三七皂苷长循环纳米粒的肠吸收及药动学研究

Intestinal Absorption and Pharmacokinetics Study of Long-circulating Nanoparticles Loaded with Panax Pseudoginseng Saponins

目的:研究三七皂苷(PNS)长循环纳米粒(PNS-LCN)的肠吸收及药动学。方法:采用大鼠外翻肠囊实验,测定PNS、PNS-LCN和PNS-壳聚糖物理混合物(Cs)中三七皂苷R1、Rg1、Rb1在大鼠十二指肠、空肠、回肠、结肠的渗透系数(Papp);大鼠分别灌胃给予PNS、PNS-LCN、PNS-Cs后于不同时间点取血,测定大鼠血浆中R1、Rg1、Rb1的血药浓度。结果:与PNS比较,PNS-LCN中R1在十二指肠和空肠,Rg1在空肠和回肠,Rb1在回肠和结肠的Papp升高;PNS-Cs中R1在十二指肠,Rg1在十二指肠、空肠和回肠,Rb1在十二指肠、空肠、回肠和结肠的Papp升高,差异有统计学意义(P<0.01或P<0.05)。PNS-LCN中R1、Rg1、Rb1生物利用度分别为PNS的3.65、3.63、2.96倍;PNS-Cs中R1、Rg1、Rb1生物利用度分别为PNS的0.31、0.77、1.36倍。结论:PNS-LCN可以明显提高PNS中R1、Rg1、Rb1的生物利用度,是PNS-LCN提高PNS渗透性和延长PNS在大鼠体内消除时间等综合作用的结果。

OBJECTIVE： To study the intestinal absorption and pharmacokinetics of long-circulating nanoparticles loaded with Panax pseudoginseng saponins （PNS-LCN）. METHODS： The osmotic coefficient （Papp） of notoginsenoside R1 （R1）, ginsenoside Rg1（Rg1） and ginsenoside Rbl（Rbl） from PNS, PNS-LCN and PNS-chitosan physical mixtures （PNS-Cs） in duodenum, jejunum, ileum and colon were determined in everted intestinal sac test. The blood samples of rats were collected at different time points after intragastrical administration of PNS, PNS-LCN and PNS-Cs, and plasma concentrations of Ra, Rg~ and Rb~ were detected. RE- SULTS ： Compared with PNS, Papp of R1 from PNS-LCN in duodenum and jejunum, Rg1 in jejunum and ileum, Rb1 in ileum and colon were increased; Papp of RI from PNS-Cs in duodenum, Rg1 in duodenum, jejunum and ileum, Rb1 in duodenum, jejunum, ileum and colon were increased; there was statistical significance（P〈0.01,P〈0.05）. The bioavailability of R1 Rg1 and Rb1 from PNS-LCN were 3.65, 3.63 and 2.96 folds of PNS; the bioavailability of R1, Rg1and Rb1 from PNS-Cs were 0.31, 0.77 and 1.36 folds of PNS, respectively. CONCLUSIONS： PNS-LCN can significantly increase bioavailability of R1, Rg1 and Rb,, PNS-LCN can improve the bioavailability of notoginsenoside R1, Rg1 and Rb~ significantly, which result from PNS-LCN improve the permea- bility of PNS and prolong the time of PNS clearance in rats.