A chlorogenic acid-conjugated nanomicelle attenuates disease severity in experimental arthritis.

Rheumatoid arthritis (RA) is a systemic immune disorder marked by synovitis, bone damage, and cartilage erosion, leading to increased socio-economic burdens and reduced quality of life. Despite its unknown cause, advancements in understanding its pathophysiology have facilitated novel therapeutic approaches. Current treatments, including disease-modifying anti-rheumatic drugs (DMARDs) and biologics, often result in low efficacy and unnecessary side effects. To address the limitations of these drugs, carrier-based drug delivery systems, such as nanomicelles, have emerged as a promising solution. In this study, nanomicelles were synthesised utilizing PLGA (poly(lactic-co-glycolic acid)) as a backbone; this backbone is conjugated with chlorogenic acid (CGA), which is known for suppressing inflammation, and incorporates methotrexate (MTX), a model drug that is established for RA treatment. The nanomicelles were extensively characterized in terms of size, charge, drug loading, and drug-release behaviour. The in vivo assessment of MTX-PLGA-b-CGA nanomicelles in a collagen-induced arthritis model demonstrated a remarkable reduction in joint swelling, cartilage erosion, and disease severity. Furthermore, histological findings confirmed cartilage integrity and reduced expression of key pro-inflammatory markers, including receptor activator of nuclear factor kappa beta ligand (RANKL) and tumor necrosis factor (TNF-α). The approach based on the MTX-PLGA-b-CGA nanomicelles presents a biocompatible and potentially effective therapeutic strategy for management of the severity and progression of RA, providing a hopeful alternative for RA treatment.

A bioactive and biodegradable vitamin C stearate-based injectable hydrogel alleviates experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory joint disorder affecting nearly 1% of the global population. In RA, synovial joints are infiltrated by inflammatory mediators and enzymes, leading to articular cartilage deterioration, joint damage, and bone erosion. Herein, the 9-aminoacridine-6-O-stearoyl-L-ascorbic acid hydrogel (9AA-SAA hydrogel) was formulated by the heat-cool method and further characterized for surface charge, surface morphology, rheology, and cytocompatibility. Furthermore, we evaluated the therapeutic efficacy of the 9AA-SAA hydrogel, an enzyme-responsive drug delivery system with on-and-off switching capabilities based on disease severity against collagen-induced experimental arthritis in Wistar rats. The anti-inflammatory action of the US FDA-approved drug 9-aminoacridine (9AA) was revealed which acted through nuclear receptor subfamily 4 group A member 1 (NR4A1), an anti-inflammatory orphan nuclear receptor that inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Furthermore, we have explored the role of ascorbic acid, an active moiety of 6-O-stearoyl-L-ascorbic acid (SAA), in promoting the production of collagen production through ten-eleven translocation-2 (TET2) upregulation. Targeting through NR4A1 and TET2 could be the probable mechanism for the treatment of experimental arthritis. The combination of 9AA and ascorbic acid demonstrated enhanced therapeutic efficacy in the 9AA-SAA hydrogel, significantly reducing the severity of experimental arthritis. This approach, in contrast to existing treatments with limited effectiveness, presents a promising and more effective strategy for RA treatment by mitigating inflammation in experimental arthritis.