Measuring lipid nanoparticle cargo loading with partial specific volume distributions


  • Determining the drug amount in a lipid nanoparticle (LNP) poses a challenge, as the size and shape of the LNP may not necessarily indicate the actual drug content within.
  • Traditional techniques often falter in distinguishing between empty, partially loaded, or fully loaded LNPs, making accurate measurement problematic.


  • This technique offers precise bulk separation by identifying key properties like sedimentation and diffusion coefficients and solute concentrations.
  • For effective LNP loadings determination, both particle density discrimination and partial specific volume (PSV) are critical.
  • Density matching experiments, especially with D2O density matching, have been introduced. Different LNP loadings produce unique density profiles, facilitating differentiation.
  • Buffer density is fine-tuned using various D2O to H2O ratios.
  • Changes in sedimentation coefficients are tracked based on buoyancy.
  • SVEs under differing D2O:H2O buffer ratios are evaluated using UltraScan2, resulting in a g(s) distribution.
  • Normalized G(s) distributions are derived from these g(s) distributions, leading to the creation of a PSV distribution by extrapolating to S=0.
  • Experiments like sedimentation as a function of buoyancy g(s) are used to monitor changes in sedimentation coefficients.


  • Using variable buffer densities, specific PSV distributions can be obtained, which are pivotal in determining the loaded cargo in a mixture of liposomes.
  • These PSV distributions are instrumental in deducing properties like molar mass, density, anisotropy, and hydrodynamic radius distributions for mixtures.
  • For even greater precision in measurements, lowering the rotor speed can enhance the diffusion signal, ensuring meticulous and accurate analysis of LNPs and their drug content.
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Comparability Studies
Material Science (metal nanoparticles, synthetic polymers, drug compounds)

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