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Updated: May 30, 2025
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Testing the In Vitro and In Vivo Efficiency of mRNA-Lipid Nanoparticles Formulated by Microfluidic Mixing
Published on: January 20, 2023
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Formulation screening of lyophilized mRNA-lipid nanoparticles
Anna Ruppl1, Denis Kiesewetter1, Monika Köll-Weber1
1Department of Pharmaceutics, Institute of Pharmaceutical Sciences, University of Freiburg, Sonnenstr. 5, Freiburg i. Br. 79104 Germany.
International Journal of Pharmaceutics
|January 28, 2025
Summary
New excipients stabilize freeze-dried messenger RNA lipid nanoparticles (mRNA-LNPs) for improved storage. Combinations of trehalose and PVP offer enhanced stability beyond the cold chain, crucial for mRNA therapeutics.
Area of Science:
- Biotechnology
- Pharmaceutical Sciences
- Materials Science
Background:
- Lipid nanoparticles (LNPs) are effective nucleic acid delivery systems, demonstrated during the COVID-19 pandemic.
- Long-term stability of mRNA-LNPs at refrigerated or higher temperatures remains a challenge for CMC development.
- Lyophilization (freeze-drying) is a potential method to improve LNP stability by water removal.
Purpose of the Study:
- To identify novel lyopreservatives for freeze-dried mRNA-LNP formulations beyond conventional sugars.
- To evaluate the stability of mRNA-LNPs with new protectants under various storage conditions.
- To guide formulation scientists in optimizing mRNA-LNP products for broader temperature stability.
Main Methods:
- Tested hydroxypropyl-beta-cyclodextrin, Kollidon® 12 PF (PVP), and dextran 40 kDa as potential lyopreservatives.
- Assessed formulations for particle size, polydispersity index (PDI), and encapsulation efficiency.
- Stored formulations for 6 months at 2-8°C, 25°C/60% RH, and 40°C/75% RH.
Main Results:
- Sucrose (10%) stabilized LNPs during lyophilization but not during subsequent storage at elevated temperatures.
- Formulations containing 9% trehalose + 1% PVP showed minimal size increase over 6 months at 25°C, maintaining PDI and encapsulation.
- Results were validated using eGFP-mRNA-LNPs and confirmed in cell culture experiments.
Conclusions:
- Trehalose and PVP combinations show promise for stabilizing mRNA-LNPs at higher temperatures, potentially eliminating the need for a cold chain.
- Optimized freeze-dried mRNA-LNP formulations can enhance the accessibility and usability of mRNA therapeutics.
- This research provides a foundation for developing more robust mRNA-LNP drug products.
