Department of Pharmacy, University of Copenhagen, DK-2100 Copenhagen, Denmark.
Department of Pharmacy, University of Copenhagen, DK-2100 Copenhagen, Denmark.
Int J Pharm. 2020 Jun 15;583:119388. doi: 10.1016/j.ijpharm.2020.119388. Epub 2020 May 4.
Small interfering RNA (siRNA) is regarded as one of the most powerful tools for the treatment of various diseases by downregulating the expression of aberrant proteins. Delivery vehicle is often necessary for getting siRNA into the cells. Nanocomplex using polyamidoamine (PAMAM) is regarded a promising approach for the delivery of siRNA. The size of siRNA nanocomplexes is a critical attribute in order to achieve high gene silencing efficiency in vivo. Microfluidics provides advantages in the preparation of siRNA nanocomplexes due to better reproducibility and a potential for more robust process control. The mixing efficiency of siRNA and PAMAM is different in microfluidics systems with different geometries, therefore, resulting in nanocomplexes with varying size attributes. In this study, hydrodynamic flow focusing microfluidic chips with different channel designs, i.e. diameters/widths, channel shapes (cylindrical/rectangular) and inter-channel spacings were optimized in silico and rapidly prototyped using 3D printing and finally, used for production of siRNA nanocomplexes. The fluid mixing inside the microfluidic chips was simulated using the finite element method (FEM) with the single-phase laminar flow interface in connection with the transport of diluted species interface. The digital design and optimization of microfluidic chips showed consistency with experimental results. It was concluded that the size of siRNA nanocomplexes can be controlled by adjusting the channel geometry of the microfluidic chips and the simulation with FEM could be used to facilitate the design and optimization of microfluidic chips in order to produce nanocomplexes with desirable attributes.
小干扰 RNA（siRNA）被认为是通过下调异常蛋白表达来治疗各种疾病的最有力工具之一。为了将 siRNA 导入细胞，通常需要使用输送载体。使用聚酰胺-胺（PAMAM）的纳米复合物被认为是递送 siRNA 的一种很有前途的方法。为了在体内实现高基因沉默效率，siRNA 纳米复合物的大小是一个关键属性。微流控技术由于具有更好的重现性和更强大的过程控制潜力，因此在制备 siRNA 纳米复合物方面具有优势。由于不同几何形状的微流控系统中 siRNA 和 PAMAM 的混合效率不同，因此会导致具有不同大小属性的纳米复合物。在这项研究中，使用不同通道设计（即直径/宽度、通道形状（圆柱形/矩形）和通道间间距）的流体动力流聚焦微流控芯片进行了计算机模拟优化，并使用 3D 打印快速原型化，最后用于生产 siRNA 纳米复合物。使用有限元方法（FEM）模拟了微流控芯片内部的流体混合，其中单相层流界面与稀释物种界面的传输相关联。微流控芯片的数字设计和优化与实验结果一致。结论是，可以通过调整微流控芯片的通道几何形状来控制 siRNA 纳米复合物的大小，并且可以使用 FEM 模拟来辅助微流控芯片的设计和优化，以便生产具有理想属性的纳米复合物。
