Phytosomal tripterine with selenium modification attenuates the cytotoxicity and restrains the inflammatory evolution via inhibiting NLRP3 inflammasome activation and pyroptosis

Inflammation mediates a variety of physiological and pathological events, prompting an importance of inflammation management for prevention and treatment of inflammatory diseases. This study formulated tripterine (Tri) into selenized phytosomes in an attempt to attenuate its cytotoxicity and potentiate its inflammation-regulating effect with selenium. Tri-loaded phytosomes (Tri-PTs) with selenium modification were prepared by a melting-hydration followed by in situ reduction technique. Then, selenized Tri-PTs (Se@Tri-PTs) were characterized by particle size, entrapment efficiency, and transmission electron microscope. The in vitro drug release and cellular uptake were performed to examine the formulation performance of Se@Tri-PTs. The cytotoxicity and anti-inflammatory efficacy through inhibiting NLRP3 inflammasome activation and pyroptosis were appreciated in murine J774A.1 macrophage cell line, respectively. The resultant Se@Tri-PTs presented a particle size of 125 nm around. Se@Tri-PTs exhibited attenuated cytotoxicity and improved cellular uptake in macrophages compared with free Tri or Tri-PTs. Also, Se@Tri-PTs inhibited the releases of caspase-1p20 and mature IL-1β, resulting in restriction of NLRP3 inflammasome activation that inhibits the formation of GSDMD-NT whereby to initiate pyroptosis. Altogether, our findings suggest that Se@Tri-PTs can inhibit inflammatory response by regulating the NLRP3/caspase-1 pathway, which in turn reduces pyroptosis via suppressing the cleavage of GSDMD.