TY - JOUR
T1 - 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
AU - Sarker, Satya Ranjan
AU - Arai, Satoshi
AU - Murate, Motohide
AU - Takahashi, Hiroshi
AU - Takata, Masaki
AU - Kobayashi, Toshihide
AU - Takeoka, Shinji
PY - 2012/1/17
Y1 - 2012/1/17
N2 - 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.
AB - 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.
KW - Cationic lipid
KW - Hydrocarbon chain spacer
KW - Ionization states
KW - Phase transition temperature
KW - Transfection efficiency
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U2 - 10.1016/j.ijpharm.2011.10.044
DO - 10.1016/j.ijpharm.2011.10.044
M3 - Article
C2 - 22079713
AN - SCOPUS:84655167074
VL - 422
SP - 364
EP - 373
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1-2
ER -