集成皮升微反应器和培养箱制备单分散脂质体

A. Hsieh, A. Lin, A.P. Lee
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引用次数: 0

摘要

提出了一种用于药物、血浆DNA、shRNA等药物和治疗应用的非病毒高效载体。其中以阳离子脂质为基础的脂质体载体一直是最具吸引力的非病毒解决方案。阳离子脂质与DNA复合物(脂质体)的大小决定了基因转染的效率。此外,在样品制备过程中,阳离子脂质与DNA的混合顺序、混合速率和混合孵育时间是决定脂质复合物大小的因素。我们开发了一种picoll微反应器和培养箱(PMRI)系统来制备单分散阳离子脂质和DNA复合物。在本实验室研制的微流控液滴形成装置的基础上,设计制作了单分散微反应器和培养箱。与传统的用手摇或旋涡混合的不可复制脂质体制备相比,我们开发的脂质体制备PMRI系统显示出同时快速均匀混合阳离子脂质和DNA的能力,并且产生更窄的尺寸分布峰和更小的平均尺寸。PMRI还使混合和孵育综合过程和脂聚物制剂的可重复性
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Monodisperse Lipoplex Generation by Integrated Picoliter Micro Reactor and Incubator
A non-viral and efficient carrier for the applications delivering drugs, plasmic DNA, shRNA for pharmaceutical and therapeutic applications is presented. The cationic lipid based liposomal carriers which has been the most attractive non-viral solution. The size of complexes of cationic lipid and DNA (lipoplex) dictates the efficiency of gene transfection. Moreover, the order of mixing of cationic lipid and DNA, mixing rate, and mixture incubation time are factors that determine the lipoplex sizes during sample preparation. We developed a Picoliter Micro Reactor and Incubator (PMRI) system to formulate monodisperse cationic lipids and DNA complexes. The monodisperse micro reactor and incubator was designed and fabricated based on the microfluidic droplet formation devices which developed by our lab and others. Compared with the conventional irreproducible lipoplex preparation using hand-shaking or vortexing processes for mixing, the PMRI system we developed for lipoplex formulation demonstrates the ability of rapid and uniformly mix cationic lipid and DNA simultaneously, and generates a narrower size distribution peak and smaller average size. The PMRI also enables the mixing and incubation integrated process and lipolex formulation reproducibility
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