【摘要】：目的制備載天冬酰胺酶(asparaginase,AN)透明質(zhì)酸-聚乙二醇[hyaluronic acid-graft-poly(ethylene glycol),HA-g-PEG]/α-環(huán)糊精(α-cyclodextrin,α-CD)納米囊(HA-g-PEG/α-CD hollow nanocapsules loaded with asparaginase,AHAPs),并對其體外活性及穩(wěn)定性進行初步考察。方法采用自組裝法制備AHAPs,測定AHAPs的最適溫度、最適pH、粒徑、zeta電位和包封率,并通過熱穩(wěn)定性、酸堿穩(wěn)定性、抗胰蛋白酶水解能力、抗金屬離子和有機化合物能力、血漿穩(wěn)定性和貯存穩(wěn)定性實驗對游離AN與AHAPs的體外穩(wěn)定性差異進行考察。通過熒光實驗對AN與空白HA-g-PEG/α-CD納米囊的相互作用進行研究。結(jié)果 AHAPs的最適溫度為50℃,最適pH值為7.0,測得平均粒徑為(424.53±7.25)nm,zeta電位為(-48.77±0.99)mV。經(jīng)計算,AHAPs的平均包封率為(64.40±1.82)%。穩(wěn)定性實驗結(jié)果顯示,AHAPs中AN的體外穩(wěn)定性及活性明顯優(yōu)于游離AN,且部分實驗結(jié)果差異具有統(tǒng)計學(xué)意義(P0.05)。熒光實驗結(jié)果表明,AHAPs中AN生物活性的提高可能與AN和空白HA-g-PEG/α-CD納米囊的相互作用引起蛋白質(zhì)殘基微環(huán)境和酶構(gòu)象改變相關(guān)。結(jié)論 AHAPs不僅提高了AN的活性,而且明顯增強了AN的體外穩(wěn)定性。
[Abstract]:Objective to prepare HA-g-PEG/ 偽 -CD hollow nanocapsules loaded with asparaginase, containing asparaginase,AN hyaluronic acid-polyethylene glycol [hyaluronic acid-graft-poly (ethylene glycol), HA-g-PEG] / 偽 -cyclodextrin (偽 -cyclodextrin) The activity and stability of AHAPs), in vitro were also investigated. Methods AHAPs, was used to determine the optimum temperature, particle size, zeta potential and entrapment efficiency of AHAPs, and the thermal stability, acid-base stability, anti-trypsin hydrolysis ability, anti-metal ions and organic compounds were also studied. The stability of free AN and AHAPs in vitro was investigated by plasma stability and storage stability tests. The interaction between AN and blank HA-g-PEG/ 偽-CD nanoparticles was studied by fluorescence experiment. Results the optimum temperature and pH value of AHAPs were 50 鈩，

本文編號：2410001