Probing Molecular Packing of Lipid Nanoparticles from 31P Solution and Solid-State NMR.
Anal Chem
; 96(6): 2464-2473, 2024 02 13.
Article
en En
| MEDLINE
| ID: mdl-38306310
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Nanopartículas
/
Liposomas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Anal Chem
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos