Targeting NF-κB and JAK/STAT pathways in rheumatoid arthritis: emerging nanocarrier-based drug delivery approaches.

Rheumatoid arthritis (RA) is characterized by synovial inflammation, cartilage deterioration, and irreversible joint destruction, marking it as a chronic, progressive inflammatory disease. NF-κB and JAK/STAT are key molecular pathways that regulate inflammatory cytokine production, immune cell activation, and the persistence of inflammatory responses in RA. Conventional pharmacotherapies, including biologics and disease-modifying antirheumatic medications, are effective for treatment but face limitations like rapid clearance, systemic toxicity, poor absorption, and inadequate targeting of inflammatory areas. Recent advancements in nanocarrier-based drug delivery systems enhance tissue-specific targeting, improve pharmacokinetics, and enable controlled release, addressing existing limitations. This review demonstrates novel nanocarrier platforms aimed at modulating the NF-κB and JAK/STAT pathways, such as liposomes, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, and nanoemulsions. The effective encapsulation by these nanocarriers enhances the stability and therapeutic index of small-molecule inhibitors, nucleic acids (siRNA, miRNA), phytochemicals, and biologics. Stimuli-responsive systems aid controlled drug release triggered by oxidative stress, acidic pH, or enzymatic activity in RA joints, while surface-functionalized nanoparticles facilitate targeted delivery to inflamed synovium via ligand–receptor interactions. The combination of pathway-specific therapies and advanced nanocarrier technology holds promise for improving the care of RA by reducing systemic adverse effects, enhancing therapeutic precision, and improving patient outcomes. To enhance the effectiveness and commercial viability of RA treatments on these platforms, additional preclinical and clinical research is essential.