Gene Based Therapeutics and Targeted Nano Enabled Delivery Platforms for Management of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovial inflammation, progressive cartilage degradation, and bone erosion driven by complex cytokine networks and dysregulated immune cell activity. Although conventional therapies such as DMARDs, biologics, and JAK inhibitors have improved disease control, their efficacy remains variable and is often limited by systemic toxicity and incomplete suppression of pathogenic pathways. This review integrates gene based therapeutic strategies with nano enabled delivery platforms, highlighting how nanocarriers facilitate targeted and efficient modulation of key inflammatory pathways in rheumatoid arthritis. The particular emphasis is placed on molecular targets including pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), transcriptional regulators (NF-κB, STAT3), immune modulators (BAFF, IRF5), and regenerative mediators involved in cartilage and bone repair. The manuscript critically evaluates diverse delivery systems such as lipid-based nanoparticles, polymeric nanoparticles, dendrimers, inorganic and hybrid nanomaterials, RNA nanostructures, microneedles, injectable hydrogels, and scaffold based nano-reservoirs. The strategies for passive, active, and stimuli-responsive targeting of inflamed synovial tissue are discussed, highlighting their ability to enhance local therapeutic concentration while minimizing systemic exposure. Collectively, the integration of gene modulation with smart nanocarrier technologies represents a promising paradigm shift toward precision, site-specific, and disease-modifying interventions in rheumatoid arthritis.