title: 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.
authors: Amorepacific Corporation R&D Center , Yonggu-daero, Yongin, 446-729, South Korea.
authors: Do-Hoon
authors: DH
authors: Kim
authors: Department of Chemical Engineering, Hanyang University , Seoul, 133-791, South Korea.
authors: Sora
authors: S
authors: Lim
authors: Amorepacific Corporation R&D Center , Yonggu-daero, Yongin, 446-729, South Korea.
authors: Jongwon
authors: J
authors: Shim
authors: Department of Chemical Engineering, Hanyang University , Seoul, 133-791, South Korea.
authors: Ji Eun
authors: JE
authors: Song
authors: Department of Agricultural Science, Korea National Open University , Seoul, 110-791, South Korea.
authors: Jong Soo
authors: JS
authors: Chang
authors: Pohang Accelerator Laboratory, Pohang University of Science and Technology , 80 Jigokro-127-beongil, Pohang, 790-784, Korea.
authors: Kyeong Sik
authors: KS
authors: Jin
authors: Department of Chemical Engineering, Hanyang University , Seoul, 133-791, South Korea.
authors: Eun Chul
authors: EC
authors: Cho
mesh_terms: D005233:Fatty Alcohols / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D050866:Liquid Crystals / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry; D053838:Scattering, Small Angle; D013696:Temperature; D014810:Vitamin E / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D005233:Fatty Alcohols; D008055:Lipids; D020442:Poloxamer; D014810:Vitamin E; C508873:3,7,11,15-tetramethyl-1,2,3-hexadecanetriol
keywords: evaporation method; internal structures; large scale synthesis; lipid crystalline lipid nanoparticles; vesicles to lipid-filled nanoparticle transitions