丁香苦苷固体脂质纳米粒的药物动力学研究

Study on the pharmacokinetics of syringopicroside solid lipid nanoparticles

目的:采用血药浓度法对丁香苦苷固体脂质纳米粒(S-SLN)进行药物动力学研究,以阐明其体内行为。方法:将大鼠随机分为丁香苦苷(SYR)的0.9%氯化钠注射液低、中、高剂量组(10、20、40mg/kg)及S-SLN注射液组(10mg/kg),每组6只,分别对其进行尾静脉注射给药,在规定时间点采集大鼠血浆进行HPLC分析并计算药动学参数,并对以上4组的药动学参数进行比较。结果:SYR的0.9%氯化钠注射液低剂量组的T1/2(α)为5.65min,T1/2(β)为25.05min,AUC为258.48(μg/mL)·min,血浆清除率(CL)为0.04kg/min。S-SLN注射液组T1/2(α)和T1/2(β)为6.66、50.89min,AUC为764.73(μg/mL)·min,CL为0.01kg/min。S-SLN较低剂量SYR原型药物的半衰期延长,血药浓度增加,清除率降低。结论:将SYR制备成固体脂质纳米粒后延长了药物在循环系统中的滞留时间,并具有一定的缓释效果。

Objective:The pharmacokinetics of syringopicroside solid lipid nanoparticles(S-SLN)was studied by blood concentration method to elucidate its behavior in vivo.Methods:Rats were randomly divided into syringopicroside(SYR)saline injection low,medium and high dose groups(10,20,40 mg/kg)and S-SLN group(10 mg/kg),6 rats in each group.The rats were injected into tail vein respectively.The plasma of the rats was collected at the specified time and analyzed by HPLC.The pharmacokinetic parameters of plasma in 4 groups were calculated and compared.Results:The T1/2(α),T1/2(β),AUC and clearande rate(CL)of SYR saline injection low dose group were 5.65 min,25.05 min,258.48(μg/m L)·min and 0.04 kg/min,respectively.S-SLN T1/2(α)and T1/2(β)were 6.66 min and 50.89 min,ACU was 764.73(μg/m L)·min,and the CL was 0.01 kg/min.The halflife of S-SLN was longer than that of the same dosage of SYR,the concentration of S-SLN in blood increased,and the clearance rate decreased.Conclusion:The preparation of SYR solid lipid nanoparticles can prolong the retention time of the drug in the circulatory system,and has a certain sustained-release effect.