• 中国中文核心期刊
  • 中国科学引文数据库核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
高级检索

吸入用瑞德西韦脂质体的制备及其体外评价

赵笛, 李菁菁, 张凯, 秦超, 杨磊, 尹莉芳

赵笛, 李菁菁, 张凯, 秦超, 杨磊, 尹莉芳. 吸入用瑞德西韦脂质体的制备及其体外评价[J]. 中国药科大学学报, 2021, 52(5): 547-554. DOI: 10.11665/j.issn.1000-5048.20210506
引用本文: 赵笛, 李菁菁, 张凯, 秦超, 杨磊, 尹莉芳. 吸入用瑞德西韦脂质体的制备及其体外评价[J]. 中国药科大学学报, 2021, 52(5): 547-554. DOI: 10.11665/j.issn.1000-5048.20210506
ZHAO Di, LI Jingjing, ZHANG Kai, QIN Chao, YANG Lei, YIN Lifang. Preparation and in vitro characterization of remdesivir-loaded liposomes for inhalation[J]. Journal of China Pharmaceutical University, 2021, 52(5): 547-554. DOI: 10.11665/j.issn.1000-5048.20210506
Citation: ZHAO Di, LI Jingjing, ZHANG Kai, QIN Chao, YANG Lei, YIN Lifang. Preparation and in vitro characterization of remdesivir-loaded liposomes for inhalation[J]. Journal of China Pharmaceutical University, 2021, 52(5): 547-554. DOI: 10.11665/j.issn.1000-5048.20210506

吸入用瑞德西韦脂质体的制备及其体外评价

基金项目: 国家自然科学基金资助项目(No.81871477, No.81673377);重大新药创制国家科技重大专项资助项目(No.2017ZX09101001-004);中国药科大学新型冠状病毒肺炎应急科研专项资助项目(No.2632020ZX007)

Preparation and in vitro characterization of remdesivir-loaded liposomes for inhalation

Funds: This study was supported by the National Natural Science Foundation of China (No.81871477, No.81673377); China National Key Hi-Tech Innovation Project for the R&D of Novel Drugs (No.2017ZX09101001-004) and the Emergency Research Project for COVID-19 of China Pharmaceutical University (No.2632020ZX007)
  • 摘要: 制备吸入用瑞德西韦脂质体并对其体外性质进行评价。首先对瑞德西韦脂质体制备方法进行考察,通过单因素实验确定了制剂的处方组成和制备工艺。然后对瑞德西韦脂质体吸入剂的基本性质、体外沉积性质和空气动力学粒径等进行了全面评价。结果显示,以薄膜分散法制备并以pH 6.5磷酸盐缓冲液为水化介质制得的脂质体其粒径较小、包封率高、48 h几乎无沉淀产生。优化后的处方中药物与二棕榈酰磷脂酰胆碱(DPPC)的比例为1∶20,胆固醇占总脂材的10%,并加入20%二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000(DSPE-mPEG 2000)以提高脂质体稳定性。在冷冻干燥过程中加入4%海藻糖作为冻干保护剂,得到的冻干剂具有理想的外观并且复溶前后粒径变化较小、稳定性良好。透射电镜下观察到脂质体的微观形态呈表面光滑的球状结构,且粒径分布均匀。体外释放显示,经雾化器雾化前后脂质体混悬液的释放曲线无明显改变;体外沉积性质考察表明,使用新一代撞击器测得的细颗粒占51.4%,质量中值空气动力学粒径小于5 μm。实验结果表明,吸入用瑞德西韦脂质体具有良好的包封率和稳定性,雾化后的脂质体混悬液粒度分布均匀,能够有效地在肺部沉积,为新型冠状病毒肺炎的治疗提供了新的思路。
    Abstract: Remdesivir-loaded liposomes for inhalation were prepared and the in vitro properties were evaluated. Firstly, preparation methods of remdesivir-loaded liposomes were screened, and single-factor experiments were conducted to optimize the prescription and preparation process. Then the physical property, deposition ratio and aerodynamic particle size distribution of remdesivir-loaded liposomes suspension for inhalation were comprehensively evaluated. As a result, the optimal liposomes were prepared by the thin-film dispersion method with pH 6.5 phosphate-buffered saline as the hydration medium. In the prescription, the ratio of drug to DPPC was 1∶20; the cholesterol accounted for 10% of total lipids; and 20% DSPE-mPEG 2000 was added as stabilizer.4% trehalose was added as lyoprotectant when lyophilizing to obtain ideal appearance, good stability and a small particle size change after reconstitution. Remdesivir-loaded liposomes were spherical with smooth surface and uniform particle size distribution under transmission electron microscope. In vitro release tests showed no significant change for release curves of remdesivir-loaded liposomes suspension before and after nebulization. Deposition experiments indicated that the fine particles fraction of liposomes was 51.4%, and the mass median aerodynamic diameter was less than 5 μm measured by next generation impactor. To sum up, remdesivir-loaded liposomes for inhalation with high encapsulation efficiency and stability can achieve a suitable particle size distribution to effectively deposit in the lung after nebulization, which provides a new approach for the treatment of COVID-19.
  • [1] . J Biomol Struct Dyn,2021,39(10):3771-3779.
    [2] Wang RH,Zheng ZH,Zhang YQ,et al. Progress of research on immune escape mechanism of coronavirus[J]. J China Pharm Univ(中国药科大学学报),2021,52(1):1-9.
    [3] World Health Organization. WHO coronavirus disease (COVID-19) dashboard.[2021-02-18https://covid19.who.int.
    [4] Bao YF,Xue QR,Wu HP,et al. Advances in point-of-care testing for new Corona virus nucleic acid[J]. J China Pharm Univ(中国药科大学学报),2020,51(6):635-645.
    [5] Kokic G,Hillen HS,Tegunov D,et al. Mechanism of SARS-CoV-2 polymerase stalling by remdesivir[J]. Nat Commun,2021,12(1):279.
    [6] Sheahan TP,Sims AC,Graham RL,et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses[J]. Sci Transl Med,2017,9(396):eaal3653.
    [7] Wang M,Cao R,Zhang L,et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro[J]. Cell Res,2020,30(3):269-271.
    [8] Warren TK,Jordan R,Lo MK,et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys[J]. Nature,2016,531(7594):381-385.
    [9] Sun D. Remdesivir for treatment of COVID-19:combination of pulmonary and IV administration may offer aditional benefit[J]. AAPS J,2020,22(4):77.
    [10] Niven RW,Schreier H. Nebulization of liposomes. I. effects of lipid composition[J]. Pharm Res,1990,7(11):1127-1133.
    [11] National Pharmacopoeia Committee. Chinese Pharmacopoeia:Part 4(中华人民共和国药典:四部)[S]. Beijing:China Medical Science and Technology Press,2020:138-143.
    [12] U.S. Food and Drug Administration. FDA approves first treatment for COVID-19[EB/OL].(2020-10-22). https://www.fda.gov/news-events/press-announcements/fda - approves - first - treatment-covid-19.
    [13] Grein J,Ohmagari N,Shin D,et al. Compassionate use of remdesivir for patients with severe covid-19[J]. N Engl J Med,2020,382(24):2327-2336.
    [14] Veldhuizen R,Nag K,Orgeig S,et al. The role of lipids in pulmonary surfactant[J]. Biochim Biophys Acta,1998,1408(2/3):90-108.
    [15] Boni LT,Miller BS,Malinin V,et al. Sustained release of antiinfectives:
    US7718189[P]. 2010-05-18.
    [16] Siegel D,Hui HC,Doerffler E,et al. Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2,1-f][triazin-4-amino]adenine C-nucleoside (GS-5734) for the treatment of Ebola and emerging viruses[J]. J Med Chem,2017,60(5):1648-1661.
    [17] Wang XY,Gao L,Zhou Y,et al. Comparison of aerodynamic particle size distribution of salmeterol and fluticasone propionate powder for inhalation with the three impactors[J]. Chin J Pharm Anal(药物分析杂志),2020,40(1):186-197.
    [18] Wei NY,Zhou Y,Chen CC,et al. Determination of aerodynamic particle size distribution of ambroxol hydrochloride inhalation solution[J]. Chin J New Drugs(中国新药杂志),2018,27(17):1994-1998.
  • 期刊类型引用(9)

    1. 潘卫松,李克,吴健鸿,陈蓉. 吸入制剂辅料安全性评价的共性与个性. 医药导报. 2024(05): 752-756 . 百度学术
    2. 霍守雨,刘权辉,李卫清,黄奔. 益母草碱脂质体制备工艺的研究. 现代畜牧兽医. 2024(07): 7-12 . 百度学术
    3. 李广宝,张潇,杜林龙,贝阮婷,庞鑫. 纳米药物递送系统在肺部吸入给药中的研究进展. 中国医药工业杂志. 2024(10): 1343-1349 . 百度学术
    4. 王静文,文强,彭玉帅,赵文,尹利辉. 长效注射剂体外释药检查方法研究进展. 药物分析杂志. 2024(11): 1842-1851 . 百度学术
    5. 丁芷瑄,杨钰凤,舒薇. 脂质体肺部给药在抗菌药物中的应用. 海峡药学. 2023(01): 107-110 . 百度学术
    6. 宋波,黄莺,郭盈杉. 脂质体体外释放行为评价方法研究进展. 医药导报. 2023(03): 384-389 . 百度学术
    7. 朱狄峰,石萌,洪雅雯,赵剑岚,钱仁云. 高效液相色谱-串联质谱法分析硫酸特布他林雾化气溶胶含量及空气动力学粒径分布. 分析试验室. 2023(04): 521-527 . 百度学术
    8. 黄秋妹,阙慧卿,李唯,钱丽萍,刘经亮. 吴茱萸碱脂质体的制备工艺研究. 医学信息. 2023(19): 19-22 . 百度学术
    9. 张杰,杨琼梁,李欣,王颖彦,黄敏玲. 4种抗新型冠状病毒肺炎(COVID-19)药物在临床应用与分析. 中国临床药理学杂志. 2022(12): 1392-1397 . 百度学术

    其他类型引用(1)

计量
  • 文章访问数:  264
  • HTML全文浏览量:  8
  • PDF下载量:  584
  • 被引次数: 10
出版历程
  • 收稿日期:  2021-02-17
  • 修回日期:  2021-05-09
  • 刊出日期:  2021-10-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭