Effects of High Pressure on Internally Self-Assembled Lipid Nanoparticles: A Synchrotron Small-Angle X-ray Scattering (SAXS) Study

Abstract

We present the first report on the effect of hydrostatic pressure on colloidally stabilized lipid nanoparticles enveloping inverse non-lamellar self-assemblies in their interiors. These internal self-assemblies were systematically tuned into bicontinuous cubic (Pn3m and Im3m), micellar cubic (Fd3m), hexagonal (H2), and inverse micellar (L2) phases by regulating the lipid-oil ratio while the hydrostatic pressure was varied from atmospheric pressure to 1200 bar, and back to the atmospheric pressure. The pressure effect on these lipid nanoparticles was compared with their equilibrium bulk, non-dispersed counterparts, i.e. inverse nonlamellar liquid crystalline phases and micellar solutions under excess water conditions using synchrotron small angle X-ray scattering (SAXS) technique. In the applied pressure-range, induced phase transitions were solely observed in fully hydrated bulk samples; whereas the internal self-assemblies of the corresponding lipid nanoparticles displayed only pressuremodulated single phases. Interestingly both, the lattice parameters and linear pressure expansion coefficients were larger for the self-assemblies enveloped inside the lipid nanoparticles as compared to the bulk states. This can in part be attributed to enhanced lipid layer undulations in the lipid particles in addition to induced swelling effects in presence of the tri-block copolymer F127. The bicontinuous cubic phases in both bulk state and inside lipid cubosome nanoparticles swell on compression, even so both keep swelling further on decompression at relatively high pressures before shrinking again at ambient pressures.Pressure dependence of the phases is also modulated by the concentration of the solubilized oil (tetradecane). These studies demonstrate the tolerance of lipid nanoparticles (cubosomes, hexosomes, micellar cubosomes, and emulsified microemulsions (EMEs)) for high pressures proving their robustness for various technological applications.3

Cubosomes: The Next Generation of Smart Lipid Nanoparticles?

“…The effects of temperature and pressure on cubic phases have been investigated in nanoparticle format. [97] Cubosomes composed of either phytantriol or Dimodan-U were mixed with different proportions of tetradecane oil to alter the phase morphology and dispersed with Pluronic F127 in water. They were compared with bulk mixtures which lacked the Pluronic F127 but that were all in excess water.…”

Cubic Liquid Crystalline Nanostructures Involving Catalase and Curcumin: BioSAXS Study and Catalase Peroxidatic Function after Cubosomal Nanoparticle Treatment of Differentiated SH-SY5Y Cells

“…Self-assembled lipid cubic phase (LCP) architectures comprise bilayer lipid membranes with a three-dimensional (3D) crystalline packing order and periodic networks of aqueous channels (Figure 1) [1,2,3,4,5,6]. The amphiphilic nature of the lyotropic liquid crystalline phases and nanoparticles (LCNPs) makes them suitable for the embedding of either lipophilic or hydrophilic guest compounds [7,8,9,10,11,12,13,14,15,16,17,18,19].…”

“…Regarding the lipid polymorphism, liquid crystalline phases have been formed by the self-assembly of hydrated mixtures of lyotropic lipids, co-lipids (oils or surfactants), and an aqueous phase, which may contain dissolved biomolecules (e.g., proteins, peptides or nucleic acids) [1,2,3,4,5,6,7,18,19,20,21,22,23,24,25,26,27,29,30,31,32,33,34,35,36]. Hydrated non-lamellar lipids (such as monoolein (MO)) can self-assemble into inverted bicontinuous cubic phases, bicontinuous sponge or inverted hexagonal phases depending on the experimental conditions and the applied stimuli [4,5,18,25,29,30,31,32].…”

“…Hydrated non-lamellar lipids (such as monoolein (MO)) can self-assemble into inverted bicontinuous cubic phases, bicontinuous sponge or inverted hexagonal phases depending on the experimental conditions and the applied stimuli [4,5,18,25,29,30,31,32]. Different types of bicontinuous cubic phases have been observed in lipid membranous systems [3,4,5,6,7,25,29]. Primitive (also referred to as Im3m /Q IIP ), double diamond ( Pn3m /Q IID ), and gyroid ( Ia3d /Q IIG ) cubic phases (Figure 1) are the most common ones for lyotropic monoglycerides.…”

A vesicle-to-sponge transition via the proliferation of membrane-linking pores in ω-3 polyunsaturated fatty acid-containing lipid assemblies

“…Liquid crystalline phase transformations of membranous assemblies are triggered by lipid monolayer curvature changes due to (i) the modifications of the degree of lipid hydration (concentration-driven transitions), (ii) the incorporation of co-lipids and hydrophobic guest molecules in the lipid bilayers or binding of soluble peptides (or other substances) at the membrane surface (composition-driven transitions), (iii) the biochemical processes (e.g. lipid oxidation, lipid hydrolysis, and other enzymatic reactions), or (iv) the application of environmental stimuli (temperature jumps, exposure to light, pressure, electrostatic effects, pH, etc) [2][3][4][38][39][40][41]. The molecular compositions, determining the properties of the lipid and amphiphile mixtures (lipid molecular shape, chain length, chain saturation, asymmetry of the hydrophobic moieties, headgroup polarity and size), govern the interfacial curvature and the elastic properties of the obtained membrane assemblies.…”