载天冬酰胺酶羟丙基-β-环糊精脂质体的理化特性和药代动力学  

Physicochemical properties and pharmacokinetics of hydroxypropyl-β-cyclodextrin liposomes containing L-asparaginase

作　　者：万胜利 何丹 晏子俊 李瑶 张景勍 WAN Sheng-li;HE Dan;YAN Zi-jun;LI Yao;ZHANG Jing-qing(Medicine Engineering Research Center,Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学药学院重庆高校药物工程研究中心

出　　处：《第二军医大学学报》2019年第6期700-703,共4页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(30973645)~~

摘　　要：目的考察载天冬酰胺酶羟丙基-β-环糊精脂质体(AHL)的理化性质及其在大鼠体内的药代动力学特性。方法采用逆相蒸发法制备AHL,考察其包封率、粒径、zeta电位和形态。取12只SD大鼠随机分成两组,分别尾静脉注射AHL和天冬酰胺酶(L-ASN),给药后定时眼眶下静脉丛取血,测定血浆样品中L-ASN的活性并绘制活性-时间曲线,采用DAS 2.1.1软件分析计算主要的药代动力学参数。结果AHL的平均包封率为(53.53±0.58)%,平均粒径为(388.99±2.02)nm,平均zeta电位为(-8.56±0.75)mV,透射电镜下观察为类球形。AHL的活性-时间曲线下面积大于L-ASN,AHL和L-ASN的0~48 h曲线下面积分别为(198.79±9.15)、(57.78±2.90)U/(mL?h),0~48 h平均滞留时间分别为(4.61±0.09)、(2.09±0.05)h,峰浓度分别为(32.32±1.33)、(26.82±1.38)U/mL,达峰时间分别为(1.08±0.20)、(0.10±0.04)h。AHL相对L-ASN的生物利用度为344.05%。结论AHL能改善L-ASN的药代动力学特性,提高其生物利用度。Objective To investigate the physicochemical properties and pharmacokinetics of L-asparaginase loaded hydroxypropyl-β-cyclodextrin liposome(AHL) in rats. Methods AHL was prepared by reverse evaporation method, and the entrapment rate, particle size, zeta potential and morphology of AHL were observed. Twelve SD rats were randomly divided into two groups. One group was injected with AHL, and the other group was injected with L-asparaginase(L-ASN). The blood samples were taken from infraorbital venous plexus, and the activity of L-ASN in the samples were determined and the activity-time curve was plotted. Main pharmacokinetic parameters were calculated by software DAS2.1.1. Results The average entrapment efficiency of AHL was(53.53±0.58)%, with an average particle size of(388.99±2.02) nm and an average zeta potential of(-8.56±0.75) mV. The pharmacokinetic parameters for AHL and L-ASN were: 0-48 h area under curve(198.79±9.15) U/(mL · h),(57.78±2.90) U/(mL · h);0-48 h mean resident time(4.61±0.09) h,(2.09±0.05) h;peak concentration(32.32±1.33) U/mL,(26.82±1.38) U/mL;and time to peak(1.08±0.20) h,(0.10±0.04) h, respectively. The relative bioavailability of AHL was 344.05%. Conclusion AHL can improve the pharmacokinetics and enhance the bioavailability of L-ASN.

关 键 词：天冬酰胺酶 羟丙基-β-环糊精脂质体 理化特性 药代动力学 

分 类 号：R943.4[医药卫生—药剂学]