Quantitative lipid composition characterization of intact liposomes via 31P nuclear magnetic resonance spectroscopy

Abstract

Drug delivery systems (DDS) are important methods to maximize drug efficacy by enabling in vivo accumulation at the target site. Liposomes, which are nanoscale vesicles consisting of lipid bilayers, are widely used for clinical DDS. The lipid composition of an intact liposome is a significant factor that directly affects its characteristics and functions. Thus, it is important to develop quantitative or qualitative analytical methods to characterize the lipid composition. Nuclear magnetic resonance (NMR) of phosphorus (31P) is a particularly sensitive and non-destructive approach because phospholipid components have one 31P nucleus per molecule. Here, we demonstrate quantitative observations of individual phospholipids in intact liposomes via solution 31P-NMR. In addition, the 31P linewidths became narrower if the liposomes contained > 10 mol% of polyethylene glycol-(PEGylated) phospholipids, which also contributed to liposome down-sizing. Down-sizing and PEGylation are important strategies for efficient drug delivery. Hence, 31P-NMR can be used to analyze phospholipids in liposomes and related pharmaceutical preparations for quality control. Graphical abstract: (Figure presented.)