载天冬酰胺酶磺丁基-β-环糊精脂质体的稳定性及相关机制  

Stabilities and related mechanism of sulfobutyl ether-β-cyclodextrin liposomes loaded with asparaginase

作　　者：李瑶 万胜利 张永红[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药物高校工程研究中心,重庆400016 [2]西南医科大学附属医院药学部,四川泸州400010

出　　处：《中国药理学通报》2017年第11期1596-1600,共5页Chinese Pharmacological Bulletin

基　　金：重庆市研究生科研创新项目(No CYS16133)

摘　　要：目的考察载天冬酰胺酶(asparaginase,Ase)磺丁基-β-环糊精脂质体(sulfobutyl ether-β-cyclodextrin liposomes loaded with asparaginase,ASDL)的稳定性,并探究其稳定性增强的相关机制。方法采用逆向蒸发法制备ASDL,通过酸碱稳定性、热稳定性、抗胰蛋白酶稳定性、血浆稳定性和贮存稳定性,考察ASDL的体外稳定性,并利用荧光光谱法探究其稳定性增强的相关机制。结果稳定性实验结果显示,ASDL的酸碱稳定性、热稳定性、抗胰蛋白酶稳定性、血浆稳定性和贮存稳定性都优于Ase。荧光实验结果显示,ASDL特性提高的原因可能与荧光发色团周围微环境和疏水结构的改变有关。结论磺丁基-β-环糊精脂质体能够有效保护Ase不受外界环境,如水解酶、p H、温度的影响,从而提高了Ase的稳定性。Aim To investigate the stabilities and related mechanism of sulfobutyl ether-β-cyclodextrin liposomes loaded with asparaginase( ASDL). Methods Reverse evaporating method was used for the preparation of ASDL,and the acid-base stability,thermal stability, antitrypsin stability, plasma stability and storage stability of ASDL were tested. Moreover,fluorescence spectrum method was utilized to explore the stability enhancement mechanisms of ASDL. Results The results of stability showed that the acid-base stability,thermal stability,antitrypsin stability,plasma stability and storage stability of ASDL were all superior to asparaginase. Fluorescence experiment results indicated that the improved characteristics of ASDL might be related to the changes of the surrounding microenvironment of fluorescent chromophore or the structure of hydrophobic. Conclusion ASDL can effectively protect asparaginase from the external environment,such as hydrolase,p H,temperature and so on,to improve the stabilities of asparaginase.

关 键 词：生物大分子 天冬酰胺酶 环糊精脂质体 稳定性 体外 荧光 

分 类 号：R345.69[医药卫生—基础医学] R943