Session: Session 4

Exploring the Spatial Distribution of mRNA-Lipid Nanoparticles in Mouse Whole-Body and Isolated Organs Using MALDI MSI

INTRODUCTION

Studying biodistribution of lipid nanoparticles (LNPs) used for delivery of mRNA-based treatments is essential to improve their composition and ensure safe, effective drug delivery. This study monitored lipid components of mRNA-LNPs in mice, analyzing their distribution in whole bodies and specific organs using MALDI-MSI.

METHODOLOGY

We examined male and female mice at various times after administering mRNA-LNPs (LNP1 and LNP2). Organ sections were prepared on ITO slides for mass spectrometry imaging (MSI). Sagittal sections targeted the liver, kidney, pancreas, spleen, lung, heart, and testis. MSI data were analyzed by MultimagingTM from Aliri France SAS. Histological analysis used NDP.view2 by Hamamatsu. The MSI signal was normalized using an internal standard before measuring the test substances' concentration in µg/g of each histological structure.

RESULTS

LNP1 showed a strong, lasting presence in both male and female mice, detectable up to 168 hours post-administration in females and 72 hours in males. It quickly distributed to organs like the spleen, liver, kidney, heart, and intestines, with high exposure in the liver and spleen. Tissue half-lives in females ranged from 57 to 88 hours, while in males they ranged from 30 to 168 hours, with minimal clearance in the liver and spleen. LNP2 was undetectable in female whole-body sections or organs by the 6-hour mark, suggesting limited distribution, rapid metabolism, or insufficient sensitivity.

CONCLUSION

The study shows that LNP1 has a prolonged presence and broad organ distribution in mice, especially in the liver and spleen. Significant pharmacokinetic differences between genders necessitate further detailed studies. The absence of detectable LNP2 in early female assessments suggests possible sensitivity limitations of the technique for this component, warranting additional investigation. These findings underscore the need for thorough preclinical evaluations of lipid nanoparticle-based therapies.