Adsorption of Lipid Liquid Crystalline Nanoparticles: Effects of Particle Composition, Internal Structure, and Phase Behavior

Abstract

Controlling the interfacial behavior and properties of lipid liquid crystalline nanoparticles (LCNPs) at surfaces is essential for their application for preparing functional surface coatings as well as understanding some aspects of their properties as drug delivery vehicles. Here we have studied a LCNP system formed by mixing soy phosphatidylcholine (SPC), forming liquid crystalline lamellar structures in excess water, and glycerol dioleate (GDO), forming reversed structures, dispersed into nanoparticle with the surfactant polysorbate 80 (P80) as stabilizer. LCNP particle properties were controlled by using different ratios of the lipid building blocks as well as different concentrations of the surfactant P80. The LCNP size, internal structure, morphology, and charge were characterized by dynamic light scattering (DLS), synchrotron small-ange X-ray scattering (SAXS), cryo-transmission electron microscopy (cryo-TEM), and zeta potential measurements, respectively. With increasing SPC to GDO ratio in the interval from 35:65 to 60:40, the bulk lipid phase structure goes from reversed cubic micellar phase with Fd3m space group to reversed hexagonal phase. Adding P80 results in a successive shift toward more disorganized lamellar type of structures. This is also seen from cryo-TEM images for the LCNPs, where higher P80 ratios results in more extended lamellar layers surrounding the inner, more dense, lipid-rich particle core with nonlamellar structure. When put in contact with a solid silica surface, the LCNPs adsorb to form multilayer structures with a surface excess and thickness values that increase strongly with the content of P80 and decreases with increasing SPC:GDO ratio. This is reflected in both the adsorption rate and steady-state values, indicating that the driving force for adsorption is largely governed by attractive interactions between poly(ethylene oxide) (PEO) units of the P80 stabilizer and the silica surface. On cationic surface, i.e., silica modified with 3-aminopropltriethoxysilane (APTES), the slightly negatively charged LCNPs give rise to a very significant adsorption, which is relatively independent of LCNP composition. Finally, the dynamic thickness measurements indicate that direct adsorption of intact particles occurred on the cationic surface, while a slow buildup of the layer thickness with time is seen for the weakly interacting systems.

Structural effects of the dispersing agent polysorbate 80 on liquid crystalline nanoparticles of soy phosphatidylcholine and glycerol dioleate

“…1,7 Consistent with the enrichment of GDO in the core and consequently lower degree of hydration, the lattice parameter obtained from SAXD data ( Figure 1) and the fitted particle core diameter decrease with increasing d-P80 concentration ( Figure 4, Table 2) . As previously mentioned, phase separation has been proposed to occur at higher d-P80 concentrations.…”

“…Such a phase would be less hydrated, as is obvious from the phase diagram. 1 7 As a distinct inner Fd3m structure was observed by SAXD for the 5% d-P80 LCNPs (Figure 1), the fraction of d-P80 is probably less than 5 % in the particle core. Here it should be noted that the resolution of the fit does not allow for a more detailed estimation of the fraction of d-P80 solubilized in the core.…”

“…The Fd3m structure of the bulk 50/50 SPC/GDO phase was previously shown to be preserved in the LCNPs dispersed with 5-10 % P80, although such P80 concentrations, when mixed into the bulk SPC/GDO phase, cause transformations into an intermediate phase structure or phase mixtures. 1,7 The polymeric surfactant was therefore proposed to reside mainly at the surface of the particles. However, an increased fraction of P80 did indeed result in a reduced lattice constant in the 5-10 % P80 LCNPs and at 15 % P80 the inner structure was eventually transformed into a disordered micellar phase (L 2 ), as shown by small angle X-ray diffraction (SAXD).…”

“…For instance, for LCNPs serving as drug delivery vehicles, adsorption of material to the storage container, catheters and other delivery devices must be minimized, while systems designed for surface modifying applications would require maximal adsorption. Studies of the interaction of different LCNPs with supported model lipid membranes 4,7,9,11,12 , vesicles 2 and blood 2,13,14 have helped to explain the characteristic interactions of the particles with biological interfaces and components. We have previously studied the interaction of both SPC/GDO 7,9 and GMO 11,15 based LCNPs with silicon surfaces, either in the natural hydrophilic state or rendered hydrophobic or cationic.…”

Orientation specific deposition of mesoporous particles

“…The cationic silica surfaces were prepared by liquid phase silanization of the virgin silica surfaces 12 described above. The silica surfaces were dried in a flow of nitrogen gas and then plasma cleaned (Harrick Scientific Corp., model PDC-3XG) for 5 min at 0.04 millibars to remove any organic contaminants, followed by drying in an oven at 150 • C for 30 min to remove any moisture.…”