Structures of malonic acid diamide/phospholipid composites and their lipoplexes.
As a continuation of previous work, the self-assembly process of cationic lipid formulations in the presence and absence of DNA was investigated with respect to binary lipid mixtures suitable as polynucleotide carrier systems. The lipid blends consist of one malonic-acid-based cationic lipid with a varying alkyl chain pattern, either N-{6-amino-1-[N-(9Z)-octadec-9-enylamino]-1-oxohexan-(2S)-2-yl}-N'-{2-[N,N-bis(2-aminoethyl)amino]ethyl}-2-hexadecylpropandiamide () or N-[6-amino-1-oxo-1-(N-tetradecylamino)hexan-(2S)-2-yl]-N'-{2-[N,N-bis(2-aminoethyl)amino]ethyl}-2-hexadecylpropandiamide (), and one neutral co-lipid, either 1,2-di-[(9Z)-octadec-9-enoyl]-sn-glycero-3-phosphocholine (DOPE) or 1,2-di-(hexadecanoyl)-sn-glycero-3-phosphocholine (DPPC). Although the cationic lipids exhibit only slight differences in their structure, the DNA transfer efficiency varies drastically. Therefore, self-assembly was studied in 3D systems by small- and wide-angle X-ray scattering (SAXS and WAXS) and transmission electron microscopy (TEM) as well as in 2D systems by infrared reflection-absorption spectroscopy (IRRAS) on Langmuir films. The investigated lipid mixtures show quite different self-assembly in the absence of DNA, with varying structures from vesicles (/DOPE; /DOPE) and tubes (/DOPE) to discoid structures (/DPPC; /DPPC). Twisted ribbons and sheets, which were stabilized due to hydrogen-bond networks, were found in all investigated lipid mixtures in the absence of DNA. The addition of DNA leads to the formation of lamellar lipoplexes for all the investigated lipid compositions. The lipoplexes differ in crucial parameters, such as the lamellar repeat distance and the spacing between the DNA strands, indicating differences in the binding strength between DNA and the lipid composition. The formation of associates with an ideal charge density might emerge as a key parameter for efficient DNA transfer. Furthermore, the structures observed for the different lipid compositions in the absence of DNA prepare the way for other applications besides gene therapy.
Martin Luther University Halle-Wittenberg, Institute of Pharmacy, Wolfgang-Langenbeck-Strasse 4, 06120 Halle, Saale, Germany. christopher.janich@pharmazie.uni-halle.de christian.woelk@pharmazie.uni-halle.de and Philipps University Marburg, Department of Pharmaceutical Technology and Biopharmacy, Ketzerbach 63, 35037 Marburg, Germany.
Christopher
C
Janich
Max Planck Institute of Colloids and Interfaces, Science Park Potsdam-Golm, Am Mühlenberg 1, 14476 Potsdam, Germany.
Stephanie
S
Taßler
Martin Luther University Halle-Wittenberg, Institute of Chemistry, Physical Chemistry and Institute of Biochemistry and Biotechnology, von-Danckelmann-Platz 4, 06120 Halle, Saale, Germany.
Annette
A
Meister
Martin Luther University Halle-Wittenberg, Biocenter, Weinbergweg 22, 06120 Halle, Saale, Germany.
Gerd
G
Hause
Philipps University Marburg, Department of Pharmaceutical Technology and Biopharmacy, Ketzerbach 63, 35037 Marburg, Germany.
Jens
J
Schäfer
Philipps University Marburg, Department of Pharmaceutical Technology and Biopharmacy, Ketzerbach 63, 35037 Marburg, Germany.
Udo
U
Bakowsky
Max Planck Institute of Colloids and Interfaces, Science Park Potsdam-Golm, Am Mühlenberg 1, 14476 Potsdam, Germany.
Gerald
G
Brezesinski
Martin Luther University Halle-Wittenberg, Institute of Pharmacy, Wolfgang-Langenbeck-Strasse 4, 06120 Halle, Saale, Germany. christopher.janich@pharmazie.uni-halle.de christian.woelk@pharmazie.uni-halle.de.
Christian
C
Wölk
D002412:Cations; D004247:DNA / Q000737:chemistry; D003958:Diamide; D008081:Liposomes; D008314:Malonates / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D012542:Scattering, Radiation; D014162:Transfection; D014961:X-Ray Diffraction
D002412:Cations; D008081:Liposomes; D008314:Malonates; D010743:Phospholipids; D003958:Diamide; D004247:DNA; C008314:malonamide