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Updated: Jun 10, 2025
Author Spotlight: Enhancing Lipid Nanoparticle Formation Through Turbulent Mixing in Confined Geometries
Published on: August 23, 2024
Production of mRNA lipid nanoparticles using advanced crossflow micromixing
Muattaz Hussain1, Burcu Binici1, Liam O'Connor1
1Strathclyde Institute of Pharmacy and Biomedical Sciences, 161 Cathedral St., University of Strathclyde, Glasgow, G4 0RE, United Kingdom.
Objectives:
Lipid nanoparticles (LNPs) play a crucial role in RNA-based therapies, and their production is generally based on nanoprecipitation and coalescence of lipids around an RNA core. This study investigated crossflow micromixing to prepare LNPs across various mixing ratios and production speeds.
Methods:
A range of LNPs were prepared using crossflow micromixing across production speeds of 10-500 ml/min, and their physico-chemical characteristics (size, polydispersity index (PDI), zeta potential, and mRNA encapsulation), in vitro mRNA expression and in vitro efficacy (protein expression and antibody and cytokine responses).
Key Findings:
Our results demonstrate the reproducible production of mRNA-LNPs with controlled critical quality attributes, including high mRNA encapsulation from the initial screening scale through to GMP-scale production, where the same mixing ratio can be adopted across all product speeds from 30 to 500 ml/min used.
Conclusions:
We confirm the applicability of stainless-steel crossflow membrane micromixing for the entire spectrum of mRNA-LNP production, ranging from initial discovery volumes to GMP-production scale.
