| Research Abstract |
Novel aqueous dispersions of lipid nanoparticles with bicontinuous cubic (cubosomes) or hexagonal (hexosomes) liquid crystals in their interior were prepared by a high pressure emulsification. Small-angle X-ray scattering experiments confirmed the presence of cubic or hexagonal structures inside depend upon the monoolein/oleic acid-composition. ^13C NMR experiments with paramagnetic shift reagent showed that the signal of carbonyl carbon of oleic-1-^13C acid in the particles readily shifted to a lower magnetic field by addition of Eu^<3+>, indicating high accessibility of the ion into the water channel inside the particles. To understand behaviors in plasma of lipid nanoparticles; cubosomes, hexosomes, emulsions and vesicles, the effects of lipid composition and surface structure on the protein interaction were evaluated. Monoolein in cubosomes and hexosomes was extracted by plasma proteins and particles rapidly changed into sm emnants. Core lipids in emulsions played roles in determining the binding behavior of apolipoproteins A-1 and E at the particle surface: ^13C NMR and fluorescence measurements showed that the acyl chain region of phosphatidylcholine (PC) at emulsion surface monolayers is more restricted than those of vesicle PC bilayers, whereas the PC head group region of emulsions is more hydrated. Accordingly, interpenetration of core lipids into surface PC monolayers was presumed to occur in lipid emulsions. The interpenetration causes the separation of PC head groups and leads to enhanced apoA-1 or E binding at emulsion surface. Lipid risk factors, cholesterol, its ester, sphingomyelin and ceramide. modified the structure of surface monolayers, leading to the different protein binding and cell association.
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