Synthesis, characterization and <i>in vitro</i> evaluation of ticagrelor and its nano-formulation targeting the NLRP3 inflammasome pathway in synovial cells

This <i>in vitro</i> study explored the potential of ticagrelor (TCG) and its nano-formulation, TCG-β-CD/Lec (ticagrelor-loaded beta-cyclodextrin-lecithin nano-formulation), to modulate NLRP3 inflammasome activity using the SW982 synovial cell line as a rheumatoid arthritis experimental model. TCG was entrapped in β-CD/Lec NPs <i>via</i> solvent diffusion and characterized for size, polydispersity index (PDI), zeta potential, Fourier transform infrared (FTIR) spectroscopy, and UV-Vis spectrophotometry. The average sizes of blank and TCG-loaded nanoparticles were 87.73 nm and 143.1 nm, respectively, with low PDI values (0.36 and 0.32) and zeta potentials of -6.08 and -8.69 mV, indicating stable colloidal properties. FTIR confirmed successful drug encapsulation. The synthesized NPs showed an entrapment efficiency of 57.2% and a drug loading of 43.83%. Cellular assays were conducted to assess viability (MTT), oxidative stress (H₂DCFDA and SOD activity), and the inflammatory response in the treatment groups. Gene expression of NLRP3, ASC, CASP1, and NFκB was evaluated by qRT-PCR, and IL-1β secretion was measured <i>via</i> ELISA. Compared to free TCG, the nano-formulation exhibited reduced cytotoxicity. Both TCG and TCG-β-CD/Lec significantly reduced LPS and TNF-α-induced oxidative stress, evidenced by decreased ROS levels and enhanced SOD activity. In addition, both treatment groups suppressed IL-1β secretion and downregulated key genes involved in inflammasome activation. While the nano-formulation showed comparatively better outcomes, both treatment groups demonstrated potential antioxidant and anti-inflammatory effects. Overall, the findings suggest that TCG and the TCG-β-CD/Lec nano-formulation may help regulate inflammatory responses linked to NLRP3 inflammasome activation in rheumatoid arthritis, warranting further investigation for therapeutic development.