title: Evaluation of the influence of ionization states and spacers in the thermotropic phase behaviour of amino acid-based cationic lipids and the transfection efficiency of their assemblies.
abstract: The influence of both the ionization states and the hydrocarbon chain spacer of a series of amino acid-based cationic lipids was evaluated in terms of gene delivery efficiency and cytotoxicity to the COS-7 cell line and compared with that of Lipofectamine 2000. We synthesized a series of amino acid-based cationic lipids with different ionization states (i.e., -NH(2), -NH(3)(+)Cl(-) or -NH(3)(+)TFA(-)) in the lysine head group and different hydrocarbon chain spacers (i.e., 0, 3, 5 or 7 carbon atoms) between the hydrophilic head group and hydrophobic moieties. In the 3-carbon series, the cationic assemblies formed a micellar structure in the presence of -NH(3)(+)Cl(-) and a vesicular structure both in the presence of -NH(2) and -NH(3)(+)TFA(-). Differential scanning calorimetry (DSC) data revealed a significantly lower (8.1°C) gel-to-liquid crystalline phase transition temperature for cationic assemblies bearing -NH(3)(+)TFA(-) when compared to their -NH(2) counterparts. Furthermore, the zeta potential of cationic assemblies having -NH(3)(+)TFA(-) in the hydrophilic head group was maximum followed by -NH(3)(+)Cl(-) and -NH(2) irrespective of their hydrocarbon chain spacer length. The gene delivery efficiency in relation to the ionization states of the hydrophilic head group was as follows: -NH(3)(+)TFA(-)>-NH(3)(+)Cl(-)>-NH(2).
authors.affiliation: Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University (TWIns), Shinjuku-ku, Tokyo 162-8480, Japan.
authors.forename: Satya Ranjan
authors.initials: SR
authors.lastname: Sarker
authors.forename: Satoshi
authors.initials: S
authors.lastname: Arai
authors.forename: Motohide
authors.initials: M
authors.lastname: Murate
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masaki
authors.initials: M
authors.lastname: Takata
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Takeoka
mesh_terms: D000643:Ammonium Chloride / Q000737:chemistry; D000818:Animals; D019556:COS Cells; D002152:Calorimetry, Differential Scanning; D002412:Cations; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D017930:Genes, Reporter; D006838:Hydrocarbons / Q000737:chemistry* / Q000633:toxicity; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry* / Q000633:toxicity; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008239:Lysine / Q000737:chemistry* / Q000633:toxicity; D008823:Micelles; D015394:Molecular Structure; D044367:Phase Transition; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection / Q000379:methods*; D044366:Transition Temperature
chemical_list: D002412:Cations; D006838:Hydrocarbons; D008055:Lipids; C086724:Lipofectamine; D008823:Micelles; D000643:Ammonium Chloride; D008156:Luciferases; D008239:Lysine