Liu Zhidong, Zhang Qian, Ding Lingling, Li Chunhua, Yin Zhongpeng, Yan Guoqiang, Pi Jiaxin, Li Jiawei, Li Nan, Qi Dongli
Tianjin State Key Laboratory of Modern Chinese Medicine, No. 88 Yuquan Road, Nankai District, Tianjin 300193, P.R. China.
Curr Drug Deliv. 2016;13(4):600-10. doi: 10.2174/1567201812666150608095517.
Due to the effects of gastric acid, glycosidase and intestinal flora in the gastrointestinal environment, panax notoginseng saponins (PNS) can easily be resolved and metabolized when it is administered orally, limiting its oral bioavailability.
The formula of PNS nanoemulsion (PNS-N) was optimized using a pseudoternary phase diagram, and the PNS-N was prepared by high pressure homogenization. The type, particle size, polydispersity index (PDI), refractive index, pH and content of PNS-N were characterized. In vitro characteristics were investigated by drug release and physical stability. The pharmacokinetic properties of PNS-N were studied with rat intestine and SD rats. The optimized nanoemulsion formulation was Labrafil M 1944CS (58%), SP/EtOH (Km=1) (25%), solution of PNS (400mg/ml) (17%).
The results showed that the average particle size was (28.17±0.39) nm with PDI of 0.116±0.032, refractive index of 1.4491±0.0009 and pH of 4.58±0.03. In addition, the contents of R1, Rg1 and Rb1 were (4.64±0.21) mg/mL, (19.16±0.27) mg/mL and (11.77±0.08) mg/mL, respectively. The optimized PNS-N formulation exhibited a sustained drug release with good stability. PNS-N is still clear and transparent, without layering and precipitation after six months. In the study of absorption kinetics of PNS-N in rat intestine, the Papp of three main components of PNS-N increased 5 times than PNS solution (PNS-SOL) in rat intestine. And pharmacokinetic study in SD rats suggested a 2.58-fold increase of oral bioavailability compared with PNS-SOL.
The PNS-N has increased the absolute availability of PNS obviously and nanoemulsion is a potential formulation to improve oral bioavailability for PNS.
由于胃肠道环境中胃酸、糖苷酶及肠道菌群的作用，三七总皂苷（PNS）口服给药时易被分解代谢，限制了其口服生物利用度。
采用伪三元相图优化PNS纳米乳（PNS-N）的处方，并通过高压均质法制备PNS-N。对PNS-N的类型、粒径、多分散指数（PDI）、折光率、pH值及含量进行表征。通过药物释放和物理稳定性研究其体外特性。用大鼠肠段和SD大鼠研究PNS-N的药代动力学性质。优化后的纳米乳处方为Labrafil M 1944CS（58%）、SP/乙醇（Km = 1）（25%）、PNS溶液（400mg/ml）（17%）。
结果表明，平均粒径为（28.17±0.39）nm，PDI为0.116±0.032，折光率为1.4491±0.0009，pH值为4.58±0.03。此外，R1、Rg1和Rb1的含量分别为（4.64±0.21）mg/mL、（19.16±0.27）mg/mL和（11.77±0.08）mg/mL。优化后的PNS-N制剂呈现出药物缓释且稳定性良好的特点。PNS-N在6个月后仍清澈透明，无分层和沉淀现象。在大鼠肠段对PNS-N的吸收动力学研究中发现，PNS-N的三个主要成分在大鼠肠段的表观渗透系数（Papp）比PNS溶液（PNS-SOL）增加了5倍。在SD大鼠中的药代动力学研究表明，与PNS-SOL相比，口服生物利用度提高了2.58倍。
PNS-N显著提高了PNS的绝对生物利用度，纳米乳是提高PNS口服生物利用度的一种有潜力的剂型。
