Understanding the formation mechanism of lipid nanoparticles in microfluidic devices with chaotic micromixers.
Understanding the formation mechanism of lipid nanoparticles in microfluidic devices with chaotic micromixers.
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DOI：
10.1371/journal.pone.0187962
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Tokeshi M
中科院分区：
文献类型：
--
作者：
Maeki M;Fujishima Y;Sato Y;Yasui T;Kaji N;Ishida A;Tani H;Baba Y;Harashima H;Tokeshi M
脂质纳米粒（LNP）或脂质体是纳米医学中最广泛使用的药物载体。LNP的大小是影响药物递送效率和治疗效率的重要因素之一。在这里，我们展示了脂质浓度和混合性能对LNP尺寸的影响，使用微流体装置，目的是了解LNP形成机制并精确控制LNP尺寸。我们制作了具有不同深度（11 μm和31 μm）的混沌微混合器结构的微流控器件。根据LNP形成行为的结果，通过使用低浓度的脂质溶液和配备有31 μm混沌混合器结构的微流控装置，我们能够制备具有窄粒径分布的最小尺寸的LNP。我们还使用激光扫描共聚焦显微镜评估了微流体装置的混合速率，并且我们估计了用于控制LNP尺寸的临界乙醇浓度。临界乙醇浓度范围估计为60-80%乙醇。使用具有混沌混合器结构的微流体装置，实现了10纳米尺寸的LNP的调谐，以在临界浓度下获得最佳停留时间。对于30、40和50 nm尺寸的LNP，在控制LNP尺寸所需的临界浓度下的停留时间分别为10、15-25和50 ms时间尺度。最后，我们提出了LNP的形成机制的基础上确定的LNP的形成行为和临界乙醇浓度。由微流体装置产生的精确尺寸控制的LNP有望成为下一代纳米药物的载体，它们将为癌症治疗带来新的有效方法。
Lipid nanoparticles (LNPs) or liposomes are the most widely used drug carriers for nanomedicines. The size of LNPs is one of the essential factors affecting drug delivery efficiency and therapeutic efficiency. Here, we demonstrated the effect of lipid concentration and mixing performance on the LNP size using microfluidic devices with the aim of understanding the LNP formation mechanism and controlling the LNP size precisely. We fabricated microfluidic devices with different depths, 11 μm and 31 μm, of their chaotic micromixer structures. According to the LNP formation behavior results, by using a low concentration of the lipid solution and the microfluidic device equipped with the 31 μm chaotic mixer structures, we were able to produce the smallest-sized LNPs yet with a narrow particle size distribution. We also evaluated the mixing rate of the microfluidic devices using a laser scanning confocal microscopy and we estimated the critical ethanol concentration for controlling the LNP size. The critical ethanol concentration range was estimated to be 60–80% ethanol. Ten nanometer-sized tuning of LNPs was achieved for the optimum residence time at the critical concentration using the microfluidic devices with chaotic mixer structures. The residence times at the critical concentration necessary to control the LNP size were 10, 15–25, and 50 ms time-scales for 30, 40, and 50 nm-sized LNPs, respectively. Finally, we proposed the LNP formation mechanism based on the determined LNP formation behavior and the critical ethanol concentration. The precise size-controlled LNPs produced by the microfluidic devices are expected to become carriers for next generation nanomedicines and they will lead to new and effective approaches for cancer treatment.
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使用可调的微流体系统，细胞外纳米植物和凋亡体的分离。
影响因子：
4.6
作者：
Shin S;Han D;Park MC;Mun JY;Choi J;Chun H;Kim S;Hong JW
通讯作者：
Hong JW
影响因子：
64.8
作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Nielsen, Steven O.
影响因子：
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作者：
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通讯作者：
Yaghmur, Anan