Optimal self-assembly of lipid nanoparticles (LNP) in a ring micromixer.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
08 06 2022
08 06 2022
Historique:
received:
09
02
2022
accepted:
20
05
2022
entrez:
8
6
2022
pubmed:
9
6
2022
medline:
11
6
2022
Statut:
epublish
Résumé
Lipid nanoparticles (LNPs) for RNA and DNA delivery have attracted considerable attention for their ability to treat a broad range of diseases and to vectorize mRNA for COVID vaccines. LNPs are produced by mixing biomolecules and lipids, which self-assemble to form the desired structure. In this domain, microfluidics shows clear advantages: high mixing quality, low-stress conditions, and fast preparation. Studies of LNPs produced in micromixers have revealed, in certain ranges of flow rates, a degradation in performance in terms of size, monodispersity and encapsulation efficiency. In this study, we focus on the ring micromixer, which is well adapted to high throughput. We reveal three regimes, side-by-side, transitional and highly mixed, that control the mixing performance of the device. Furthermore, using cryo-TEM and biochemical analysis, we show that the mixing performances are strongly correlated to the characteristics of the LNPs we produce. We emphasize the importance of the flow-rate ratio and propose a physical criterion based on the onset of temporal instabilities for producing LNPs with optimal characteristics in terms of geometry, monodispersity and encapsulation yield. These criteria are generally applicable.
Identifiants
pubmed: 35676394
doi: 10.1038/s41598-022-13112-5
pii: 10.1038/s41598-022-13112-5
pmc: PMC9177731
doi:
Substances chimiques
Lipid Nanoparticles
0
Lipids
0
Liposomes
0
RNA, Small Interfering
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9483Informations de copyright
© 2022. The Author(s).
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