Nanocarrier based drug delivery for rheumatoid arthritis: Current strategies and future directions

The application of nanotechnology in drug delivery systems has attracted considerable scientific interest, particularly with respect to improving the therapeutic efficacy and safety profiles of pharmacological agents. This review critically examines nanotechnology-based drug delivery systems for the management of rheumatoid arthritis (RA), a chronic systemic autoimmune disease characterized by persistent synovial inflammation, progressive joint destruction, and significant extraarticular sequelae. Conventional pharmacological strategies such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and biological disease-modifying anti-rheumatic drugs (bDMARDs) provide disease control but are associated with significant adverse effects upon prolonged use, inadequate joint specific drug concentrations, and limited responsiveness in a subset of patients. Nanotechnology offers a compelling therapeutic solution by enabling targeted drug delivery to inflamed synovial tissue, thereby enhancing bioavailability, reducing systemic toxicity, and extending drug half-life. This review discusses diverse nanotechnology platforms, such as liposomes, dendrimers, polymeric nanoparticles, hydrogels, metal, inorganic nanoparticles, nucleic acid-based carriers, and stimuli-responsive nanocarriers evaluated for RA treatment. The evidence underscores the potential of these systems to overcome the limitations of traditional therapies and to facilitate precision therapeutics in RA. The review also addresses existing challenges in nanomedicine translation, such as inter-patient variability, protein corona formation, endosomes (as a barrier), biocompatibility, and the need for rigorous clinical validation, while outlining future directions including exosome mediated delivery, biomimetic nano-carriers, and stimuli-responsive platforms.