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Lipid nanoparticle properties explored using online asymmetric flow field-flow fractionation coupled with small angle X-ray scattering : Beyond average characterisation

Börjesdotter, Anna Maria LU ; Bolinsson, Hans LU orcid ; Dagø, Thomas ; Herranz-Trillo, Fátima LU ; Palmiero, Umberto Capasso ; Schagerlöf, Herje LU and Nilsson, Lars LU (2025) In International Journal of Pharmaceutics 668.
Abstract

This study employs asymmetric flow field-flow fractionation online coupled with small angle X-ray scattering at a synchrotron beamline, along with multiple downstream detectors, including multi-angle light scattering, dual wavelength UV and dRI. This setup enables size-resolved characterization of lipid nanoparticles, allowing for a detailed comparison between empty and cargo-loaded lipid nanoparticles intended for nucleic acid delivery. Batch-mode characterization techniques, including cryogenic transmission electron microscopy and dynamic light scattering, alongside collection of fractions for offline characterization with liquid chromatography-charged aerosol detection, allowed for determination of the particle morphology,... (More)

This study employs asymmetric flow field-flow fractionation online coupled with small angle X-ray scattering at a synchrotron beamline, along with multiple downstream detectors, including multi-angle light scattering, dual wavelength UV and dRI. This setup enables size-resolved characterization of lipid nanoparticles, allowing for a detailed comparison between empty and cargo-loaded lipid nanoparticles intended for nucleic acid delivery. Batch-mode characterization techniques, including cryogenic transmission electron microscopy and dynamic light scattering, alongside collection of fractions for offline characterization with liquid chromatography-charged aerosol detection, allowed for determination of the particle morphology, hydrodynamic radius, and the lipid composition over the size distribution. Cargo-containing and empty lipid nanoparticles show differences in density, and loaded particles exhibit a broader size distribution and a higher frequency of blebs at the surface. Both samples consist of spherical core–shell structured particles, with no distinguishable internal structure. A pivotal finding, often assumed until now, is that the mole fraction of each individual lipid component closely matches the original formulation. This work contributes to a more detailed understanding of lipid nanoparticles, supporting their continued development and rational design in medical applications.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Asymmetric flow field-flow fractionation, Drug delivery, Light scattering, Lipid nanoparticles, Size distribution, Size-resolved properties, small angle X-ray scattering
in
International Journal of Pharmaceutics
volume
668
article number
124940
publisher
Elsevier
external identifiers
  • pmid:39532273
  • scopus:85209358794
ISSN
0378-5173
DOI
10.1016/j.ijpharm.2024.124940
language
English
LU publication?
yes
id
50434deb-948f-4c01-8d52-de933aeaf95d
date added to LUP
2025-02-21 13:47:45
date last changed
2025-07-12 01:36:10
@article{50434deb-948f-4c01-8d52-de933aeaf95d,
  abstract     = {{<p>This study employs asymmetric flow field-flow fractionation online coupled with small angle X-ray scattering at a synchrotron beamline, along with multiple downstream detectors, including multi-angle light scattering, dual wavelength UV and dRI. This setup enables size-resolved characterization of lipid nanoparticles, allowing for a detailed comparison between empty and cargo-loaded lipid nanoparticles intended for nucleic acid delivery. Batch-mode characterization techniques, including cryogenic transmission electron microscopy and dynamic light scattering, alongside collection of fractions for offline characterization with liquid chromatography-charged aerosol detection, allowed for determination of the particle morphology, hydrodynamic radius, and the lipid composition over the size distribution. Cargo-containing and empty lipid nanoparticles show differences in density, and loaded particles exhibit a broader size distribution and a higher frequency of blebs at the surface. Both samples consist of spherical core–shell structured particles, with no distinguishable internal structure. A pivotal finding, often assumed until now, is that the mole fraction of each individual lipid component closely matches the original formulation. This work contributes to a more detailed understanding of lipid nanoparticles, supporting their continued development and rational design in medical applications.</p>}},
  author       = {{Börjesdotter, Anna Maria and Bolinsson, Hans and Dagø, Thomas and Herranz-Trillo, Fátima and Palmiero, Umberto Capasso and Schagerlöf, Herje and Nilsson, Lars}},
  issn         = {{0378-5173}},
  keywords     = {{Asymmetric flow field-flow fractionation; Drug delivery; Light scattering; Lipid nanoparticles; Size distribution; Size-resolved properties; small angle X-ray scattering}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{International Journal of Pharmaceutics}},
  title        = {{Lipid nanoparticle properties explored using online asymmetric flow field-flow fractionation coupled with small angle X-ray scattering : Beyond average characterisation}},
  url          = {{http://dx.doi.org/10.1016/j.ijpharm.2024.124940}},
  doi          = {{10.1016/j.ijpharm.2024.124940}},
  volume       = {{668}},
  year         = {{2025}},
}