吴茱萸碱脂质纳米粒的药代动力学和在体肠吸收特性研究

Pharmacokinetics and in situ intestinal absorption of evodiamine lipidic nanoparticle

研究吴茱萸碱脂质纳米粒在大鼠体内的药代动力学和在体肠吸收特性。采用溶剂蒸发法制备吴茱萸碱脂质纳米粒,并测量其粒径电位。雄性SD大鼠分别单剂量灌胃给予吴茱萸碱和吴茱萸碱脂质纳米粒后(按吴茱萸碱计,质量分数为250 mg/kg),在预设时间点取血并采用HPLC法测定血浆样品中吴茱萸碱的含量,用DAS 2.1.1软件分析药代动力学数据;建立大鼠在体单向肠灌流模型,研究吴茱萸碱脂质纳米粒在大鼠肠道内的吸收情况。结果显示,吴茱萸碱脂质纳米粒的平均粒径和电位分别为180.10 nm和−17.90 mV。吴茱萸碱和吴茱萸碱脂质纳米粒的药时曲线下面积分别为(862.60±14.03)和(4084.31±17.21)μg/L·h,峰浓度分别为(163.40±13.27)和(616.90±21.04)μg/L。吴茱萸碱脂质纳米粒在各个肠段的吸收均显著高于吴茱萸碱(P<0.05),且其在结肠的吸收优于其他肠段。其在胃、十二指肠、空肠、回肠和结肠的吸收速率常数分别为(45.10±6.08)×10^−5,(48.20±1.21)×10^−5、(22.10±3.18)×10^−5、(59.10±1.11)×10^−5和(90.00±3.85)×10^−5 s−1。其在十二指肠、空肠、回肠和结肠的有效渗透系数分别为(44.10±0.51)×10^−5、(17.21±0.77)×10^−5、(35.36±0.31)×10^−5和(40.33±0.34)×10^−5 cm/s。综上,吴茱萸碱脂质纳米粒增强了吴茱萸碱在大鼠肠道内的吸收,提高了吴茱萸碱在大鼠体内的口服生物利用度。

The aim of this study was to investigate the in vivo pharmacokinetic behavior characteristics and in situ intestinal absorption characteristics of the evodiamine lipidic nanoparticle in rats.Evodiamine lipidic nanoparticle was prepared by the solvent evaporation methods.The particle size and zeta potential of evodiamine lipidic nanoparticle were measured by dynamic light scattering analysis.Male SD rats were divided into two groups randomly.Each group was given single dose of evodiamine and evodiamine lipidic nanoparticle by gavage at evodiamine dose of 250 mg/kg,respectively.The blood samples were collected at scheduled time points.The content of evodiamine in plasma samples was determined by high performance liquid chromatography(HPLC)method.The main pharmacokinetic parameters of evodiamine and evodiamine lipidic nanoparticle were calculated using DAS 2.1.1 software.Moreover,the single-pass intestinal perfusion model was also established in rats to investigate the in situ intestinal absorption characteristics of evodiamine lipidic nanoparticle.The mean particle size and mean zeta potential of evodiamine lipidic nanoparticle were 180.10 nm and−17.90 mV,respectively.The area under the curve of evodiamine and evodiamine lipidic nanoparticle were(862.60±14.03)and(4084.31±17.21)μg/L·h,respectively,and the peak concentration were(163.40±13.27)and(616.90±21.04)μg/L,respectively.Moreover,the absorption of evodiamine lipidic nanoparticle was significantly higher than that of evodiamine in each segment of intestinal tract in rats(P<0.05).The absorption of evodiamine lipidic nanoparticle in colon was better than those of evodiamine lipidic nanoparticle in stomach,duodenum,jejunum and ileum.The absorption rate constant of evodiamine lipidic nanoparticle in stomach,duodenum,jejunum,ileum and colon were(45.10±6.08)×10^−5,(48.20±1.21)×10^−5,(22.10±3.18)×10^−5,(59.10±1.21)×10^−5 and(90.00±3.85)×10^−5 s−1,respectively,and the effective permeability coefficient in duodenum,jejunum,ileum and colon was(44.10±0.51)×10^−5,(17.21±0.77)×10^−5,(35.36±0.31)×10^−5 and(40.33±0.34)×10^−5 cm/s,respectively.All in all,evodiamine lipidic nanoparticle remarkably improved the in situ intestinal absorption of evodiamine in different segments of the intestinal tract in rats and its oral bioavailability in rats.