Nanomedicine Approaches for Rheumatoid Arthritis (RA): Targeted Therapy and Controlled Drug Release

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder characterized by persistent synovial inflammation, progressive cartilage degradation, bone erosion, and joint deformity, ultimately leading to functional disability and reduced quality of life. Despite significant advances in disease management, conventional therapeutic approaches, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional disease-modifying antirheumatic drugs (DMARDs), biologic agents, and Janus kinase (JAK) inhibitors, are frequently associated with limited tissue specificity, poor pharmacokinetic profiles, systemic adverse effects, and variable patient responses. These limitations have driven the development of nanomedicine-based drug delivery systems that offer enhanced targeting capabilities, improved drug stability, prolonged circulation time, and controlled drug release at inflamed joints. This review comprehensively summarizes recent advances in nanomedicine approaches for rheumatoid arthritis, with particular emphasis on targeted therapy and controlled drug release strategies. The review discusses the design principles and therapeutic potential of various nanocarriers, including liposomes, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, nanostructured lipid carriers, polymeric micelles, metallic nanoparticles, mesoporous silica nanoparticles, hydrogels, and extracellular vesicle-based systems. It further explores passive and active targeting mechanisms, stimuli-responsive drug release platforms, and nanocarrier-mediated delivery of anti-inflammatory agents, biologics, nucleic acids, and emerging therapeutics. Recent preclinical and clinical developments demonstrating improved therapeutic efficacy, reduced systemic toxicity, enhanced bioavailability, and modulation of inflammatory pathways are critically evaluated. Furthermore, the review highlights current challenges related to biological barriers, long-term biosafety, large-scale manufacturing, regulatory approval, and clinical translation while discussing emerging trends such as biomimetic nanocarriers, artificial intelligence-assisted nanomedicine design, precision medicine, and multifunctional theranostic platforms. Overall, advanced nanomedicine represents a promising strategy for improving the safety, efficacy, and personalization of rheumatoid arthritis treatment and holds significant potential for transforming future clinical management of this debilitating autoimmune disease. Keywords: Rheumatoid arthritis; Nanomedicine; Targeted drug delivery; Controlled drug release; Nanocarriers.