透明质酸修饰的尿酸酶脂质体的制备及特性
CSTR:
作者:
作者单位:

重庆医科大学药物高校工程研究中心,重庆医科大学药物高校工程研究中心,重庆医科大学药物高校工程研究中心,重庆医科大学药物高校工程研究中心,重庆医科大学药物高校工程研究中心,重庆医科大学药物高校工程研究中心

作者简介:

通讯作者:

中图分类号:

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.


Preparation and characterization of hyaluronic acid-uricase liposomes
Author:
Affiliation:

Medicine Engineering Research Center,Key Laboratory of Biochemical&Molecular Pharmacology,Chongqing Medical University,Chongqing,400016,Medicine Engineering Research Center,Key Laboratory of Biochemical&Molecular Pharmacology,Chongqing Medical University,Chongqing,400016,Medicine Engineering Research Center,Key Laboratory of Biochemical&Molecular Pharmacology,Chongqing Medical University,Chongqing,400016,Medicine Engineering Research Center,Key Laboratory of Biochemical&Molecular Pharmacology,Chongqing Medical University,Chongqing,400016,Medicine Engineering Research Center,Key Laboratory of Biochemical&Molecular Pharmacology,Chongqing Medical University,Chongqing,400016,Medicine Engineering Research Center,Key Laboratory of Biochemical&Molecular Pharmacology,Chongqing Medical University,Chongqing,400016

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    目的 制备透明质酸修饰的尿酸酶脂质体(hyaluronic acid-uricase liposomes,UHLP),并对尿酸酶(uricase,UC)和UHLP的体外活性及稳定性进行研究。方法 采用逆向蒸发法制备UHLP,测定UHLP的包封率、粒径与zeta电位,用透射电镜对UHLP进行观察。考察游离UC和UHLP中UC的最适温度和最适pH,还考察了其热稳定性、贮存稳定性、酸碱稳定性、抗胰蛋白酶水解能力以及抗部分金属离子和有机化合物能力,并对UHLP提高UC活性的机制进行了初步研究。结果 UHLP的平均包封率为(57.27±3.93)%(n=3),平均粒径为(322.6±8.2)nm(n=3),zeta电位为(-19.4±1.7)mV(n=3)。透射电镜下UHLP呈分布均匀的圆形或椭圆形。游离UC和UHLP中UC最适温度均为40℃;游离UC最适pH为8.5,UHLP中UC最适pH为8.0。稳定性结果显示,UHLP中UC的热稳定性、贮存稳定性、酸碱稳定性、抗胰蛋白酶水解能力以及抗部分金属离子和有机化合物能力均优于游离UC。UHLP提高UC活性机制初步研究结果表明,UC经UHLP包裹后其活性发生改变,和UC与UHLP脂质膜的相互作用有关,它们在相互作用的过程中使UC的构象发生翻转,构效发生改变,UC活性中心暴露,从而导致其活性增强。结论 UHLP不仅能提高UC在体外的活性,还能提高UC在体外的稳定性。

    Abstract:

    Objective To prepare hyaluronic acid-uricase liposomes (UHLP) and to investigate the activity and stability of UHLP and uricase (UC) in vitro. Methods UHLP was prepared using reverse-phase evaporation and observed by transmission electron microscopy. The entrapment efficiency, particle size and zeta potential of UHLP were detected. The physical and chemical properties of UC in free UC and UHLP, including the optimum pH and temperature, thermal stability, storage stability, pH stability, stability to trypsinase, and stability to metal ions and organic compounds, were examined. In addition, the mechanism by which UHLP promotes UC activity was also explored. Results The mean entrapment efficiency of UHLP was (57.27±3.93)% (n=3), mean particle size was (322.6±8.2) nm (n=3), and mean zeta potential was (-19.4±1.7) mV (n=3). UHLP was round or oval in shape and was evenly distributed under transmission electron microscopy. The optimum temperature of UC in UHLP and free UC was 40℃, and the optimum pH values of UC in UHLP and free UC was 8.0 and 8.5, respectively. Thermal stability, storage stability, pH stability, stability to trypsin and stability to metal ions and organic compounds of UC in UHLP were better than those in free UC. The envelopment of UC with UHLP increased the activity of UC by reversing conformation and exposing active center of UC. Conclusion UHLP can not only enhance the activity but also improve the stability of UC in vitro.

    参考文献
    相似文献
    引证文献
相关视频

分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2015-09-05
  • 最后修改日期:2015-12-10
  • 录用日期:2016-01-21
  • 在线发布日期: 2016-09-26
  • 出版日期:
文章二维码
重要通知
友情提醒: 近日发现论文正式见刊或网络首发后,有人冒充我刊编辑部名义给作者发邮件,要求添加微信,此系诈骗行为!可致电编辑部核实:021-81870792。
            《海军军医大学学报》编辑部
关闭