Department of Chemical Engineering, Indian Institute of Technology Bombay (IITB), Powai, Mumbai 400076, India.
Chem Phys Lipids. 2013 Jul-Aug;172-173:20-30. doi: 10.1016/j.chemphyslip.2013.04.006. Epub 2013 May 10.
Ethanol injection and variations of it are a class of methods where two miscible phases-one of which contains dissolved lipids-are mixed together leading to the self-assembly of lipid molecules to form liposomes. This method has been suggested, among other applications, for in situ synthesis of liposomes as drug delivery capsules. However, the mechanism that leads to a specific size selection of the liposomes in solution based self-assembly in general, and in flow-focussing microfluidic devices in particular, has so far not been established. Here we report two aspects of this problem. A simple and easily fabricated device for the synthesis of monodisperse unilamellar liposomes in a co-axial flow-focussing microfluidic geometry is presented. We also show that the size of liposomes is dependent on the extent of micro-convective mixing of the two miscible phases. Here, a viscosity stratification induced hydrodynamic instability leads to a gentle micro-mixing which results in larger liposome size than when the streams are mixed turbulently. The results are in sharp contrast to a purely diffusive mixing in macroscopic laminar flow that was believed to occur under these conditions. Further precise quantification of the mixing characteristics should provide the insights to develop a general theory for size selection for the class of ethanol injection methods. This will also lay grounds for obtaining empirical evidence that will enable better control of liposome sizes and for designing drug encapsulation and delivery devices.
乙醇注射和其变体是一类方法，其中两种可混溶的相 - 其中之一含有溶解的脂质 - 混合在一起，导致脂质分子自组装形成脂质体。除其他应用外，该方法还被提议用于原位合成脂质体作为药物输送胶囊。然而，导致基于溶液自组装的脂质体的特定大小选择的机制，一般来说，特别是在流聚焦微流控装置中，迄今尚未建立。在这里，我们报告了这个问题的两个方面。我们提出了一种简单且易于制造的装置，用于在同轴流聚焦微流控几何形状中合成单分散单层脂质体。我们还表明，脂质体的大小取决于两种可混溶相的微对流混合程度。在这里，由于粘度分层引起的流体动力学不稳定性导致温和的微混合，从而导致比当流股湍流混合时更大的脂质体尺寸。结果与在这些条件下被认为发生的宏观层流中的纯扩散混合形成鲜明对比。进一步精确量化混合特性应该为乙醇注射方法类的大小选择提供一般性理论的见解。这也将为获得经验证据奠定基础，从而能够更好地控制脂质体的大小，并为设计药物包封和输送装置提供依据。
