Elucidation of lipid nanoparticle surface structure in mRNA vaccines

被引:23
作者
Wang, Mingzhang Maple [1 ]
Wappelhorst, Caitlin N. [1 ]
Jensen, Erika L. [1 ]
Chi, Ying-Chih Thomas [1 ]
Rouse, Jason C. [2 ]
Zou, Qin [1 ]
机构
[1] Pfizer Inc, Analyt Res & Dev, BioTherapeut Pharmaceut Sci, 875 Chesterfield Pkwy West, Chesterfield, MO 63017 USA
[2] Pfizer Inc, Analyt Res & Dev, BioTherapeut Pharmaceut Sci, 1 Burtt Rd, Andover, MA 01810 USA
关键词
POLYETHYLENE-GLYCOL; TRIGGERED RELEASE; NMR-SPECTROSCOPY; EX-VIVO; SIRNA; PH; IMPACT;
D O I
10.1038/s41598-023-43898-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Lipid nanoparticles (LNPs) have been used as a carrier for messenger RNA (mRNA) vaccines. Surface properties of LNPs are important to the stability and function of mRNA vaccines. Polyethylene-glycol (PEG) is a functional lipid at the surface of LNPs that improves colloidal stability, increases circulation time, and impacts cellular uptake. In this study, we explore in-depth lipid composition at the surface of mRNA-LNPs using high-field nuclear magnetic resonance (NMR) spectroscopy. Our results provide a unique surface lipid profile of intact LNPs identifying PEG chains and partial ionizable lipids are present with quantification capability. The surface PEG density is determined to reveal the brush-like conformation on the surface of mRNA-LNPs. Furthermore, we implement a diffusion NMR strategy for routine testing of formulated drug products during drug development. Comparative NMR analysis of different vaccine preparations and stability samples provides a global view of the mRNA-LNP surface structure for enhanced product knowledge.
引用
收藏
页数:8
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