title: A two-component micelle with emergent pH responsiveness by mixing dilauroyl phosphocholine and deoxycholic acid and its delivery of proteins into the cytosol.
abstract: Providing appropriate pH responsiveness for drug delivery nanoparticles is one of the major issues in developing a new generation of delivery systems. This paper reports that, when phosphocholine and a bile acid were mixed, the resultant two-component micelle gained pH responsiveness, while the individual components did not show any such responsiveness. The pH responsiveness was shown to be determined by the chemical structure, especially the positions and chirality of the OH groups, of the bile acid, and the sensitivity was determined by the alkyl chain length of the phosphocholine. The best combination for evading endocytosis was dilauroyl phosphocholine (DLPC) and deoxycholic acid (DA). Small-angle X-ray scattering revealed that the pH responsiveness was related to the change of surface hydrophobicity, namely, decreasing pH led to protonation of the carboxylic acid, resulting in aggregation of the preceding micelles. We assume that particles that become hydrophobic in this way can start interacting with the endocytotic bilayer, which eventually leads to rupture of the endocytotic vesicle. This mechanism is well supported by the finding that fluorescein-conjugated ovalbumin proteins were transported into the cytosol when they were co-administered with DLPC/DA.
authors.affiliation: Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyamoto
authors.affiliation: Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Mochizuki
authors.affiliation: Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan. Electronic address: sakurai@kitakyu-u.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sakurai
authors.affiliation: Terumo Corporation R & D Center, 1500, Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sakaguchi
authors.affiliation: Terumo Corporation R & D Center, 1500, Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Koiwai
mesh_terms: D000818:Animals; D001692:Biological Transport; D003600:Cytosol / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D019793:Fluorescein / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D051379:Mice; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D010047:Ovalbumin / Q000737:chemistry / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry*; D000067996:RAW 264.7 Cells; D013194:Staining and Labeling
chemical_list: D008823:Micelles; D010713:Phosphatidylcholines; D003840:Deoxycholic Acid; C015153:1,2-dilauroylphosphatidylcholine; D010047:Ovalbumin; D019793:Fluorescein
keywords: Deoxycholic acid (DA); Dilauroyl phosphocholine (DLPC); Drug delivery system (DDS); Micelle; pH-responsiveness