PMID- 35424092
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220416
IS  - 2046-2069 (Electronic)
IS  - 2046-2069 (Linking)
VI  - 11
IP  - 3
DP  - 2021 Jan 4
TI  - Three-dimensional, symmetrically assembled microfluidic device for lipid 
      nanoparticle production.
PG  - 1430-1439
LID - 10.1039/d0ra08826a [doi]
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.
CI  - This journal is (c) The Royal Society of Chemistry.
FAU - Kimura, Niko
AU  - Kimura N
AUID- ORCID: 0000-0002-6313-604X
AD  - Graduate School of Chemical Sciences and Engineering, Hokkaido University Kita 13 
      Nishi 8, Kita-ku Sapporo 060-8628 Japan +81-11-706-6745 +81-11-706-6744.
FAU - Maeki, Masatoshi
AU  - Maeki M
AUID- ORCID: 0000-0001-7500-4231
AD  - Division of Applied Chemistry, Faculty of Engineering, Hokkaido University Kita 
      13 Nishi 8, Kita-ku Sapporo 060-8628 Japan tokeshi@eng.hokudai.ac.jp 
      m.maeki@eng.hokudai.ac.jp +81-11-706-6745 +81-11-706-6745.
AD  - JST PRESTO 4-1-8 Honcho, Kawaguchi Saitama 332-0012 Japan.
FAU - Sasaki, Kosuke
AU  - Sasaki K
AD  - Faculty of Pharmaceutical Sciences, Hokkaido University Kita 12 Nishi 8, Kita-ku 
      Sapporo 060-0812 Japan.
FAU - Sato, Yusuke
AU  - Sato Y
AD  - Faculty of Pharmaceutical Sciences, Hokkaido University Kita 12 Nishi 8, Kita-ku 
      Sapporo 060-0812 Japan.
FAU - Ishida, Akihiko
AU  - Ishida A
AUID- ORCID: 0000-0003-4100-9426
AD  - Division of Applied Chemistry, Faculty of Engineering, Hokkaido University Kita 
      13 Nishi 8, Kita-ku Sapporo 060-8628 Japan tokeshi@eng.hokudai.ac.jp 
      m.maeki@eng.hokudai.ac.jp +81-11-706-6745 +81-11-706-6745.
FAU - Tani, Hirofumi
AU  - Tani H
AUID- ORCID: 0000-0002-5935-0756
AD  - Division of Applied Chemistry, Faculty of Engineering, Hokkaido University Kita 
      13 Nishi 8, Kita-ku Sapporo 060-8628 Japan tokeshi@eng.hokudai.ac.jp 
      m.maeki@eng.hokudai.ac.jp +81-11-706-6745 +81-11-706-6745.
FAU - Harashima, Hideyoshi
AU  - Harashima H
AD  - Faculty of Pharmaceutical Sciences, Hokkaido University Kita 12 Nishi 8, Kita-ku 
      Sapporo 060-0812 Japan.
FAU - Tokeshi, Manabu
AU  - Tokeshi M
AUID- ORCID: 0000-0002-4412-2144
AD  - Division of Applied Chemistry, Faculty of Engineering, Hokkaido University Kita 
      13 Nishi 8, Kita-ku Sapporo 060-8628 Japan tokeshi@eng.hokudai.ac.jp 
      m.maeki@eng.hokudai.ac.jp +81-11-706-6745 +81-11-706-6745.
AD  - Innovative Research Center for Preventive Medical Engineering, Nagoya University 
      Furo-cho, Chikusa-ku Nagoya 464-8601 Japan.
AD  - Institute of Nano-Life Systems, Institutes of Innovation for Future Society, 
      Nagoya University Furo-cho, Chikusa-ku Nagoya 464-8601 Japan.
LA  - eng
PT  - Journal Article
DEP - 20210105
PL  - England
TA  - RSC Adv
JT  - RSC advances
JID - 101581657
PMC - PMC8693528
COIS- The authors declare no competing financial interest.
EDAT- 2021/01/05 00:00
MHDA- 2021/01/05 00:01
PMCR- 2021/01/05
CRDT- 2022/04/15 05:27
PHST- 2020/10/16 00:00 [received]
PHST- 2020/12/09 00:00 [accepted]
PHST- 2022/04/15 05:27 [entrez]
PHST- 2021/01/05 00:00 [pubmed]
PHST- 2021/01/05 00:01 [medline]
PHST- 2021/01/05 00:00 [pmc-release]
AID - d0ra08826a [pii]
AID - 10.1039/d0ra08826a [doi]
PST - epublish
SO  - RSC Adv. 2021 Jan 5;11(3):1430-1439. doi: 10.1039/d0ra08826a. eCollection 2021 
      Jan 4.