The Use of a Microfluidic Device to Encapsulate a Poorly Water-Soluble Drug CoQ10 in Lipid Nanoparticles and an Attempt to Regulate Intracellular Trafficking to Reach Mitochondria
The Use of a Microfluidic Device to Encapsulate a Poorly Water-Soluble Drug CoQ10 in Lipid Nanoparticles and an Attempt to Regulate Intracellular Trafficking to Reach Mitochondria
复制标题
DOI：
10.1016/j.xphs.2019.04.001
复制
发表时间：
2019-08-01
影响因子：
3.8
通讯作者：
Harashima, Hideyoshi
中科院分区：
文献类型：
--
作者：
Hibino, Mitsue;Yamada, Yuma;Harashima, Hideyoshi
目前市场上的许多药物以及新的候选药物都是水溶性差的。正因为如此，需要开发将允许这些药物的扩展使用的药物制剂。使用脂质体和脂质纳米颗粒进行药物递送作为用于溶解水溶性差的分子的技术已经引起了关注，但是该技术面临严重的放大风险。在这项研究中，我们报告了将辅酶Q（10）（CoQ（10））作为水溶性差的药物模型封装在MITO-Porter中的尝试，MITO-Porter是一种使用微流体装置（CoQ（10）-MITO-Porter [mu]）进行线粒体递送的脂质体。将CoQ（10）-MITO-Porter [mu]的物理性质（包括均匀性、大小和制备体积）与通过乙醇稀释法制备的CoQ（10）-MITO-Porter（CoQ 10-MITO-Porter [艾德]）的物理性质进行比较。在使用微流体装置的情况下，均匀地形成小尺寸的CoQ（10）-MITO-Porter，并且可以大规模制备它。使用HeLa细胞进行的细胞内观察显示，CoQ（10）-MITO-Porter [mu]被细胞有效内化以到达线粒体。这些结果表明CoQ（10）-MITO-Porter [mu]代表了用于线粒体纳米医学的潜在候选者。(C)2019由Elsevier Inc.出版代表美国药剂师协会
A number of drugs that are currently on the market, as well as new candidates for drugs, are poorly water soluble. Because of this, a need exists to develop drug formulations that will permit the expanded use of such drugs. The use of liposomes and lipid nanoparticles for drug delivery has attracted attention as a technique for solubilizing molecules that are poorly water soluble, but this technique faces serious scale-up risks. In this study, we report on attempts to encapsulate Coenzyme Q(10) (CoQ(10)) as a model of a poorly water-soluble drug in an MITO-Porter, a liposome for mitochondrial delivery using a microfluidic device (a CoQ(10)-MITO-Porter [mu]). The physical properties of the CoQ(10)-MITO-Porter [mu] including homogeneity, size, and preparation volume were compared with those for a CoQ(10)-MITO-Porter prepared by the ethanol dilution method (a CoQ10-MITO-Porter [ED]). In the case where a microfluidic device was used, a small-sized CoQ(10)-MITO-Porter was formed homogeneously, and it was possible to prepare it on a large scale. Intracellular observations using HeLa cells showed that the CoQ(10)-MITO-Porter [mu] was efficiently internalized by cells to reach mitochondria. These results indicate that the CoQ(10)-MITO-Porter [mu] represents a potential candidate for use in mitochondrial nanomedicine. (C) 2019 Published by Elsevier Inc. on behalf of the American Pharmacists Association.