1 research outputs found
Probing Molecular Packing of Lipid Nanoparticles from <sup>31</sup>P Solution and Solid-State NMR
Lipid
nanoparticles (LNPs) are intricate multicomponent systems
widely recognized for their efficient delivery of oligonucleotide
cargo to host cells. Gaining insights into the molecular properties
of LNPs is crucial for their effective design and characterization.
However, analysis of their internal structure at the molecular level
presents a significant challenge. This study introduces 31P nuclear magnetic resonance (NMR) methods to acquire structural
and dynamic information about the phospholipid envelope of LNPs. Specifically,
we demonstrate that the 31P chemical shift anisotropy (CSA)
parameters serve as a sensitive indicator of the molecular assembly
of distearoylphosphatidylcholine (DSPC) lipids within the particles.
An analytical protocol for measuring 31P CSA is developed,
which can be implemented using either solution NMR or solid-state
NMR, offering wide accessibility and adaptability. The capability
of this method is demonstrated using both model DSPC liposomes and
real-world pharmaceutical LNP formulations. Furthermore, our method
can be employed to investigate the impact of formulation processes
and composition on the assembly of specifically LNP particles or,
more generally, phospholipid-based delivery systems. This makes it
an indispensable tool for evaluating critical pharmaceutical properties
such as structural homogeneity, batch-to-batch reproducibility, and
the stability of the particles