title: Effect of hydrophobic scaffold on the cellular uptake and gene transfection activities of DNA-encapsulating liposomal nanoparticles via intracerebroventricular administration.
abstract: Efficient DNA carriers are needed as a gene medication for curing brain disorders. In the present study, the function of a neutral lipid envelope-type nanoparticle (LNP) encapsulating pDNA was evaluated after intracerebroventricular administration. The lipid envelope was composed of a series of SS-cleavable and pH-activated lipid like materials (ssPalm) including myristic acid, vitamin A and vitamin E in the hydrophobic scaffold (LNPssPalmM, LNPssPalmA, LNPssPalmE, respectively). The LNPssPalmA and LNPssPalmE were extensively distributed in the corpus callosum, and then gene expression occurred mainly astrocytes in this region, while not in LNPssPalmM. The recombinant human ApoE3-dependent enhancement of the uptake into an astrocyte-derived cell line (KT-5) was observed in LNPssPalmA and LNPssPalmE. Thus, ApoE in the brain plays a key role in the cellular uptake of these particles by astrocytes, and this uptake is dependent on the structure of the hydrophobic scaffold.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan. Electronic address: akita@pharm.hokudai.ac.jp.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Akita
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Nakatani
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kuroki
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Maenaka
authors.affiliation: NOF CORPORATION, 3-3Chidori-cho, Kawasaki-ku, Kawasaki, Kanagawa 210-0865, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Tange
authors.affiliation: NOF CORPORATION, 3-3Chidori-cho, Kawasaki-ku, Kawasaki, Kanagawa 210-0865, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Nakai
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan. Electronic address: harasima@pharm.hokudai.ac.jp.
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D001057:Apolipoproteins E / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D057967:Infusions, Intraventricular; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D014162:Transfection / Q000379:methods; D014801:Vitamin A / Q000737:chemistry; D014810:Vitamin E / Q000737:chemistry
chemical_list: D001057:Apolipoproteins E; D008055:Lipids; D008081:Liposomes; D014801:Vitamin A; D014810:Vitamin E; D004247:DNA
keywords: Brain; DNA delivery; Lipid; Nanoparticles