天门冬酰胺酶聚乙二醇-透明质酸/磺丁基-β-环糊精纳米粒体外稳定性的初步研究

Preliminary study on the stability of asparaginase loaded in self-assembly of polyethylene glycol-hyaluronic acid / sulfobutyl ether-β-cyclodextrin nanoparticles

目的制备含载天门冬酰胺酶(Asp)的自组装聚乙二醇-透明质酸/磺丁基-β-环糊精纳米粒(THSCD),并初步研究两者在体外的活性以及稳定性。方法采用自组装法制备THSCD;分别从最适温度、最适p H、酸碱稳定性、热稳定性、贮存稳定性、血浆稳定性、抗胰蛋白酶水解能力、部分金属离子及有机化合物影响来考察THSCD中Asp和游离Asp的差异。结果THSCD的最适温度为50℃,游离Asp最适温度为60℃。THSCD的最适p H为6.5,游离Asp的最适p H为7.5。THSCD的热稳定性、贮存稳定性、酸碱稳定性、血浆稳定性测定、抗胰蛋白酶水解能力和抗部分金属离子和有机化合物能力均比游离Asp好。结论 THSCD在提高了Asp在体外活性的同时,也明显地增强了游离Asp在体外的稳定性。

OBJECTIVE To prepare asparaginase（ Asp） loaded in self- assembly of polyethylene glycol- hyaluronic acid / sulfobutyl ether- β- cyclodextrin nanoparticles（ THSCD）,and to investigate the in vitro activity and stability differences between THSCD and free Asp. METHODS THSCD was prepared by self- assembly method. To investigate the differences,the optimum temperature,optimum p H,acid and basic stabilities,thermal stability,storage stability,plasma stability,trypsin stability and effect of several metal ions and organic compounds on free Asp and THSCD were tested,by measuring the Asp activity. RESULTS The optimum temperature of THSCD was 50 ℃,The optimum temperature of free Asp was 60 ℃. The optimum p H of THSCD was 6. 5 and free Asp was 7. 5. Thermal stability,storage stability,acid- and basic- stabilities,proteolytic stabilities,trypsin stability and effect of several metal ions and organic compounds of THSCD were all better than free Asp. CONCLUSION THSCD can improve the activity and significantly enhances the stability of free Asp in vitro.