大蒜油固体脂质纳米粒大鼠体内药动学的研究

Pharmacokinetics of Solid Lipid Nanoparticles Containing Garlic Oil in Rats

目的研究大蒜油的血药浓度测定方法及其在大鼠体内的药动学。方法12只健康大鼠,单剂量(含大蒜油每只10mg)颈静脉注射给大蒜油固体脂质纳米粒和大蒜油注射液,在设计的时间点从颈静脉取血,采用气相电子捕获法同时测定大蒜油中指标性成分二烯丙基三硫化合物和二烯丙基二硫化合物在全血中药物浓度,药动学参数采用DAS2.0程序进行统计矩处理。结果大鼠颈静脉注射给药后,大蒜油的指标性成分DATS首先快速转化成DADS,然后继续降解;大蒜油固体脂质纳米粒中的DATS和DADS的MRT0-t分别为7.3和16.9min,ρmax分别为3574.3和21416.7μg.L-1;大蒜油注射液的DATS和DADS的MRT0-t分别为19.4和19.5,ρmax分别为3692.8和9335.8μg.L-1。tmax均为1min。结论本方法简单、快速,灵敏度和准确度较高,适合药动学研究。静注给药后大蒜油在大鼠体内表现为快速分布和消除,而大蒜油固体脂质纳米粒因被动靶向的关系消除比大蒜油注射液快。

OBJECTIVE To establish a GC-ECD method for simultaneously measuring the DATS and DADS levels in rat blood and to study the pharmacokinetics of solid lipid nanoparticles and injection containing garlic oil in rats. METHODS A single dose of GO-SLN and GO injection （containing 10 mg garlic oil） was administered to 12 healthy rats via the jugular vein. The concentrations of DATS and DADS in blood were simultaneously measured by GC-ECD. The pharmacokinetic parameters of solid lipid nanoparticle and injection containing garlic oil were calculated by program DAS2. 0. RESULTS DATS in garlic oil was first transformed into DADS and then degraded continuously after administration of two formulations via the jugular vein. The MRTs of DATS and DADS in GO-SLN were 7.3 and 16. 9 min while the ρmax were 3 574. 3 and 21 416. 7 μg·L^-1 ,respectively. Accordingly,the MRTs of DATS and DADS in GO injection were 19. 4 and 19.5 min while the ρmax, were 3 692. 8 and 9 335.8 μg·L^-1 , respectively. However, all tmax was 1 min, CONCLUSION The method is simple, rapid and sensitive, it is suitable for the pharmacokinetic research of GO in rat blood. The results showed that the distribution and elimination of DATS and DADS in garlic oil are rapid after injection in rats. Additionally,the elimination of GO-SLN is rapider than that of GO injection on account of targeting to liver.