Formononetin-loaded solid lipid nanoparticles attenuate inflammatory signaling in TNF-α-stimulated MH7A synoviocytes

Rheumatoid arthritis (RA) is associated with persistent synovial inflammation induced by pro-inflammatory cytokines and matrix metalloproteinases. Formononetin (FN), a plant isoflavone, has anti-inflammatory and antioxidant properties with therapeutic potential for RA. This research aimed to prepare FN-loaded solid lipid nanoparticles (FN-SLNPs) and determine whether nanoencapsulation preserves chemical identity, increases antioxidant potential, and enhances anti-inflammatory activity in tumor necrosis factor-α (TNF-α)-stimulated MH7A synoviocytes. FN-SLNPs were characterized by particle size and zeta potential analysis, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), UV-visible spectroscopy, and antioxidant profiling, including total flavonoid content, total phenolic content, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. In vitro biological activity in TNF-α-stimulated MH7A cells was evaluated using cytotoxicity analysis by MTT assay, protein quantification by ELISA, and gene expression analysis by qRT-PCR. FN-SLNPs showed a hydrodynamic diameter of 148 ± 42 nm and a zeta potential of − 27.3 ± 1.3 mV. SEM revealed crystalline lipid domains. FTIR confirmed the chemical retention of isoflavone functional groups. Flavonoid content and total phenolic content increased with FN-SLNP loading compared with pure FN. DPPH radical scavenging activity was highest for FN-SLNPs at 20 mg compared with pure FN. TNF-α increased MH7A cell viability to 145.2 ± 5.8%. FN-SLNPs at 100 µg/mL reduced viability to 85.4 ± 3.1%, decreased interleukin-1β (IL-1β) protein levels from 0.0182 ± 0.0015 to 0.0035 ± 0.0003 µg/mL, and reduced IL1B gene expression from 18.50 ± 1.20 to 2.90 ± 0.25. These findings indicate that FN-SLNPs preserve the chemical identity of FN, enhance its antioxidant activity, and potentiate anti-inflammatory responses in MH7A synoviocytes.