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通过微流控流体动力学聚焦法制备脂质体并同时负载药物模拟物。

Liposome production and concurrent loading of drug simulants by microfluidic hydrodynamic focusing.

作者信息

Lin Wan-Zhen Sophie, Malmstadt Noah

机构信息

Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, 925 Bloom Walk, HED 216, Los Angeles, CA, 90089-1211, USA.

Department of Biomedical Engineering, University of Southern California, 925 Bloom Walk, HED 216, Los Angeles, CA, 90089-1211, USA.

出版信息

Eur Biophys J. 2019 Sep;48(6):549-558. doi: 10.1007/s00249-019-01383-2. Epub 2019 Jul 20.

Abstract

Liposomes are spherical vesicles enclosed by phospholipid bilayers. Nanoscale liposomes are widely employed for drug delivery in the pharmaceutical industry. In this study, nanoscale liposomes are fabricated using the microfluidic hydrodynamic focusing (MHF) approach, and the effects of flow rate ratio (FRR) on liposome size and drug loading efficiency are studied. Fluorescein isothiocyanate modified dextran is used as a hydrophilic drug simulant and Nile red is used as a hydrophobic drug simulant. The experiment results show that hydrophilic drug simulant loading efficiency increases as FRR increases and eventually plateaues at around 90% loading efficiency. The hydrophobic drug simulant loading efficiency and FRR have a positive linear correlation when FRR varies from 10 to 50. Concurrent loading of both hydrophilic and hydrophobic drug simulants maintains the same loading efficiencies as those of loading each drug simulant alone. A negative correlation between liposome size and FRR is also confirmed. Unloaded liposomes and hydrophilic drug-loaded liposomes are of the same sizes, and are smaller than the ones loaded with the hydrophobic drug simulants alone or combined. The results suggest tunable liposome size and drug loading efficiency with the MHF technique. This provides evidence to encourage further studies of microfluidic liposome fabrication in the pharmaceutical industry.

摘要

脂质体是由磷脂双层包裹的球形囊泡。纳米级脂质体在制药行业中被广泛用于药物递送。在本研究中,采用微流控流体动力学聚焦(MHF)方法制备纳米级脂质体,并研究流速比(FRR)对脂质体大小和载药效率的影响。异硫氰酸荧光素修饰的葡聚糖用作亲水性药物模拟物,尼罗红用作疏水性药物模拟物。实验结果表明,亲水性药物模拟物的载药效率随FRR的增加而提高,最终在约90%的载药效率时趋于平稳。当FRR在10至50之间变化时,疏水性药物模拟物的载药效率与FRR呈正线性相关。同时加载亲水性和疏水性药物模拟物时,其载药效率与单独加载每种药物模拟物时相同。脂质体大小与FRR之间也存在负相关。未加载的脂质体和亲水性药物加载的脂质体大小相同,且小于单独或组合加载疏水性药物模拟物的脂质体。结果表明,利用MHF技术可调节脂质体大小和载药效率。这为鼓励在制药行业进一步研究微流控脂质体制备提供了证据。

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