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柔性玉米醇溶蛋白纳米颗粒负载大麻二酚药代动力学研究*

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  • 中国中医科学院医学实验中心,北京市中医药防治重大疾病基础研究重点实验室,北京 100700
第一作者 Tel:(010)64089525;E-mail:y17860506421@163.com
** 范 斌 Tel:(010)64089535;E-mail:binf@263.net
聂颖兰 Tel:(010)64089536;E-mail:nyl100@163.com

收稿日期: 2023-04-03

  网络出版日期: 2024-06-21

基金资助

* 自然科学基金培育专项(JJPY2022007);国家自然科学基金青年科学基金项目(82104391);山东省泰山学者青年专家项目(tsqn202211360)

Study on the pharmacokinetics of cannabidiol supported by flexible zein nanoparticles*

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  • Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment of Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China

Received date: 2023-04-03

  Online published: 2024-06-21

摘要

目的:通过对负载大麻二酚(CBD)的柔性玉米醇溶蛋白纳米颗粒(FZP-CBD)和负载CBD的天然玉米醇溶蛋白纳米颗粒(NZP-CBD)在正常大鼠体内药代动力学研究,比较二者生物利用度的差异。方法:采用反溶剂法制备FZP-CBD和NZP-CBD,SD大鼠灌胃给予2组纳米制剂(CBD低、中、高3个剂量分别为20、50、100 mg·kg-1),在给药前及给药后0.5、1、1.5、2、3、4、6、8、10、12、24、48 h眼眶静脉丛采血,采用高效液相色谱-串联质谱法(HPLC-MS法)测定大鼠体内CBD的浓度,采用Waters Atlantis T3(100 mm×2.1 mm,3 μm)色谱柱;以0.1%甲酸水溶液为流动相A, 0.1%甲酸乙腈溶液为流动相B,梯度洗脱;流速0.3 mL·min-1;柱温30 ℃;进样量1 μL;检测以电喷雾电离源(ESI),正离子模式扫描,多反应监测模式(MRM)进行;用Winnonlin 8.1软件计算药动学相关参数。结果:FZP-CBD和NZP-CBD低、中、高3个剂量的Cmax分别为(414.8±184.1)、(715.3±191.7)、(1 798.4±854.5)和(240.6±143.8)、(542.3±235.4)、(1 173.3±317.0) μg·L-1,AUC0-t分别为(1 955.2±632.9)、(7 255.2±1 573.8)、(26 634.0±16 479.7)和(1 438.6±557.1)、(6 316.5±2 916.3)、(15 674.1±4 365.7) μg·h·L-1;与NZP-CBD相比,FZP-CBD低、中、高3个浓度Cmax分别提高了1.7、1.3、1.5倍,AUC0-t分别提高了1.4、1.1、1.7倍,生物利用度(F)分别提高了135.9%、114.9%、169.6%。结论:LC-MS测定方法专属性、灵敏度均能满足大鼠血清药动学测定。利用酸修饰制备的FZP-CBD相比NZP-CBD提高了CBD生物利用度,本研究可以提高CBD的利用价值,为CBD在医药学中的应用提供了新思路。

本文引用格式

孔艳, 焦玥, 彭娟, 吴晓霞, 聂颖兰, 范斌 . 柔性玉米醇溶蛋白纳米颗粒负载大麻二酚药代动力学研究*[J]. 药物分析杂志, 2023 , 43(10) : 1718 -1726 . DOI: 10.16155/j.0254-1793.2023.10.10

Abstract

Objective: To compare the difference on the bioavailability between cannabidiol (CBD)-loaded flexible zein nanoparticles (FZP-CBD) and CBD-loaded natural zein nanoparticles (NZP-CBD) by investigating the pharmacokinetics of both in normal rats. Methods: FZP-CBD and NZP-CBD were prepared by inverse-solvent method. SD rats were administrated with two groups of nano-preparations (the low, medium and high doses of CBD were 20, 50 and 100 mg·kg-1, respectively) by intragastric administration. Blood samples were collected from orbital venous plexus before and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 h after administration. The concentrations of CBD were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS), using Waters Atlantis T3 (100 mm×2.1 mm,3 μm) column, 0.1% formic acid-water as mobile phase A, 0.1% formic acid-acetonitrile as mobile phase B, gradient elution, at a flow rate of 0.3 mL·min-1, the column temperature was 30 ℃ and the injection volume was 1 μL. The detection was carried out by electrospray ionization source (ESI), positive ion mode scanning and multiple reaction monitoring (MRM) mode. Winnonlin 8.1 software was used to calculate the pharmacokinetic parameters. Results: The Cmax of low, medium and high concentration of FZP-CBD and NZP-CBD were (414.8±184.1) μg·L-1, ( 715.3±191.7) μg·L-1, (1 798.4±854.5) μg·L-1 and (240.6±143.8) μg·L-1, (542.3±235.4) μg·L-1, (1 173.3±317.0) μg·L-1, respectively. AUC0-t were (1 955.2±632.9) μg·h·L-1, (7 255.2±1 573.8) μg·h·L-1, (26 634.0±16 479.7) μg·h·L-1 and (1 438.6±557.1) μg·h·L-1, (6 316.5±2 916.3) μg·h·L-1, (15 674.1±4 365.7) μg·h·L-1, respectively. Compared with NZP-CBD, the Cmax of low, medium and high concentration of FZP-CBD increased by 1.7, 1.3 and 1.5 times respectively, and AUC0-t increased by 1.4, 1.1 and 1.7 times respectively, bioavailability(F) increased by 135.9%, 114.9%, 169.6% respectively. Conclusion: The specificity and sensitivity of LC-MS assay can satisfy the pharmacokinetic determination of rat serum. Compared with NZP-CBD, FZP-CBD prepared by acid modification can improve CBD bioavailability. This study can improve the utilization value of CBD and provide a new idea for the application of CBD in the area of medicine and pharmacy.

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