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Divalent Cation Induced DNA-Zwitterionic Vesicle Formulation Compacted for Gene Delivery: Thermodynamic Aspects

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Author(s): Erhan S├╝leymanoglu

Journal: Internet Electronic Journal of Molecular Design
ISSN 1538-6414

Volume: 3;
Issue: 2;
Start page: 93;
Date: 2004;
Original page

Keywords: neutral lipid-DNA self-assemblies | Mg2+ | adiabatic differential scanning calorimetry | phase transitions | non-viral gene delivery

ABSTRACT
Complexes between nucleic acids and phospholipid vesicles have been developed as stable non-viral gene delivery vehicles. Currently employed approach uses positively charged lipid species and a helper zwitterionic lipid, the latter being applied for the stabilization of the whole complex. However, besides problematic steps during their preparation, cationic lipids are toxic for cells. The present work describes some energetic issues pertinent to preparation and use of neutral lipid-DNA self-assemblies, thus avoiding toxicity of lipoplexes. Thermodynamic measurements showed stabilization of polynucleotide helix upon its interaction with liposomes in the presence of divalent metal cations. It is thus possible to suggest this self-assembly as an improved formulation for use in gene delivery. Thermotropic phase transitions of zwitterionic liposomes and their complexes with DNA in the presence of Mg2+ is investigated and compared to the available data for neutral/cationic lipid binary nanocondensates with nucleic acids. Adiabatic differential scanning calorimetric measurements of synthetic phosphatidylcholine vesicles and calf thymus DNA and their ternary complexes with Mg2+ were used to deduce the thermodynamic model describing their structural transitions. The increased DNA-mediated ternary complex thermal stability is achieved by affecting the melting transition temperature of the lipids by nucleic acid induced electrostatic screening of the phospholipid bilayers. Although the pharmacodynamical features of the zwitterionic lipid-Mg2+-DNA nanocondensates remain to be tested in transfection experiments, at least from physicochemical viewpoint, their stability data is encouraging to approach them as a novelDNA-based delivery formulation.
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