either reduce inflammation or target these factors have been utilized as RA therapy. The role of genes and RNAi have also been explored to limit the toxicity issues related to these drugs. siRNA and miRNA play an important role by upregulating and downregulation targeted factors that are responsible for cell proliferation and RA progression. Several studies have indicated the antirheumatic effects and bone protective effects of these RNAs. Furthermore, the targeting of these therapeutic agents became easier with the introduction of nanoparticles, that could serve as a carrier for their effective delivery. Most recently, scientists have strategized methods to the next level involving codelivery of drug and siRNA/miRNA using a nanocarrier for achieving superior effects. The studies done for this combinatorial approach highlighted that the two therapeutic agents showed synergistic action and reduced inflammation, bone, and cartilage erosion, and ultimately slowed RA progression without causing any drug loss or adverse side effects. In this book chapter, we have discussed the combination therapy involving drug and gene (siRNA/miRNA) delivery, to effectively target the intended site using different nanocarriers. Additionally, several applications and challenges associated with their clinical use are also discussed citing examples.