TY - JOUR
T1 - Three-dimensional, symmetrically assembled microfluidic device for lipid nanoparticle production
AU - Kimura, Niko
AU - Maeki, Masatoshi
AU - Sasaki, Kosuke
AU - Sato, Yusuke
AU - Ishida, Akihiko
AU - Tani, Hirofumi
AU - Harashima, Hideyoshi
AU - Tokeshi, Manabu
N1 - Funding Information:
This work was supported by JST, CREST Grant Number JPMJCR17H1, Japan, JST, PRESTO Grant Number JPMJPR19K8, Japan, the Special Education and Research Expenses from the Ministry of Education, Culture, Sports, Science and Technology, Supporting Industry Program from the Small and Medium Enterprise Agency, JKA and its promotion funds from KEIRIN RACE, 2020 Feasibility Study Program of the Frontier Chemistry Center, Faculty of Engineering, Hokkaido University, JSPS KAKENHI Grant Number JP19J20939 and JP19KK0140, and Hosokawa Powder Technology Foundation. We would like to thank Editage (www.editage.com) for English language editing.
Publisher Copyright:
© 2021 The Royal Society of Chemistry.
PY - 2021/1/5
Y1 - 2021/1/5
N2 - Sub 100 nm-sized lipid nanoparticles (LNPs) have been widely used in drug delivery systems (DDSs). The size of the LNPs is an important parameter for the DDS performance, such as biodistribution and gene silencing using siRNAs. However, the LNPs prepared by the conventional preparation method show a wide size distribution. To improve the LNP size distribution, we developed a microfluidic device, named the iLiNP™ device, in a previous study. This device could produce LNPs in the size range of 20 to 150 nm, but the size distribution of the large-sized LNPs needs to be further improved. From the viewpoint of the LNP formation process, a homogeneous and slow rate dilution of ethanol plays an important role in improving the large-size LNP size distribution. In this study, we developed a three-dimensional, symmetrically assembled microfluidic device named the 3D-iLiNP device with the aim of precise size control of large-sized LNPs. We designed the 3D-iLiNP device using a computational fluid dynamics simulation and demonstrated that the 3D-iLiNP device can improve the LNP size distribution. The gene silencing activity of four kinds of siRNA-loaded LNPs was investigated via in vitro and in vivo experiments to elucidate the effect of the LNP size distribution. The results revealed that the LNPs with a size between 90 and 120 nm showed higher gene silencing activity than those with other sizes. The 3D-iLiNP device is expected to improve DDS performance by precisely controlling the size of LNPs.
AB - Sub 100 nm-sized lipid nanoparticles (LNPs) have been widely used in drug delivery systems (DDSs). The size of the LNPs is an important parameter for the DDS performance, such as biodistribution and gene silencing using siRNAs. However, the LNPs prepared by the conventional preparation method show a wide size distribution. To improve the LNP size distribution, we developed a microfluidic device, named the iLiNP™ device, in a previous study. This device could produce LNPs in the size range of 20 to 150 nm, but the size distribution of the large-sized LNPs needs to be further improved. From the viewpoint of the LNP formation process, a homogeneous and slow rate dilution of ethanol plays an important role in improving the large-size LNP size distribution. In this study, we developed a three-dimensional, symmetrically assembled microfluidic device named the 3D-iLiNP device with the aim of precise size control of large-sized LNPs. We designed the 3D-iLiNP device using a computational fluid dynamics simulation and demonstrated that the 3D-iLiNP device can improve the LNP size distribution. The gene silencing activity of four kinds of siRNA-loaded LNPs was investigated via in vitro and in vivo experiments to elucidate the effect of the LNP size distribution. The results revealed that the LNPs with a size between 90 and 120 nm showed higher gene silencing activity than those with other sizes. The 3D-iLiNP device is expected to improve DDS performance by precisely controlling the size of LNPs.
UR - http://www.scopus.com/inward/record.url?scp=85099380621&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85099380621&partnerID=8YFLogxK
U2 - 10.1039/d0ra08826a
DO - 10.1039/d0ra08826a
M3 - Article
AN - SCOPUS:85099380621
VL - 11
SP - 1430
EP - 1439
JO - RSC Advances
JF - RSC Advances
SN - 2046-2069
IS - 3
ER -