Characterization and associated pressure-dependent behavior of deposits formed during sterile filtration of mRNA-Lipid nanoparticles

The recent success of mRNA vaccines has generated increased interest in the use of Lipid Nanoparticles (LNPs) for delivery of nucleic acids. The objective of this study was to characterize the deposit formed on the surface of membranes during sterile filtration of mRNA-LNPs using a combination of scanning electron microscopy (SEM), environmental scanning electron microscopy (ESEM), atomic force microscopy (AFM), and hydraulic resistance measurements. The microscopic characterizations showed an amorphous deposit fouling the surface of the filter and blocking the membrane pores. The resistance of the deposit showed an unusual biphasic behavior, increasing at low pressure (consistent with a compressible filtration medium) but decreasing at high pressure, in a reversible manner. The surprising reduction in resistance at high pressure has not previously been identified in the filtration literature. The pressure corresponding to the maximum resistance (Pcritical) was found to be proportional to the inverse of the membrane pore size, as described by the Young-Laplace relationship. The hydraulic resistance measurements and microscopic characterization are consistent with a mechanism whereby an amorphous fouling deposit intrudes through membrane pores at high transmembrane pressures. These results provide important insights into the physical properties of the fouling deposit that governs the sterile filtration of LNPs.

© This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/

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Work Title Characterization and associated pressure-dependent behavior of deposits formed during sterile filtration of mRNA-Lipid nanoparticles
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Embargoed
Creators
  1. Kevork Oliver Messerian
  2. Anton Zverev
  3. Jack F. Kramarczyk
  4. Andrew L. Zydney
Keyword
  1. Lipid nanoparticle (LNP)
  2. mRNA vaccine
  3. Sterile filtration
  4. Fouling
  5. Compressibility
License CC BY-NC-ND 4.0 (Attribution-NonCommercial-NoDerivatives)
Work Type Article
Publisher
  1. Journal of Membrane Science
Publication Date July 4, 2023
Publisher Identifier (DOI)
  1. https://doi.org/10.1016/j.memsci.2023.121896
Deposited January 29, 2024

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Version 1
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  • Created
  • Added LNP_Resistance-_final.pdf
  • Added Creator Kevork Oliver Messerian
  • Added Creator Anton Zverev
  • Added Creator Jack F. Kramarczyk
  • Added Creator Andrew L. Zydney
  • Published
  • Updated Publication Date Show Changes
    Publication Date
    • 2023-10-15
    • 2023-07-04
  • Updated Keyword Show Changes
    Keyword
    • Lipid nanoparticle (LNP), mRNA vaccine, Sterile filtration, Fouling, Compressibility
  • Updated