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

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 ( 31 P) is a particularly sensitive and non-destructive approach because phospholipid components have one 31 P nucleus per molecule. Here, we demonstrate quantitative observations of individual phospholipids in intact liposomes via solution 31 P-NMR. In addition, the 31 P 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, 31 P-NMR can be used to analyze phospholipids in liposomes and related pharmaceutical preparations for quality control.