Probing Molecular Packing of Lipid Nanoparticles from ³¹P Solution and Solid-State NMR

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 31 P nuclear magnetic resonance (NMR) methods to acquire structural and dynamic information about the phospholipid envelope of LNPs. Specifically, we demonstrate that the 31 P 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 31 P 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.

Enhanced electrochemical CO2-to-ethylene conversion through second-shell coordination on a Cu single-atom catalyst

“…S12†), revealing solely distinctive peaks corresponding to P–N. 52 Based on this inference, in the Cu–C 3 N 4 -HA, non-metallic elements substitute for C in the matrix, forming X–N coordination. Based on the aforementioned inference, it could be confirmed that in the constructed Cu–C 3 N 4 -HA, non-metallic elements substitute for C in the matrix, forming HA-N coordination.…”

Industrial Horizons in Pharmaceutical Science

“…In recent years, these tools have significantly advanced our understanding by pushing the boundaries in various areas. Examples include molecular or atomic level elucidation of key structures and interactions in amorphous solid dispersions within solid dosages, − critical (de)stabilizing interactions in parenteral peptide or protein formulations, − microenvironmental properties in lyophilized , and frozen biologics, and the encapsulation mechanisms of mRNA within LNPs for vaccine delivery. − These new applications exemplify the evolving mission of pharmaceutical sciences: to pose new questions to scientific and technical communities, to enhance collaboration, and to bring back innovative ideas and solutions. This dynamic approach helps drive forward the collective mission of delivering effective drugs to patients.…”