Microfluidic directed formation of liposomes of controlled size
Microfluidic directed formation of liposomes of controlled size
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DOI：
10.1021/la070051a
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发表时间：
2007-05-22
期刊：
影响因子：
3.9
通讯作者：
Gaitan, Michael
中科院分区：
文献类型：
--
作者：
Jahn, Andreas;Vreeland, Wyatt N.;Gaitan, Michael
提出了一种以微流控形式定制脂质体大小和分布的新方法。脂质体是由直径从几十纳米到几微米的脂双层形成的球形结构。脂质体的大小和大小分布是为特定的应用量身定做的，对于体内应用，如药物输送和基因治疗中的跨核膜转染，具有内在的重要性。传统的实验室脂质体制备方法需要后处理步骤，如超声波或膜挤压，以产生适当尺寸的制剂。在这里，我们描述了一种通过改变微流控通道中的流动条件来设计特定尺寸和尺寸分布的脂质体的方法，从而消除了后处理的需要。在微流控通道中，一股溶于酒精的脂状流在两个有鞘的水溶液之间进行流体力学聚焦。微通道中的层流允许在两个液体界面处进行受控的扩散混合，在那里脂类自组装成囊泡。用非对称流场-流动分级结合准弹性光散射和多角度激光散射对这种自组装过程形成的脂质体进行了表征。我们观察到，通过调整乙醇与水的体积流量的比例，泡囊的大小和大小分布在平均直径从50到150 nm范围内是可调节的。我们还观察到，脂质体的形成更依赖于聚焦的醇流宽度及其与水流的扩散混合，而不是溶剂-缓冲液界面的绝对作用力。
A new method to tailor liposome size and size distribution in a microfluidic format is presented. Liposomes are spherical structures formed from lipid bilayers that are from tens of nanometers to several micrometers in diameter. Liposome size and size distribution are tailored for a particular application and are inherently important for in vivo applications such as drug delivery and transfection across nuclear membranes in gene therapy. Traditional laboratory methods for liposome preparation require postprocessing steps, such as sonication or membrane extrusion, to yield formulations of appropriate size. Here we describe a method to engineer liposomes of a particular size and size distribution by changing the flow conditions in a microfluidic channel, obviating the need for postprocessing. A stream of lipids dissolved in alcohol is hydrodynamically focused between two sheathed aqueous streams in a microfluidic channel. The laminar flow in the microchannel enables controlled diffusive mixing at the two liquid interfaces where the lipids self-assemble into vesicles. The liposomes formed by this self-assembly process are characterized using asymmetric flow field-flow fractionation combined with quasi-elastic light scattering and multiangle laser-light scattering. We observe that the vesicle size and size distribution are tunable over a mean diameter from 50 to 150 nm by adjusting the ratio of the alcohol-to-aqueous volumetric flow rate. We also observe that liposome formation depends more strongly on the focused alcohol stream width and its diffusive mixing with the aqueous stream than on the sheer forces at the solvent-buffer interface.