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
N1 - Funding Information:
Authors would like to thank Peter Greimel, Takuma Kishimoto, Nario Tomishige, Takaaki Hikima, RIKEN Spring-8 Centre, Harima, Japan, for performing Small Angle X-ray Scattering (SAXS) analysis of cationic lipid. Authors would also like to thank Dr. Keitaro Sou, Waseda University, for valuable discussion regarding data analysis and manuscript preparation. This work was partially supported by the GCOE “Practical chemical wisdom” and “High-Tech Research Centre” project for Waseda University: matching fund subsidy from MEXT, Japan .
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 -