title: Temperature and pH sensitivity of a stabilized self-nanoemulsion formed using an ionizable lipid-like material via an oil-to-surfactant transition.
abstract: Lipids functionalized with tertiary amines (ionizable lipids) for a pH-dependent positive charge have been developed extensively as a carrier material for delivering nucleic acids. We previously developed an SS-cleavable proton-activated lipid-like material (ssPalm) as a component of a functionalized lipid envelope structure of a nanoparticle that encapsulated plasmid DNA and short interfering RNA. In this study, we report on the unique characteristics of such an ionizable lipid: the formation of a nano-sized emulsion (ave. 40nm) via pH-triggered self-emulsification in the absence of a cargo (nucleic acids). The particle has a neutral charge at physiological pH and is stabilized by helper lipids and polyethyleneglycol (PEG)-conjugated lipids. The generalized polarization of 6-dodecanoyl-2-dimethylaminonaphthalene (Laurdan), which indicates the surface polarity caused by the invasion of water onto the surface, changes dynamically in response to pH and temperature, while the fluidity of the intra-particle compartment, as measured by the fluorescence anisotropy of 1,6-Diphenyl-1,3,5-hexatriene (DPH), is not affected. Even when the particle contains a high density of PEG on the surface, it shows a high fusogenecity to negatively charged liposomes in response to an acidic pH to a higher degree than a conventional cationic lipid. These characteristics suggest that the ssPalm particle possesses unique properties for delivering lipophilic drugs across the biomembrane.
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Sapporo City, Hokkaido 060-0812, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Laboratory of Molecular Cell Dynamics, Faculty of Advanced Life Science, Hokkaido University, Kita 21 Nishi 11, Sapporo City, Hokkaido 001-0021, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Oasa
authors.affiliation: Laboratory of Molecular Cell Dynamics, Faculty of Advanced Life Science, Hokkaido University, Kita 21 Nishi 11, Sapporo City, Hokkaido 001-0021, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Kinjo
authors.affiliation: NOF CORPORATION, 3-3 Chidori-cho, Kawasaki-ku, Kawasaki city, Kanagawa 210-0865, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Tange
authors.affiliation: NOF CORPORATION, 3-3 Chidori-cho, Kawasaki-ku, Kawasaki city, Kanagawa 210-0865, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Nakai
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Sapporo City, Hokkaido 060-0812, Japan.
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Sapporo City, Hokkaido 060-0812, Japan; Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba City, Chiba 260-0875, Japan. Electronic address: akitahide@chiba-u.jp.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Akita
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives* / Q000737:chemistry; D016880:Anisotropy; D004161:Diphenylhexatriene / Q000737:chemistry; D004655:Emulsions; D000431:Ethanol / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007848:Laurates / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry; D009696:Nucleic Acids / Q000737:chemistry; D009821:Oils; D010316:Particle Size; D010957:Plasmids / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D012995:Solubility; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry*; D013696:Temperature; D014867:Water / Q000737:chemistry
chemical_list: D004655:Emulsions; D007848:Laurates; D008055:Lipids; D008081:Liposomes; D009696:Nucleic Acids; D009821:Oils; D034741:RNA, Small Interfering; D013501:Surface-Active Agents; D014867:Water; D004161:Diphenylhexatriene; D000431:Ethanol; D011092:Polyethylene Glycols; D015081:2-Naphthylamine; C065580:laurdan
keywords: Biodegradable materials; Colloids; Emulsions; Fluorescence; Nanoparticles