Evidence map›Paper›PMID 37838143›Full record

ArticleEuropean journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V2023

The mixing method used to formulate lipid nanoparticles affects mRNA delivery efficacy and organ tropism.

Daria M Strelkova Petersen, Namit Chaudhary, Mariah L Arral, Ryan M Weiss, Kathryn A Whitehead

Open access · hybridAbstract read
In one paragraph

Article in European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
9.4field-weighted citation impact, top 1% of its field
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

34 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Post-loading ribonucleic acid into lipid nanoparticle carriers.bioRxiv : the preprint server for biology · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. DNA-directed assembly of multivalent lipid nanoparticles for targeted T cell gene delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Microfluidic Device Type Improves Heart mRNA DeliveryLangmuir : the ACS journal of surfaces and colloids · 2025
    Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Article
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

5 authors at 1 institution in 1 country.

Daria M Strelkova PetersenDepartment of Biomedical Engineering, Carnegie Mellon University, 5000, Forbes Ave, Pittsburgh, PA 15213, USA.
Namit ChaudharyDepartment of Chemical Engineering, Carnegie Mellon University, 5000, Forbes Ave, Pittsburgh, PA 15213, USA.
Mariah L ArralDepartment of Chemical Engineering, Carnegie Mellon University, 5000, Forbes Ave, Pittsburgh, PA 15213, USA.
Ryan M WeissDepartment of Chemical Engineering, Carnegie Mellon University, 5000, Forbes Ave, Pittsburgh, PA 15213, USA.
Kathryn A WhiteheadDepartment of Biomedical Engineering, Carnegie Mellon University, 5000, Forbes Ave, Pittsburgh, PA 15213, USA; Department of Chemical Engineering, Carnegie Mellon University, 5000, Forbes Ave, Pittsburgh, PA 15213, USA. Electronic address: kawhite@cmu.edu.
Carnegie Mellon University · US

Funding

Fate, Function and Genetic Engineering of Breast Milk Cells for Infant TherapyDP2HD098860 · NICHD · CARNEGIE-MELLON UNIVERSITY · PI WHITEHEAD, KATHRYN A. · 2018 to 2021
$2.4M
NICHD NIH HHS DP2 HD098860
6 · The paper itself

Abstract

mRNA is a versatile drug molecule with therapeutic applications ranging from protein replacement therapies to in vivo gene engineering. mRNA delivery is often accomplished using lipid nanoparticles, which are formulated via mixing of aqueous and organic solutions. Although this has historically been accomplished by manual mixing for bench scale science, microfluidic mixing is required for scalable continuous manufacturing and batch to batch control. Currently, there is limited understanding on how the mixing process affects mRNA delivery efficacy, particularly in regard to tropism. To address this knowledge gap, we examined the influence of the type of mixing and microfluidic mixing parameters on the performance of lipid nanoparticles in mice. This was accomplished with a Design of Experiment approach using four nanoparticle formulations with varied ionizable lipid chemistry. We found that each formulation required unique optimization of mixing parameters, with the total delivery efficacy of each lipid nanoparticle generated with microfluidics ranging from 100-fold less to 4-fold more than manually mixed LNPs. Further, mixing parameters influenced organ tropism, with the most efficacious formulations disproportionately increasing liver delivery compared to other organs. These data suggest that mixing parameters for lipid nanoparticle production may require optimization for each unique chemical formulation, complicating translational efforts. Further, microfluidic parameters must be chosen carefully to balance overall mRNA delivery efficacy with application-specific tropism requirements.

Indexed as

LiposomesNanoparticlesAnimalsGenetic TherapyMiceRNA, MessengerRNA, Small InterferingLipid NanoparticlesLiposomesRNA, MessengerRNA, Small InterferingBenchtop NanoAssemblrIonizable lipidsIVIS imagingLipid nanoparticlesLNPsMicrofluidics mixingmRNA deliveryRNA delivery

Identifiers

PMID37838143
PMCPMC10826902
OpenAlexW4387569822

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.