Physical-Chemical Investigation of New Cationic Lipids for Gene Transfection

The gene-therapy could be a promising way to cure human diseases like AIDS, cystic fibrosis or cancer. Therefore, cationic lipids were developed as a DNA carrier to create the so-called lipoplexes. The lipoplex should be able to cross the cell membranes and release the DNA near the cell nucleus. The delivery is depended on the structure of these complexes (cationic lipid and negatively charged DNA). For this reason new cationic lipids are permanently synthesized, and their physical-chemical properties have been characterized in 2D (monolayers at the liquid/air interface) and 3D (aqueous dispersions) [1]. To determine the properties of 2D monolayers, we use the pressure/area isotherms, infrared reflection absorption spectroscopy and x-ray methods like GIXD, Reflectivity and TRXF. For experiments in bulk SAXS and WAXS have been used.

The various lipids have a similar basic structure in which the chain pattern differs by the unsaturation degree. Additionally, various head groups with different number of amine groups have been used.

The increasing fluidity (double bonds in the chains) and the increasing size and charge of the head group have an influence on the phase state and the protonation degree of the lipids. We used TRXF to quantify the number of charges per molecule at different pH values. The phase state of the lipid chains has been measured by IRRAS. Furthermore, the adsorption of calf thymus DNA on the lipid monolayers has been quantified by IRRAS depending on the sub phase pH value. The results will be discussed as a function of the chemical structure of the lipids.