Innovative Lipid Nanoparticles Co-Delivering Hydroxychloroquine and siRNA for Enhanced Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a debilitating autoimmune disorder characterized by chronic inflammation and joint damage. Despite advancements in treatment, complete remission remains elusive. In this study, we introduce a novel lipid nanoparticle formulation co-delivering hydroxychloroquine (HCQ) and siRNA targeting TNF-α (si) using microfluidic technology, marking the first use of such a combination for RA therapy. In LPS-stimulated RAW 264.7 cells, the nanoparticles effectively reduced inflammatory markers. When administered via an intra-articular injection in a rat model, they significantly decreased joint inflammation and demonstrated good biological safety. This pioneering approach highlights the potential of lipid nanoparticles as a dual-delivery platform for enhanced RA treatment through targeted intra-articular administration.