载天门冬酰胺酶自组装透明质酸-聚乙二醇/γ-环糊精纳米囊的体外活性和稳定性探究  

Study on in vitro activity and stability of asparaginase loaded in self-assembly of polyethylene glycol-hyaluronic acid/γ-cyclodextrin nanocapsules

作　　者：李瑶[1] 晏子俊[1] 李万玉[1] 胡雪原[1] 何丹[1] 张景勍[1] 

机构地区：[1]重庆医科大学药物高校工程研究中心,重庆400016

出　　处：《重庆医科大学学报》2016年第5期456-460,共5页Journal of Chongqing Medical University

基　　金：国家自然科学基金资助项目(编号:30973645);重庆市教委资助项目(高校优秀人才资助项目)

摘　　要：目的:制备载天门冬酰胺酶(asparaginase,AN)自组装透明质酸-聚乙二醇(hyaluronic acid-graft-poly(ethylene glycol),HA-g-PEG)/γ-环糊精(γ-cyclodextrin,γ-CD)纳米囊(HA-g-PEG/γ-CD nanocapsules loaded with AN,AHRPs),并对AHRPs及游离AN在体外的活性及稳定性进行研究。方法:采用自组装法制备了AHRPs,考察了AHRPs的透射电镜、粒径、Zeta电位、最适温度和最适p H,并通过贮存稳定性、抗胰蛋白酶水解能力、抗部分金属离子及有机化合物、热稳定性、酸碱稳定性和血浆稳定性等实验,对游离AN与AHRPs体外稳定性差异进行了一定的考察。结果:AHRPs的粒径为(410.30±3.20)nm,Zeta电位为(-31.40±1.65)m V,AHRPs和游离AN的最适温度分别为50℃和60℃,最适p H值均为7.5。稳定性实验结果显示,相同条件下,AHRPs的贮存稳定性、抗胰蛋白酶水解能力、抗金属离子和有机化合物、热稳定性、酸碱稳定性和血浆稳定性均优于游离AN。结论:AHRPs能同时提高游离AN在体外的活性及稳定性。Objective：To prepare asparaginase（AN）loaded in self-assembly of polyethylene glycol-hyaluronic acid/γ-cyclodextrin nanocopsules（AHRPs）,and then to investigate the in vitro activity and stability difference between AHRPs and free AN. Methods：AHRPs was prepared by self-assembly method. The image of AHRPs under the transmission electron microscopy was observed. The size,zeta potential,optimal temperature and optimal p H value were detected. The in vitro activity and stability of AHRPs and free AN were investigated by measuring storage stability,trypsin stability,the effect of several metal ions and organic compounds,thermal stability,acid- and basic-stabilities and plasma stability on free AN and AHRPs. Results：After calculating,the particle size was（410.30±3.20）nm,zeta potential was（-31.40±1.65）m V. The optimum temperature of AHRPs and free AN was 50 ℃ and 60 ℃,respectively. The optimum p H of AHRPs and free AN was 7.5. The results of stability experiments showed that,storage stability,trypsin stability,the effect of several metal ions and organic compounds,thermal stability,acid- and basic-stabilities and plasma stability of AHRPs all were better than those of free AN. Conclusion：AHRPs can improve the activity and significantly enhance the stability of AN in vitro.

关 键 词：天门冬酰胺酶 空心纳米囊 稳定性 最适p H 最适温度 

分 类 号：R945[医药卫生—微生物与生化药学]