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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.
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 of that oral administration of SM-NSs significantly increased its bioavailability compared to the coarse powder (Cmax: 9.03 ± 2.39 mg · A ~ (-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 inhibited 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. which study provides an effective approach to improving the property of SM, which can be used for treatment of liver diseases.