Interaction between Lamellar (Vesicles) and Nonlamellar Lipid Liquid-Crystalline Nanoparticles as Studied by Time-Resolved Small-Angle X-ray Diffraction

The kinetics of structure change when dispersions of two different types of lipid-based liquid-crystalline phases, one lamellar and one reversed, are mixed has been investigated using synchrotron small-angle X-ray diffraction and ellipsometry. The systems studied were (i) cubic-phase nanoparticles (CPNPs) based on glycerol monooleate (GMO) stabilized with a nonionic block copolymer, Pluronic F-127; (ii) CPNPs based on phytantriol (PtOH) stabilized with D-alpha-Tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS); and (iii) hexagonal-phase nanoparticles (HPNPs) based on a lipid mixture of diglycerol monooleate/glycerol dioleate, stabilized by Pluronic F-127. Time-resolved small-angle X-ray diffraction was used to track structural changes within nonlamellar nanoparticles when they interact with uni- and multilamellar vesicles of dioleoylphosphatidylcholine and dipalmitoylphatidylcholine. The results are very dependent on the type of nanoparticles under investigation. For GMO-based CPNPs, a strong interaction is observed on mixing with vesicular dispersions that leads to large changes in unit size dimensions as well as a later transition from cubic to lamellar structure. These results are in good agreement with previous studies on the interaction of GMO-based CPNPs with planar bilayers using neutron reflectivity, where the diffraction peak shifted with time upon mixing. The structural changes are much less prominent for the PtOH-based CPNPs and the HPNPs upon mixing with phospholipid vesicles. These results are correlated with those from measurement studying interactions between the liquid-crystalline nanoparticles and supported phospholipid bilayers by ellipsometry. Also, here the GMO-based CPNPs show more pronounced and rapid adsorption and interaction with the supported bilayer surface than do the other types of nonlamellar nanoparticles. The interaction also depends on the bilayer properties, where significantly slower lipid mixing is observed for a bilayer in the gel state compared to a bilayer in the liquid-crystalline phase. This study is not only relevant for drug-delivery applications but also shows the potential of synchrotron small-angle X-ray diffraction in studying time-dependent structural changes as a consequence of the interaction between different lipid self-assembled aggregates in complex systems.