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Updated: Sep 22, 2025

Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform
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Lipid nanoparticles with ionizable lipids: Statistical aspects.

Vladimir P Zhdanov1

  • 1Section of Nano and Biophysics, Department of Physics, Chalmers University of Technology, Göteborg, Sweden and Boreskov Institute of Catalysis, Russian Academy of Sciences, Novosibirsk, Russia.

Physical Review. E
|May 20, 2022
PubMed
Summary
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Lipid nanoparticles (LNPs) are crucial for drug delivery and vaccines. This study theoretically analyzes LNP protonation, charged LNP interactions with cell membranes, and LNP denaturation, providing insights into their complex behavior.

Area of Science:

  • Nanoscience
  • Biophysics
  • Materials Science

Background:

  • Lipid nanoparticles (LNPs) are vital for advanced drug and vaccine delivery systems.
  • Their efficacy relies on ionizable lipids that influence interactions with cell membranes.
  • Understanding LNP behavior at a molecular level is crucial for optimizing their function.

Purpose of the Study:

  • To theoretically investigate the protonation of ionizable lipids on LNPs.
  • To analyze the interaction dynamics between charged LNPs and supported lipid bilayers (SLBs).
  • To explore potential LNP denaturation mechanisms upon membrane interaction.

Main Methods:

  • Utilized phenomenological Langmuir-Stern and Poisson-Boltzmann models for LNP protonation.
  • Employed continuum and discrete charge distribution models.

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Last Updated: Sep 22, 2025

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  • Applied phenomenological theory and lattice-gas models to study LNP-SLB interactions.

    • Main Results:

    • Predicted Langmuirian H+ adsorption isotherms for ionizable lipids under specific conditions.
    • Demonstrated that opposite charges promote long-term association between LNPs and SLBs.
    • Provided a framework for estimating contact region size and lipid-lipid bonds in LNP-SLB interactions.

    Conclusions:

    • Theoretical models offer insights into LNP surface chemistry and membrane interactions.
    • Charge interactions are key drivers for LNP association with lipid bilayers.
    • Stepwise denaturation may occur during LNP-membrane interactions, impacting LNP stability.