Nuclear Factor kappa B (NF-κB) Targeted Self-Assembled Nanoparticles Loaded with Methotrexate for Treatment of Rheumatoid Arthritis.

Abstract

BackgroundNanotechnology is one of the most productive approaches for specifically delivering drug payloads to the region of interest to decrease nonspecific distribution and unwanted toxicities.Material/MethodsWe prepared glycol chitosan stearate self-assembled nanoparticles loaded with methotrexate (MTX) for NF-κB targeting in treatment of rheumatoid arthritis (RA). The nanoparticles were prepared using hydrophobic modification of glycol chitosan (GC) with steric acid (SA) and was characterized using IR. The efficiency of nanoparticles after their physiochemical characterization was measured in vitro and by in vivo studies in mice.ResultsThe nanoparticles thus prepared were spherical in shape, 235 nm in diameter, and had negative zeta potential. The entrapment efficiency of MTX-GC-SA was more than 70%. The in vitro higher uptake of MTX-GC-SA in murine macrophage cells (RAW 264.7) was confirmed using confocal microscopy and FACS analysis. Systemic administration of MTX-GC-SA into collagen-induced arthritis (CIA) mice resulted in high accumulation in inflamed joints. The MTX-GS-SA revealed significantly better therapeutic efficacy against CIA mice compared to free MTX.ConclusionsThese findings highlight the potential of using this MTX-GC-SA nanoparticle formulation in suppressing inflammatory arthritis for effective treatment of RA.