Tris(2-aminoethyl)amine-based α-branched fatty acid amides - Synthesis of lipids and comparative study of transfection efficiency of their lipid formulations.
The synthesis of a new class of cationic lipids, tris(2-aminoethyl)amine-based α-branched fatty acid amides, is described resulting in a series of lipids with specific variations in the lipophilic as well as the hydrophilic part of the lipids. In-vitro structure/transfection relationships were established by application of complexes of these lipids with plasmid DNA (pDNA) to different cell lines. The α-branched fatty acid amide bearing two tetradecyl chains and two lysine molecules (T14diLys) in mixture with the co-lipid 1,2-di-[(9Z)-octadec-9-enoyl]-sn-glycero-3-phosphoethanolamine (DOPE) (1/2, n/n) exhibits effective pDNA transfer in three different cell lines, namely Hep-G2, A549, and COS-7. The presence of 10% serum during lipoplex incubation of the cells did not affect the transfection efficiency. Based on that, detailed investigations of the complexation of pDNA with the lipid formulation T14diLys/DOPE 1/2 (n/n) were carried out with respect to particle size and charge using dynamic light scattering (DLS), ζ-potential measurements, and transmission electron microscopy (TEM). Additionally, the lipoplex uptake was investigated by confocal laser scanning microscopy (CLSM). Overall, lipoplexes prepared from T14diLys/DOPE 1/2 (n/n) offer large potential as lipid-based polynucleotide carriers and further justify advanced examinations.
Institute of Pharmacy, Biochemical Pharmacy, Martin Luther University (MLU) Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany.
Nicole
N
Erdmann
Institute of Pharmacy, Biochemical Pharmacy, Martin Luther University (MLU) Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany; Department of Pharmaceutical Technology and Biopharmaceutics, Philipps University Marburg, Ketzerbach 63, 35037 Marburg, Germany. Electronic address: christian.woelk@pharmazie.uni-halle.de.
Christian
C
Wölk
Institute of Pharmacy, Biochemical Pharmacy, Martin Luther University (MLU) Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany.
Ingo
I
Schulze
Institute of Pharmacy, Biochemical Pharmacy, Martin Luther University (MLU) Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany.
Christopher
C
Janich
Institute of Pharmacy, Biochemical Pharmacy, Martin Luther University (MLU) Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany.
Manuela
M
Folz
Centre for Innovation Competence - HALOmem, MLU Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle (Saale), Germany.
Simon
S
Drescher
Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
Matthias
M
Dittrich
Martin Luther University Halle-Wittenberg, Center for Structure and Dynamics of Proteins (MZP), Weinbergweg 22, 06120 Halle (Saale), Germany.
Annette
A
Meister
Institute of Pharmacy, Biomedical Materials Group, MLU Halle-Wittenberg, Heinrich-Damerow-Str. 4, 06120 Halle (Saale), Germany.
Jürgen
J
Vogel
Institute of Pharmacy, Biomedical Materials Group, MLU Halle-Wittenberg, Heinrich-Damerow-Str. 4, 06120 Halle (Saale), Germany.
Thomas
T
Groth
Institute of Pharmacy, Biochemical Pharmacy, Martin Luther University (MLU) Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany. Electronic address: bodo.dobner@pharmazie.uni-halle.de.
Bodo
B
Dobner
Institute of Pharmacy, Biochemical Pharmacy, Martin Luther University (MLU) Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany.
Andreas
A
Langner
D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002470:Cell Survival; D002522:Chlorocebus aethiops; D016895:Culture Media, Serum-Free / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism*; D005029:Ethylenediamines / Q000138:chemical synthesis / Q000737:chemistry*; D005227:Fatty Acids / Q000737:chemistry; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D008081:Liposomes; D054878:Lipoylation; D008239:Lysine / Q000031:analogs & derivatives; D015394:Molecular Structure; D009226:Myristates / Q000138:chemical synthesis / Q000737:chemistry; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D013237:Stereoisomerism; D014162:Transfection
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D016895:Culture Media, Serum-Free; D004279:DNA, Viral; D005029:Ethylenediamines; D005227:Fatty Acids; D006020:Glycopeptides; D008081:Liposomes; D009226:Myristates; D010714:Phosphatidylethanolamines; C099539:tris(2-aminoethyl)amine; D008239:Lysine
Cationic lipids; Gene therapy; Lipofection; Lipoplex; Non-viral gene transfer; Synthetic methods