Revolutionizing rheumatoid arthritis therapy: the potential of lipid nanocarriers

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovitis, systemic inflammation and autoantibodies, leading to joint damage and disability. RA pathogenesis is characterized by a dysregulated interaction between immune cells, particularly B cells and T cells, which release inflammatory cytokines. This review explores the pivotal role of these immune cells in sustaining the inflammatory response and contributing to tissue injury. We provide a comprehensive overview of current RA therapies, highlighting the limitations of conventional treatments and the pressing need for targeted drug delivery systems such as lipid nanocarrier-based therapies, including nano-emulsions, solid lipid nanoparticles (SLNs), niosomes, liposomes, transferosomes, and ethosomes. Emphasizing niosomes, we discuss their capacity to encapsulate multiple drugs, significantly enhancing bioavailability and therapeutic efficacy. By directing drug-loaded niosomes to inflamed synovial sites, this innovative approach minimizes systemic side effects while maximizing localized drug concentrations, thereby optimizing treatment outcomes for RA patients. This review underscores the importance of targeted (nano)drug delivery in improving patient's life quality and represents a significant step toward more effective, personalized RA therapies by deepening our understanding of the underlying mechanisms.

Fig. 1. Structure of healthy and rheumatoid arthritis (RA) inflamed joint.

Fig. 2. Structure of the different mentioned lipid nanostructures. (a) Nano-emulsions, (b) solid lipid nanoparticles (SLNs), (c) niosomes, (d) liposomes, (e) transferosomes, and (f) ethosomes.

Fig. 3. Mechanism of how liposomes and SLNs can suppress the RA disease. The autoantibodies form immune complexes that deposit in the synovial joints, triggering activation of the complement cascade and resident immune cells. The activation of antigen presenting cells (APCs) can activate CD4⁺ T cells (especially the Th1 and Th17 subsets) and B cells to infiltrate the synovium. As the disease progresses, macrophages and fibroblast-like synoviocytes (FLS) get activated and produce high levels of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-17, perpetuating a state of chronic synovial inflammation. NPs once administered systemically they can target inflamed joints, with a lower drug dose they can reduce the inflammation of the joints by reducing TNF-α, pannus formation and bone destruction.

Fig. 4. Mechanism of how transfersome, noisome and ethosome can suppress RA. Once topically administered, the NPs enhance skin retention and reduces the inflammation in the joint.