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

Satya Ranjan Sarker, Satoshi Arai, Motohide Murate, Hiroshi Takahashi, Masaki Takata, Toshihide Kobayashi, Shinji Takeoka

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)364-373
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume422
Issue number1-2
DOIs
Publication statusPublished - 2012 Jan 17

Keywords

  • Cationic lipid
  • Hydrocarbon chain spacer
  • Ionization states
  • Phase transition temperature
  • Transfection efficiency

ASJC Scopus subject areas

  • Pharmaceutical Science

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