人参皂苷Rd固体脂质纳米粒的体外释放和大鼠的在体吸收

目的研究人参皂苷Rd固体脂质纳米粒(Rd-SLN)的体外释药特性、在大鼠肠道的吸收和体内药物动力学行为。方法采用透析法测定Rd-SLN体外释药速率;通过大鼠在体分段肠回流实验,研究Rd-SLN的肠道吸收行为;建立血浆样品中人参皂苷Rd的HPLC分析方法,在大鼠灌胃给药后测定不同时间的血药浓度,观察Rd-SLN在体内的吸收和药动学特征。结果Rd-SLN具有缓释特征。在十二指肠和空肠段,Rd-SLN与人参皂苷Rd对照溶液的吸收率差异没有显著性;在回肠和结肠段,Rd-SLN与对照溶液的吸收率差异有显著性。Rd-SLN在回肠段的吸收率高于其它肠段。与对照组相比,Rd-SLN组的血药浓度水平维持时间更长,其Cmax、MRT、AUMC和AUC均明显增加。结论Rd-SLN具有一定的缓释作用,其在回肠的吸收优于其他肠段,并且能明显提高人参皂苷Rd的生物利用度。

Studies on drug release in vitro and absorption in rat in vivo of ginsenoside Rd solid lipid nanoparticles

Aim To investigate the release feature of ginsenoside Rd solid lipid nanoparticles (Rd-SLN) in vitro,and to clarify the difference in absorption of Rd-SLN from varied rat intestinal segments and pharmacokinetic properties in vivo. Methods Dialysis method was used to determine ginsenoside Rd release rate from nanoparticles in vitro. Perfusion method was used to study the intestinal absorption of Rd-SLN in rat. HPLC assay was established to determine the concentration of ginsenoside Rd in plasma. After intragastric administration,the concentrations of drug in rat blood at different time points were recorded to investigate the absorption and pharmacokinetics of Rd-SLN. Results The release of ginsenoside Rd from Rd-SLN was slowed down and presented the property of sustained release. There was no significant difference between the absorption rate of Rd-SLN and control solution in duodenum and jejunum. However,it was obviously different in ileum and colon. Comparing with other intestinal segments,significantly higher percentage of Rd-SLN was absorbed in colon. In Rd-SLN group,the concentration of ginsenoside Rd in blood was maintained,and the Cmax,MRT,AUMC,and AUC were all increased. Conclusions Rd-SLN possesses sustained-release effect. The colon is the preferable absorption site for Rd-SLN in intestinal tract. Rd-SLN can enhance the oral bioavailability of ginsenoside Rd.