不同粒径葛根素纳米乳动物体内吸收和分布研究

Absorption and Distribution of Puerarin Nanoemulsion with Different Particle Size

目的研究葛根素纳米乳(Pue NE)粒径因素对生物利用度、组织分布的影响。方法大鼠灌胃5种不同粒径的PueNE,采用HPLC测定血浆药物浓度,得出大鼠体内的药物血浆浓度-时间曲线,得出药动学参数。小鼠灌胃3种不同粒径的Pue NE,测定各组织不同时间的药物量,以药动学参数和靶向参数为靶向评价指标。结果由主要药动学参数可知,粒径为(10.3±1.7)﹑(24.8±2.3)﹑(38.7±3.0)﹑(54.6±6.0)、(98.4±9.8)nm的Pue NE,AUC的值分别为(16.79±3.67)、(20.20±4.23)、(30.16±5.78)、(36.77±3.98)、(32.69±4.04)μg.h.mL-1。与对照组比较,NE体系具有肺和肾靶向特性及滞留特性,AUC分别约提高5～6倍,MRT分别约延长2～3倍。结论在一定粒径范围内(10～60 nm),Pue NE的生物利用度(BA)与其粒径的大小成正比;其具有良好的肺、肾靶向性。

OBJECTIVE To study bioavailability of puerarin（Pue） in rats and learn the biodistribution of pue in mice, the different size range of puerarin （Pue） nanoemulsion（NE） were prepared. METHODS Rats were fed five different particle sizes Pue NE, mice were fed three different particle sizes Pue NE, respectively. The RP-HPLC method was established to determine the pue levels in the plasma and other tissues. The tissues distribution and targeting efficiency were evaluated by pharmacokinetic parameters （ AUC, MRT） and targeting parameters. RESULTS The pharmacokinetic parameters from the known, the particle size are （ 10. 3±1.7）, （24.8±2.3）, （38.7±3.0）, （54.6±6.0）, （98.4±9.8）nm, AUC values were （16.79±3.67）, （20.20±4.23）, （30. 16±5.78）, （36.77±3.98） , （32.69±4. 041 ）μg·h·mL^-1. In contrast to pue suspension group, NE showed a higher targeting effieiency in the Kidney and lung. The AUC of Pue in the liver and spleen were 5 - 6 times and the MRT were 2 - 3 times, re- speetively. CONCLUSION In a eertain size range （10 -60 nm）, the smaller the particle size, the smaller bioavailability. NE shows a higher targeting effieiency in the lung and kidney.