Study on the Acute Toxicity and Antiarrhythmic Effects of Two Kinds of Long-Circulating Crebanine Nanoparticles
Objective To compare the acute toxicity and antiarrhythmic effect of the two kinds of long-circulating Crebanine(Cre)nanoparticles(PELGE-Cre-NPs,PLGA-Cre-NPs)prepared from two PEG-modified carrier materials(PELGE,PLGA),and to explore their synergistic and attenuated effects.Methods The acute toxicity test of PLGA-Cre-NPs and PELGE-Cre-NPs in mice were conducted by using Bliss method,and LD50 values were calculated by using of statistical software.The effect of PLGA-Cre-NPs and PELGE-Cre-NPs on ventricular fibrillation caused by trichloromethane in mice,ventricular arrhythmia caused by BaCl2 in rats and arrhythmia caused by aconitine in rats was observed.Results The LD50 of PLGA-Cre-NPs and PELGE-Cre-NPs after intravenous injection were 13.619 mg·kg-1 and 14.839 mg·kg-1,respectively,which showed an obvious increase in LD50 compared to that of Cre(LD50,9.382 mg·kg-1).Compared with the model control group,both nanoparticles significantly inhibited chloroform-induced ventricular fibrillation in mice and barium chloride-induced arrhythmia in rats,and significantly increased the threshold dose of aconitine induced ventricular premature beat(VPB),ventricular tachycardia(VT),ventricular fibrillation(VF)and cardiac arrest(CA)in rats(P＜0.05,P＜0.01,P＜0.001).Compared with Cre(5 mg·kg-1)group,the number of mice with high-dose of PELGE-Cre-NPs(5 mg·kg-1)restored sinus rhythm for≥5 minutes was significantly increased(P＜0.05).The threshold dose of aconitine in cardiac arrest was significantly increased(P＜0.05).Conclusion The toxicity of PLGA-Cre-NPs and PELGE-Cre-NPs were lower than that of Cre,and they had significant antiarrhythmic activity.Moreover,nanoparticles displayed stronger effect than Cre,and they can reduce toxicity of Cre.
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