| 摘要: |
| 目的 研究天冬酰胺酶磺丁基-β-环糊精超分子脂质纳米粒（ASLN）在大鼠体内的药代动力学行为，并初步探讨其对小细胞肺癌细胞增殖的抑制作用。方法 采用逆相蒸发法制备ASLN，考察其形态、粒径、zeta电位和包封率。12只SD大鼠随机分为2组，每组6只，分别静脉注射ASLN和游离天冬酰胺酶（Aase）2 kU/kg后，于48 h内的不同时间点取大鼠眼眶血测定血浆样品中Aase的活性，并绘制活性-时间曲线，采用DAS 2.1.1软件计算药代动力学参数。采用MTT法检测ASLN对小细胞肺癌细胞H446的细胞毒性作用。结果 ASLN呈球形或类球形，其粒径为（321.27±1.42）nm，zeta电位为（－9.31±0.42）mV，包封率为（66.46±1.57）%。ASLN和Aase的0～48 h活性-时间曲线 AUC分别为（199.48±2.18）、（57.63±3.89）U·mL－1·h，平均滞留时间分别为（4.40±0.05）、（2.09±0.07）h，峰浓度分别为（35.49±1.11）、（27.58±1.28）U/mL。ASLN相对Aase的生物利用度为325.96%。细胞毒性结果表明，ASLN对H446细胞具有增殖抑制作用，抑制率与其浓度呈正相关。结论 ASLN能改善Aase的药代动力学行为，提高Aase的生物利用度，并抑制小细胞肺癌细胞的增殖。 |
| 关键词: 天冬酰胺酶 超分子脂质纳米粒 药代动力学 生物利用度 小细胞肺癌 |
| DOI：10.16781/j.CN31-2187/R.20210092 |
| 投稿时间：2021-01-28修订日期：2022-03-07 |
| 基金项目:重庆市社会事业与民生保障科技创新专项（cstc2017shmsA130028）. |
|
| Pharmacokinetics and pharmacodynamics of asparaginase supramolecule lipidic nanoparticles in rats |
| WU Yan1,WAN Shengli2,LI Yao3,QIN Hong1,ZHANG Jingqing1* |
(1. Chongqing Research Center for Pharmaceutical Engineering, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China;
2. Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China;
3. Department of Pharmacy, Chongqing Public Health Medical Center, Chongqing 400036, China
* Corresponding author) |
| Abstract: |
| Objective To investigate the pharmacokinetic characteristics of asparaginase-loaded sulfobutyl ether-β-cyclodextrin supramolecule lipidic nanoparticles (ASLN) in rats and its inhibitory effect on the proliferation of small cell lung cancer cells. Methods ASLN were prepared by a reverse phase evaporation method, and their physicochemical properties, including morphology, particle size, zeta potential, and drug entrapment efficiency, were characterized. Twelve male Sprague-Dawley rats were randomly divided into 2 groups, with 6 rats in each group. After intravenous injection of ASLN and free asparaginase (Aase) 2 kU/kg, the activity of Aase in plasma samples was measured at different time points in 48 h, and the activity-time curve was drawn. The pharmacokinetic parameters were calculated by software DAS 2.1.1. The cytotoxicity of ASLN on H446 cells was explored by the MTT method. Results ASLN showed a spherical shape with a mean particle size of (321.27±1.42) nm, zeta potential of (－9.31±0.42) mV, and entrapment efficiency of (66.46±1.57) %. Pharmacokinetic parameters of ASLN and Aase were as follows: the area under curve (AUC(0-48 h)) (199.48±2.18) U·mL－1·h, (57.63±3.89) U·mL－1·h; the mean residence time (MRT(0-48 h)) (4.40±0.05) h, (2.09±0.07) h; and the peak concentration (Cmax) (35.49±1.11) U/mL, (27.58±1.28) U/mL. The relative bioavailability of ASLN to Aase was 325.96%. The cytotoxicity results indicated that ASLN had a proliferation inhibitory effect on H446 cells, and there was a positive correlation between the inhibition rate and the dose. Conclusion ASLN can improve the pharmacokinetics of Aase, enhance the bioavailability of Aase, and inhibit the proliferation of small cell lung cancer cells. |
| Key words: asparaginase supramolecule lipidic nanoparticles pharmacokinetics bioavailability small cell lung cancer |
