姜黄素固体脂质纳米粒在大鼠体内的药动学

Oral pharmacokinetics of solid curcumin lipid nanoparticles in rats

目的:研究姜黄素固体脂质纳米粒在SD大鼠体内的口服药动学情况。方法:大鼠单剂量灌胃给予姜黄素固体脂质纳米粒和游离药姜黄素,眼底静脉丛取血,以醋酸乙酯处理血浆样品,尼群地平为内标,高效液相法(HPLC)测定血浆中姜黄素的含量,并用药物与统计(Drug and Statistics,DAS)软件分析处理药动学数据。结果:姜黄素固体脂质纳米粒和游离药姜黄素在大鼠体内的药动学行为均符合二室开放模型,姜黄素固体脂质纳米粒和游离药姜黄素的药动学参数分别如下:药时曲线下面积(AUC0-t)为(798.00±64.44)μg·h·L-1和(108.78±14.22)μg·h·L-1,药时曲线下总面积(AUC0-∞)为(939.49±114.18)μg·h·L-1和(126.99±28.14)μg·h·L-1,峰浓度(Cmax)为(93.84±5.66)μg·L-1和(72.46±2.66)μg·L-1,消除半衰期(t1/2)为(17.16±1.61)h和(4.71±1.18)h,姜黄素固体脂质纳米粒的AUC0-t、AUC0-∞、Cmax和t1/2分别提高了7.34,7.40,1.30和3.64倍。结论:姜黄素固体脂质纳米粒体内消除慢,血药浓度高,且明显提高了姜黄素的口服生物利用度。

OBJECTIVE To study the pharmacokinetics of solid curcumin lipid nanoparticles in SD rats.METHODS Rats were administrated with（i.g.）solid curcumin lipid nanoparticles and curcumin solution（50 mg·kg^-1）,respectively.Blood samples were collected from eye socket,and curcumin in blood plasma was extracted by ethyl acetate extraction and determined by HPLC using nitrendipine as the internal standard.Compartmental pharmacokinetics was analyzed by DAS software.RESULTS Mean plasma concentration-time curves of curcumin were both in accordance with open two-compartment mode after oral administration of curcumin solid lipid nanoparticles and curcumin solution in rats.After oral administration,AUC0-t,AUC0-∞,Cmaxand t1/2 of solid curcumin lipid nanoparticles were 7.34-fold,7.40-fold,1.30-fold and 3.64-fold higher than those of curcumin solution[（798.00±64.44）μg·h·L^-1 vs（108.78±14.22）μg·h·L^-1,（939.49±114.18）μg·h·L^-1 vs（126.99±28.14）μg·h·L^-1,（93.84±5.66）μg·L^-1 vs（72.46±2.66）μg·L^-1 and（17.16±1.61）h vs（4.71±1.18）h].CONCLUSION The solid curcumin lipid nanoparticles are eliminated slowly,with higher concentration in rat plasma.The bioavailability of curcumin increases remarkably compared with that of curcumin solution after oral administration.