Structure and morphology of vesicular dispersions based on novel glycophospholipids with various monosaccharide head groups

Journal article, 2026

Glycophospholipids combine the structural versatility of phospholipids and carbohydrates, but their potential as excipients and performance in other related applications remains largely unexplored due to their low natural abundance. We have synthesized four novel phosphatidyl saccharide conjugates with different carbohydrate head groups; glucose, galactose, fructose and xylose by using a Phospholipase D catalysed transphosphatidylation reaction. The combination of Small Angle X-ray Scattering (SAXS) and Cryogenic Transmission Electron Microscopy (cryo-TEM) data allowed us to characterize the dispersed glycophospholipid vesicles in excess water and under physiologically relevant solution conditions in terms of their morphology and structure. The different carbohydrate head group generated a large variability of the vesicle structures. Lipids conjugated with glucose and fructose self-assembled into unilamellar vesicles whereas galactose and xylose conjugated lipids formed multilamellar structures. Phosphatidylgalactose conjugated lipids formed a high number of stacked bilayers, while the phosphatidylxylose equivalent assembled into aggregates with only a few bilayers. These results highlight how carbohydrate hydroxyl spatial arrangements strongly influence lipid packing and self-assembly. The versatility of this glycophospholipid platform offers opportunities to generate biocompatible and biodegradable phospholipid excipients with properties that can be tailored for specific applications.