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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. February 2004, Volume 3, Number 2, 93-101 |
Divalent Cation Induced DNA-Zwitterionic Vesicle Formulation Compacted
for Gene Delivery: Thermodynamic Aspects
Erhan Süleymanoglu
Internet Electron. J. Mol. Des. 2004, 3, 93-101
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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 novel
DNA-based delivery formulation.
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