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透明质酸修饰天冬酰胺酶自组装仿生纳米囊的稳定性及其体内药代动力学

刘煜莹, 李瑶, 杨强, 陈冉, 李开铃, 张景勍

刘煜莹, 李瑶, 杨强, 陈冉, 李开铃, 张景勍. 透明质酸修饰天冬酰胺酶自组装仿生纳米囊的稳定性及其体内药代动力学[J]. 中国药科大学学报, 2020, 51(4): 461-465. DOI: 10.11665/j.issn.1000-5048.20200411
引用本文: 刘煜莹, 李瑶, 杨强, 陈冉, 李开铃, 张景勍. 透明质酸修饰天冬酰胺酶自组装仿生纳米囊的稳定性及其体内药代动力学[J]. 中国药科大学学报, 2020, 51(4): 461-465. DOI: 10.11665/j.issn.1000-5048.20200411
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LIU Yuying, LI Yao, YANG Qiang, CHEN Ran, LI Kailing, ZHANG Jingqing. Stability and pharmacokinetics of hyaluronic acid-modified asparaginase self-assembled biomimetic nanocapsules[J]. Journal of China Pharmaceutical University, 2020, 51(4): 461-465. DOI: 10.11665/j.issn.1000-5048.20200411
Citation: LIU Yuying, LI Yao, YANG Qiang, CHEN Ran, LI Kailing, ZHANG Jingqing. Stability and pharmacokinetics of hyaluronic acid-modified asparaginase self-assembled biomimetic nanocapsules[J]. Journal of China Pharmaceutical University, 2020, 51(4): 461-465. DOI: 10.11665/j.issn.1000-5048.20200411
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透明质酸修饰天冬酰胺酶自组装仿生纳米囊的稳定性及其体内药代动力学

  • 1.

    重庆医科大学重庆药物高校工程研究中心，重庆 400016

  • 2.

    重庆市公共卫生医疗救治中心，重庆 400036

基金项目: 国家自然科学基金资助项目(No.30973645)；重庆市科委资助项目(No.CSTC2015jcyjBX0027)；重庆市教委资助项目(No.CYS19210)

Stability and pharmacokinetics of hyaluronic acid-modified asparaginase self-assembled biomimetic nanocapsules

  • 1.

    Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Chongqing 400016

  • 2.

    Chongqing Public Health Medical Center, Chongqing 400036, China

Funds: This study was supported by the National Natural Science Foundation of China (No.30973645), the Project Foundation of Chongqing Science and Technology Commission (No.CSTC2015jcyjBX0027) and the Project Foundation of Chongqing Municipal Education Committee (No.CYS19210)

摘要

    摘要
  • 摘要: 考察了透明质酸修饰的天冬酰胺酶(asparaginase, Asp)自组装仿生纳米囊（hyaluronic acid-modified asparaginase self-assembled bionic nanocapsules, ASNCs）的稳定性及药代动力学特性。使用分子自组装法制备ASNCs，考察其形态、粒径、Zeta电位和抗胰蛋白酶稳定性。大鼠静脉注射给予游离Asp和ASNCs后，取不同时间点下大鼠血浆样品测定Asp的活性。采用DAS药代动力学软件计算药代动力学参数。实验测定ASNCs的粒径为(99.17 ± 0.21) nm，电位为-(13.13 ± 0.60) mV。在胰蛋白酶溶液中，ASNCs表现出更优异的稳定性。ASNCs的活性-时间曲线下面积AUC0-48 h与天冬酰胺酶相比约提高了2倍，平均滞留时间MRT0-48 h约为Asp的1.7倍，生物利用度为Asp的195%。研究结果表明，透明质酸修饰的天冬酰胺酶自组装仿生纳米囊能提高天冬酰胺酶抗胰蛋白酶稳定性及生物利用度，延长了Asp在体内的循环时间。
    Abstract: The stability and pharmacokinetic properties of hyaluronic acid-modified asparaginase (Asp) self-assembled bionic nanocapsules (ASNCs) were preliminarily investigated. ASNCs were prepared by molecular self-assembly method to investigate their morphology, particle size, Zeta potential and antitrypsin stability. After intravenous injection of free Asp and ASNCs, rat plasma samples at different times were taken to determine Asp activity. Pharmacokinetic parameters were calculated by DAS pharmacokinetic software. The particle size of ASNCs was (99.17 ± 0.21) nm and the potential was -(13.13 ± 0.60) mV. In trypsin solution, ASNCs showed more excellent stability. The area under the activity-time curve (AUC0-48 h) of ASNCs was about 2 times higher than that of Asp; the mean residence time (MRT0-48 h) was about 1.7 times higher than that of Asp, and the bioavailability was 195% of Asp. The results showed that ASNCs could improve the stability and bioavailability of Asp against trypsin and prolong the circulation time of Asp in vivo.
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  • 收稿日期:  2020-03-13
  • 刊出日期:  2020-08-24

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