| 摘要: |
| 目的 研究载天冬酰胺酶(Asp)自组装透明质酸-聚乙二醇(HA-g-PEG)/二甲基-β-环糊精(DCD)纳米囊(AHDPs)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AHDPs的透射电镜、粒径、zeta电位、包封率,并分别测定大鼠静脉给予AHDPs和游离Asp后,不同时间点大鼠血浆样品中Asp的活性。采用DAS 2.1.1软件计算药动学参数,对AHDPs和游离Asp进行生物等效性评价。结果 AHDPs的平均粒径为(439.63±8.49) nm,zeta电位为(-20.43±2.20) mV,平均包封率为(55.75±4.11)%(n=3)。AHDPs和游离Asp的主要药动学参数AUC0-48 h分别为(138.93±0.89) U·mL-1·h和(46.38±1.98) U·mL-1·h,AUC0-∞分别为(175.22±13.59) U·mL-1·h和(51.44±3.01) U·mL-1·h, t1/2分别为(4.46±1.04) h和(1.86±0.38) h。与游离Asp比较,AHDPs的AUC0-48 h、AUC0-∞和t1/2分别提高至约游离ASP的3.00、3.40和2.40倍。AUC0-48 h、AUC0-∞和Cmax的90%置信区间分别为76.9%~78.3%、76.9%~78.3%、92.8%~94.4%。结论 AHDPs延长了Asp在大鼠体内的生物半衰期,提高了Asp在大鼠体内的生物利用度,且AHDPs与游离Asp不具有生物等效性。 |
| 关键词: 天冬酰胺酶 纳米囊 药代动力学 生物等效性 |
| DOI：10.16781/j.0258-879x.2016.06.0690 |
| 投稿时间：2015-06-09修订日期：2015-09-17 |
| 基金项目: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. |
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| Pharmacokinetics and bioequivalence of self-assembly nanocapsules loaded with asparaginase |
| XIE Jiang-chuan,HU Xue-yuan,YAN Zi-jun,ZHOU Yun-li,ZHANG Jing-qing |
(Medicine Engineering Research Center, Chongqing Medical University, Chongqing 400016, China
*Corresponding author) |
| Abstract: |
| Objective To study the pharmacokinetics and bioequivalence of asparaginase (Asp) hyaluronic acid-graft-poly (ethylene glycol)/dimethyl-β-cyclodextrin (DCD) nanocapsules (AHDPs) in male Sprague-Dawley (SD) rats. Methods AHDPs were observed under the transmission electron microscope. The size, zeta potential and entrapment efficiency of AHDPs were examined. Asp activities were assayed after intravenous injection of AHDPs or free Asp in rats. Pharmacokinetic parameters were calculated by software DAS 2.1.1. Then the bioequivalence of AHDPs and free Asp were evaluated. Results The average particle size of AHDPs was (439.63±8.49) nm, zeta potential was (-20.43±2.20) mV, and entrapment efficiency was (55.75±4.11)% (n=3). AUC(0-48 h) of AHDPs and free Asp were (138.93±0.89) U·mL-1·h and (46.38±1.98) U·mL-1·h, the AUC0-∞ were (175.22±13.59) U·mL-1·h and (51.44±3.01) U·mL-1·h, and t1/2 was (4.46±1.04) h and (1.86±0.38) h, respectively. Compared with free Asp, the AUC0-48 h, AUC0-∞ and t1/2 of AHDPs were increased by 3.00, 3.40 and 2.40 times, respectively. The 90% confidential intervals of AUC0-48 h, AUC0-∞ and Cmax were 76.9%-78.3%, 76.9%-78.3% and 92.8%-94.4%, respectively. Conclusion AHDPs can prolong the biological half-life and improve the bioavailability of Asp in rats. AHDPs and free Asp are not bioequivalent. |
| Key words: asparaginase nanocapsules pharmacokinetics bioequivalence |
