天门冬酰胺酶自组装空心纳米囊的药代动力学及生物等效性  

Pharmacokinetics and bioequivalence assessment of a self-assembled asparaginase nanocapsule in rats

作　　者：晏子俊[1] 谢江川[1] 何丹[1] 胡雪原[1] 张景勍[1] 

机构地区：[1]重庆医科大学药学院重庆高校药物工程研究中心,重庆400016

出　　处：《南方医科大学学报》2016年第1期90-93,共4页Journal of Southern Medical University

基　　金：国家自然科学基金(30973645);重庆市首批高等学校优秀人才资助计划~~

摘　　要：目的研究载带天门冬酰胺酶（AN）的自组装透明质酸-聚乙二醇（HA-g-PEG）/磺丁基-β-环糊精（S-CD）纳米囊（AHSPs）在雄性SD大鼠体内的药代动力学和生物等效性。方法考察了AHSPs的透射电镜、粒径和Zeta电位,并分别测定大鼠静脉给予AHSPs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AHSPs和游离AN进行生物等效性评价。结果经计算,AHSPs的平均粒径为413.80±10.97 nm,Zeta电位为-20.37±2.38 m V。AHSPs和游离AN的主要药动学参数AUC_（0~48 h）分别为137.34±1.82 U/m L和46.38±1.98 U/m L,AUC_（0~∞）分别为164.66±6.88 U/m L和51.44±3.01 U/m L,t1/2分别为4.62±0.60 h和1.86±0.38 h。与游离AN比较,AHSPs的AUC_（0~48 h）、AUC_（0~∞）和t1/2分别提高了2.96、3.20和2.48倍。AUC_（0~48 h）、AUC（0~∞）和Cmax的90%可置信区间分别为75.0%~76.5%、74.3%~76.1%、95.1%~96.7%。结论 AHSPs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AHSPs与游离AN不具有生物等效性。Objective： To study the pharmacokinetics and bioequivalence of asparaginase loaded in hyaluronic acid- graft- poly（ethylene glycol）/ sulfobutylether- β- cyclodextrin nanocapsules（AHSP） in SD rats. Methods The morphology of AHSP was observed under the transmission electron microscope and the particle size and zeta potential were measured. AHSP and free asparaginase were intravenously injected in rats, and the plasma asparaginase activity was measured at different time points after the injections. The pharmacokinetic parameters were calculated using the software DAS 2.1.1 to assess the bioequivalence of AHSP and free asparaginase. Results AHSP had an average particle size of 413.80±10.97 nm with a zeta potential of-20.37±2.38 m V. The AUC（0- 48 h）of AHSP and free asparaginase was 137.34 ± 1.82 U/m L and 46.38 ± 1.98 U/m L, and their AUC（0- ∞）was164.66±6.88 U/m L and 51.44±3.01 U/m L with half-lives of 4.62±0.60 h and 1.86±0.38 h, respectively. Compared with free AN,AHSP exhibited increased AUC（0- 48 h）, AUC（0- ∞）, and half- life by 2.24, 2.55 and 2.32 folds, respectively. The 90% confidential intervals of AUC（0- 48 h）, AUC（0- ∞）and Cmaxof the tested formulation were 75.0%- 76.5%, 74.3%- 76.1%, and 95.1%- 96.7%,respectively. Conclusion AHSP can improve the bioavailability and extend the biological half-life of asparaginase in rats, and AHSP and free asparaginase are not bioequivalent.

关 键 词：门冬酰胺酶 纳米囊 药代动力学 生物等效性 

分 类 号：R969.1[医药卫生—药理学]