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Updated: Oct 6, 2025
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Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform
Published on: February 25, 2021
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Development of a high-throughput platform for screening lipid nanoparticles for mRNA delivery
Lili Cui1, Sara Pereira1, Silvia Sonzini1
1Advanced Drug Delivery, Pharmaceutical Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB21 6GH, UK. lili.cui@astrazeneca.com.
Nanoscale
|January 13, 2022
Summary
A new automated platform enables high-throughput screening of messenger RNA (mRNA) lipid nanoparticles (LNPs) for improved intracellular delivery. This technology accelerates the development of novel ionizable lipids and mRNA LNP candidates for preclinical applications.
Area of Science:
- Biotechnology and Pharmaceutical Sciences
- Nanomedicine and Drug Delivery Systems
Background:
- Messenger RNA (mRNA) lipid nanoparticles (LNPs) are crucial for intracellular nucleic acid delivery, highlighted by COVID-19 vaccines.
- Optimizing LNP formulations requires systematic evaluation of ionizable, PEG, structural, and helper lipids.
- Current *in vitro* screening methods for novel lipids and LNP compositions are hindered by low-throughput LNP preparation.
Purpose of the Study:
- To present an automated, high-throughput screening platform for selecting novel ionizable lipids and mRNA-encapsulating LNPs *in vitro*.
- To overcome the limitations of low-throughput LNP preparation in lipid and LNP composition screening.
Main Methods:
- Development and implementation of a lab-based automated liquid handling system for high-throughput LNP preparation (up to 384 formulations per plate).
- Precise mixing and reproducible preparation of mRNA LNPs to enable direct head-to-head comparison of numerous formulations.
- Integration of the platform into a fully-automated workflow for LNP property control, physicochemical characterization, and biological evaluation.
Main Results:
- The automated platform successfully screened novel mRNA LNPs, identifying lead candidates comparable to those from microfluidics technology (correlation coefficient of 0.8751).
- The high-throughput screening significantly narrows down the number of novel ionizable lipids requiring *in vivo* evaluation.
- The robotic process demonstrated high reproducibility and precision in mRNA LNP preparation.
Conclusions:
- The developed high-throughput platform effectively facilitates the screening and selection of novel ionizable lipids and mRNA LNPs.
- This automated system accelerates proprietary lipid development and mRNA LNP lead optimization for preclinical applications.
- The platform has the potential to expedite the advancement of mRNA LNP candidates to meet urgent global health needs.
