天门冬酰胺酶纳米囊的药动学及生物等效性研究

Studies on pharmacokinetics and bioequiavailability of Asparaginase in Asparaginase nanocapsules

摘要:

作者研究了载天门冬酰胺酶（Asparaginase，AN）自组装透明质酸-聚乙二醇（Hyaluronic acid-graft-poly（ethylene glycol），HA-g-PEG）/γ-环糊精（γ-cyclodextrin，γ-CD）纳米囊（HA-g-PEG/γ-CD nanocapsules loaded with AN，AHRPs）在雄性SD大鼠体内的药代动力学和生物等效性。考察了AHRPs的透射电镜、粒径、Zeta电位、包封率，并分别测定大鼠静脉给予AHRPs和游离AN后，不同时间点大鼠血浆样品中AN的活性。采用DAS 2.1.1软件计算药动学参数，对AHRPs和游离AN进行生物等效性评价。经计算，AHRPs的平均粒径为（410.30±3.20） nm，Zeta电位为（-31.40±1.65） mV，平均包封率为（42.80±4.37）%。AHRPs和游离AN的主要药动学参数AUC（0~48 h）分别为（104.01±1.68） U/（mL·h）和（46.38±1.98） U/（mL·h），AUC（0~∞）分别为（131.03±19.67） U/（mL·h）和（51.44±3.01） U/（mL·h），t1/2分别为（4.31±1.53） h和（1.86±0.38） h。与游离AN比较，AHRPs的AUC（0~48 h）、AUC（0~∞）和t1/2分别提高了2.24、2.55和2.32倍。AUC（0~48 h）、AUC（0~∞）和Cmax的90%可置信区间分别为77.1%～78.7%、76.7%～78.3%、98.9%～100.5%。AHRPs延长了AN在大鼠体内的生物半衰期，提高了AN在大鼠体内的生物利用度，且AHRPs与游离AN不具有生物等效性。

Abstract:

To study the pharmacokinetic and bioequivalence of Arparaginase Hyaluronic acid-graft-poly(ethylene glycol) / γ-cyclodextrin nanocapsules (AHRPs) in SD rats. We observed the image of AHRPs under the transmission electron microscopy. The size, zeta potential, entrapment efficiency were detected. The activity of AN was assayed after respectively intravenous injecting AHRPs and free AN in rats. The pharmacokinetic parameters were calculated by software DAS 2.1.1, then the bioequivalence was judged. After calculating, the average particle size was (410.30±3.20) nm, zeta potential was (-31.40±1.65) mV, average entrapment efficiency was (42.80±4.37)%. AUC(0-48h) of AHRPs and free AN was (104.01 ±1.68) U/mL*h and (46.38 ±1.98) U/mL*h, AUC(0-∞) was (131.03 ±19.67) U/mL*h and (51.44 ±3.01) U/mL*h, t1/2 was (4.31±1.53) h and (1.86±0.38Z) h, respectively. Compared with free AN, the AUC(0-48h), AUC(0-∞) and t1/2 of AHRPs increased 2.24, 2.55 and 2.32 times, respectively. The 90% confidential intervals of AUC(0-48h), AUC(0-∞) and Cmax of tested formulation were 77.1%~78.7%，76.7%~78.3%，98.9%~100.5%, respectively. AHRPs can improve the bioavailability and extend the biological half-life of AN in rats. AHRPs and free AN are not bioequivalent.