Preparation and evaluation of silymarin nanosuspensions for protective effects on stress-induced liver injury

OBJECTIVE To fabricate Silymarin(SM) nanosuspensions(NSs) and evaluate their protective effect on stress-induced liver injury. METHODS SM nanosuspensions were tailored by combination of the anti-solvent precipitation and high pressure homogenization(HPH); the formulations were optimized by central composite design. The pharmacokinetics and pharmacodynamics of SM-NSs were also performed.RESULTS In light of the quadratic mathematical equations derived from the Design of Expert Software,the optimal formulation of SM-NSs consisted of PVP 0.34% and F188 0.36%. The morphology of NSs was found to be spherical with a diameter of about 150 nm using transmission electron microscope(TEM)observation. The pharmacokinetics experiment demonstrated that oral administration of SM-NSs significantly increased its bioavailability compared to the coarse powder(Cmax: 9.03 ± 2.39 mg · L^(-1);AUMC_(0→∞):3757.35±227.19 mg·L^(-1)·h; AUC_(0→∞):171.84±26.61 mg·L^(-1)·h). In pharmacodynamics,it was found that restraint stress produced oxidative effects and increased serum AST and ALT levels in mice,both of which were significantly inhibited by SM and SM-NSs; in addition,administration of SM-NSs showed more effective prevention against acute liver injury than SM coarse suspensions(r^2=0.986,0.984,P<0.05). CONCLUSION The results suggest that fabricated SM-NSs exert potent hepatoprotective effects and attenuate restraint stress-induced liver injury. The study provides an effective approach to improving the property of SM,which can be used for treatment of liver diseases.