Evidence map›Paper›PMID 29182626›Full record

ArticlePloS one2017

Understanding the formation mechanism of lipid nanoparticles in microfluidic devices with chaotic micromixers.

Masatoshi Maeki, Yuka Fujishima, Yusuke Sato, Takao Yasui, Noritada Kaji, Akihiko Ishida, Hirofumi Tani, Yoshinobu Baba, Hideyoshi Harashima, Manabu Tokeshi

Abstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed.

  1. Article
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  4. Formulation of Peptide-Based Nanoparticles Using a Microfluidic Device.Journal of peptide science : an official publication of the European Peptide Society · 2026
    Article
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  6. Review
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  11. Article
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  16. Article
  17. Article
  18. Single particle charge detection mass spectrometry enables molecular characterization of lipid nanoparticles and mRNA packaging.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Article
  19. Article
  20. Article

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Masatoshi MaekiDivision of Applied Chemistry, Faculty of Engineering, Hokkaido University, Kita-ku, Sapporo, Japan.ORCID http://orcid.org/0000-0001-7500-4231
Yuka FujishimaGraduate School of Chemical Sciences and Engineering, Hokkaido University, Kita-ku, Sapporo, Japan.
Yusuke SatoFaculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Japan.
Takao YasuiDepartment of Applied Chemistry, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya, Japan.
Noritada KajiDepartment of Applied Chemistry, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya, Japan.
Akihiko IshidaDivision of Applied Chemistry, Faculty of Engineering, Hokkaido University, Kita-ku, Sapporo, Japan.
Hirofumi TaniDivision of Applied Chemistry, Faculty of Engineering, Hokkaido University, Kita-ku, Sapporo, Japan.
Yoshinobu BabaDepartment of Applied Chemistry, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya, Japan.
Hideyoshi HarashimaFaculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Japan.
Manabu TokeshiDivision of Applied Chemistry, Faculty of Engineering, Hokkaido University, Kita-ku, Sapporo, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Lab-On-A-Chip DevicesNanoparticlesLipidsMicroscopy, ConfocalLipids

Identifiers

PMID29182626
PMCPMC5705116

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.