马钱子碱聚乳酸纳米粒在家兔体内的药动学研究

In vivo pharmacokinetics of brucine-loaded polylactide nanoparticles in rabbits

目的研究马钱子碱聚乳酸纳米粒(Bru-PLA-NPs)iv注射给药后在家兔体内的药动学行为。方法建立HPLC法测定家兔血浆中马钱子碱浓度。色谱柱为Kromasil C18(250mm×4.6mm,5μm);流动相为乙腈-水(23:77),水中含庚烷磺酸钠1.01g/L,磷酸二氢钾1.36g/L,加磷酸调节pH至2.8;体积流量为1mL/min;检测波长为265nm;柱温为25℃。采用3p87软件计算马钱子碱药动学参数。结果单剂量ivBru-PLA-NPs(4mg/kg)后马钱子碱在兔体内的药动力学数据符合三室模型,单剂量静注马钱子碱溶液(4mg/kg)后符合二室模型;与马钱子碱溶液相比,Bru-PLA-NPs给药后,马钱子碱的消除半衰期(t1/2β)提高6.6倍;生物利用度提高8.7倍。结论与马钱子碱溶液相比,Bru-PLA-NPsiv给药后马钱子碱在家兔体内的药动学行为发生了显著变化。

Objective To evaluate the pharmacokinetic behavior of brucine-loaded polylacticacid nano- particles （Bru-PLA-NPs） in rabbits. Methods An HPLC method was developed for determination of Bru in rabbit plasma. The separation of Bru was achieved with a Kromasil C18 column （250mm×4.6mm,5μm）. The mobile phase consists of acetonitrile and water （23 ： 77）. To each liter of water, 1.01 gram of sodium heptanesulfonate and 1.36 gram of potassium dihydrogen phosphate were added, and then the pH value of the water was adjusted to 2.8 with phosphoric acid. The flow rate was set at 1 mL/min; The detection wavelength was set at 265 nm; The column temperature was kept at 25 ℃. Compartmental pharmacokinetics was used for calculating the parameters using 3p87 software, a practical pharmacokinetic program by Chinese Association of Mathematic Pharmacology （Beijing, China）. Results The pharmacokinetic data of Bru obtained from the single dose iv administration of Bru-PLA-NPs and Bru solution fit threecompartment and two-compartment open models, respectively. Compared with Bru solution after a single dose iv administration, the elimination half-life （t1/2β） and bioavailability of Bru were increased by 6. 6 times and 8.7 times, respectively. Conclusion Compared with Bru solution, the pharmacokinetic behavior of Bru changes obviously, following the iv administration of Bru-PLA-NPs in rabbits.