Characterization of LNP Payload Distribution and Loading Percentage

October 13, 2026

9

min read

How nucleic acid cargo is distributed among lipid nanoparticles affects the dosage, efficacy, and safety of a vaccine or therapeutic. Size, zeta potential, and encapsulation efficiency can be measured with established techniques, but the proportion of particles that actually carry cargo is harder to determine, and no gold-standard method has been established.

Two Orthogonal Views of LNP Loading

This white paper, produced in collaboration with Spectradyne, compares cryo-TEM with single-particle fluorescence. Loaded particles show a grainy interior in cryo-TEM images, so analysts can classify them by eye, but that judgement is subjective. Quantitative textural analysis turns the same images into a measurement, and the results are compared against Spectradyne's ARC particle analyzer across two mRNA formulations, including deliberately mixed loaded and non-loaded samples.

What You’ll Learn in the White Paper

  • Which commercially available methods measure LNP loading percentage, and what each one detects
  • How textural analysis converts cryo-TEM images into a quantitative loading estimate
  • Whether loading status relates to particle size
  • How cryo-TEM results compare with the Spectradyne ARC particle analyzer, including specificity limits of each approach

Download the white paper for the full method, the data from both formulations, and practical guidance on combining techniques.

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