A Simple Evaporation Method for Large-Scale Production of Liquid Crystalline Lipid Nanoparticles with Various Internal Structures

Abstract

We present a simple and industrially accessible method of producing liquid crystalline lipid nanoparticles with various internal structures based on phytantriol, Pluronic F127, and vitamin E acetate. Bilayer vesicles were produced when an ethanolic solution dissolving the lipid components was mixed with deionized water. After the evaporation of ethanol from the aqueous mixture, vesicles were transformed into lipid-filled liquid crystalline nanoparticles with well-defined internal structures such as hexagonal lattices (mostly inverted cubic Pn3m), lined or coiled pattern (inverted hexagonal H2), and disordered structure (inverse microemulsion, L2), depending on the compositions. Further studies suggested that their internal structures were also affected by temperature. The internal structures were characterized from cryo-TEM and small-angle X-ray scattering results. Microcalorimetry studies were performed to investigate the degree of molecular ordering/crystallinity of lipid components within the nanostructures. From the comparative studies, we demonstrated the present method could produce the lipid nanoparticles with similar characteristics to those made from a conventional method. More importantly, the production only requires simple tools for mixing and ethanol evaporation and it is possible to produce 10 kg or so per batch of aqueous lipid nanoparticles dispersions, enabling the large-scale production of the liquid crystalline nanoparticles for various biomedical applications.

Free‐Standing Phytantriol Q224 Cubic‐Phase Films: Resistivity Monitoring and Switching

“…The onset, peak, and offset temperatures for the phase transition can be found (Figure B) as well as the enthalpy (estimated here as 0.5 mJ mg −1 or 150 J mol −1 based on phytantriol) from integrating the heat capacity curve (Figure C). Literature microcalorimetry data for phytantriol mesophase systems were reported by Doo‐Hoon on cubosomes. However, transition data were not unequivocally assigned as cubic to hexagonal.…”

Factors affecting the structure of lyotropic liquid crystals and the correlation between structure and drug diffusion

“…The dispersed hexosomes were successfully prepared by Kim et al when adding VitEA to PT-Pluronic F-127 (stabilizer)-water systems. 79 The inuence of hexadecane in PT and GMO was investigated respectively by Phan et al 22 SAXS data indicated that in GMOwater systems at 25 C, Pn3m, H 2 , micellar cubic phase (Fd3m), and inversed micelles (L 2 ) appeared when the concentration of hexadecane was 0-4% (w/w), 4-25%, 25-40% and >40% respectively. However, with an increase in the concentration of hexadecane in PT-water systems, the phase transitioned from Pn3m to H 2 to L 2 without forming the micellar cubic phase.…”

Microfluidics Synthesis of Gene Silencing Cubosomes

“…38 However, because of bulk-scale mixing of ethanol and water, this method also results in high polydispersity of particle sizes. 36,37…”