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

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 (TM) 2000. We synthesized a series of amino acid-based cationic lipids with different ionization states (i.e., -NH2, -NH3+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 -NH3+Cl- and a vesicular structure both in the presence of -NH2 and -NH(3)(+)TFA(-). Differential scanning calorimetry (DSC) data revealed a significantly lower (8.1 degrees C) gel -to-liquid crystalline phase transition temperature for cationic assemblies bearing -NH(3)(+)TFA(-) when compared to their -NH2 counterparts. Furthermore, the zeta potential of cationic assemblies having -NH3+ TFA(-) in the hydrophilic head group was maximum followed by -NH3+Cl- and -NH2 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(-) > -NH3+ Cl- > -NH2. (c) 2011 Elsevier B.V. All rights reserved.