title: Investigation of Binary Lipid Mixtures of a Three-Chain Cationic Lipid with Phospholipids Suitable for Gene Delivery.
abstract: In the present work, we characterize binary lipid mixtures consisting of a three-chain amino-functionalized cationic lipid (DiTT4) with different phospholipids, namely, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE), or 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). The mixing behavior was investigated by differential scanning calorimetry (DSC). Additionally, aqueous dispersions of the binary mixtures were characterized by means of dynamic light scattering (DLS), laser Doppler electrophoresis, and transmission electron microscopy (TEM) to get further information about particle size, charge, and shape. The complex formation between different binary lipid mixtures and plasmid DNA (pDNA) was investigated by zeta-(ζ)-potential (laser Doppler electrophoresis) and DLS measurements, and the lipid/DNA complexes (lipoplexes) were screened for efficient DNA transfer (transfection) in cell culture. Finally, efficient lipid compositions were investigated with respect to serum stability. This work provides a detailed characterization of the cationic lipid mixtures as foundation for further research. Efficient gene transfer in the presence of serum was demonstrated for selected lipoplexes showing their capability to be used as high-potency gene delivery vehicles.
authors.affiliation: Philipps University Marburg , Department of Pharmaceutical Technology and Biopharmaceutics, Ketzerbach 63, 35037 Marburg, Germany.|Martin Luther University (MLU) Halle-Wittenberg , Institute of Pharmacy, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Wölk
authors.affiliation: Martin Luther University (MLU) Halle-Wittenberg , Institute of Pharmacy, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Janich
authors.affiliation: MLU Halle-Wittenberg , Center for Structure and Dynamics of Proteins (MZP), Weinbergweg 22, 06120 Halle (Saale), Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Meister
authors.affiliation: Martin Luther University (MLU) Halle-Wittenberg , Institute of Pharmacy, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Drescher
authors.affiliation: Martin Luther University (MLU) Halle-Wittenberg , Institute of Pharmacy, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Langner
authors.affiliation: Max Planck Institute of Colloids and Interfaces , Science Park Potsdam-Golm, Am Mühlenberg 1, 14476 Potsdam, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Brezesinski
authors.affiliation: Philipps University Marburg , Department of Pharmaceutical Technology and Biopharmaceutics, Ketzerbach 63, 35037 Marburg, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Bakowsky
mesh_terms: D002412:Cations / Q000737:chemistry; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D014162:Transfection
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002412:Cations; D010714:Phosphatidylethanolamines; D004247:DNA; D004134:Dimyristoylphosphatidylcholine; C018525:1,2-dimyristoylphosphatidylethanolamine