Drug Delivery Approaches for Rheumatoid Arthritis: Recent Advances and Clinical Translation Aspects

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease characterized with symmetrical progression of joint deformity that is often diagnosed at a chronic condition with other associated pathological conditions such as pericarditis, keratitis, pulmonary granuloma. Despite the understanding of RA pathophysiology in disease progression, current clinical treatment options such as disease-modifying anti-rheumatic drugs (DMARDs), biologics, steroids, and non-steroidal anti-inflammatory drugs (NSAIDs) provide only palliative therapy while causing adverse side effects such as off-target multi-organ toxicity and risk of infections. Further, available drug delivery strategies to treat RA pathogenicity does not successfully reach the site of action due to various barriers such as phagocytosis and first pass effect in addition to the disease complexity and unknown etiology, thereby leading to the development of irreversible joint dysfunction. Therefore, novel and effective strategies remain an unmet need to control the disease progression and to maintain the balance between pro- and anti-inflammatory cytokines. This review provides a comprehensive outlook on the RA pathophysiology and its corresponding disease progression. Contributions of synoviocytes such as macrophages, fibroblast-like cells in increasing invasiveness to exacerbate joint damage is also outlined in this review, which could be a potential future therapeutic target to complement the existing treatment regimens in controlling RA pathogenesis. Further, various smart drug delivery approaches under research to achieve maximum therapeutic efficacy with minimal adverse side effects have been discussed, which in turn emphasize the unmet challenges and future perspectives in addressing RA complications.