Surface Recognition and Complexations Between Synthetic Poly(ribo)nucleotides and Neutral Phospholipids and Their Implications in Lipofection

Erhan Soleymanoglu

doi:10.22037/ijpr.2010.648

IJ Pharmaceutical Research

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https://doi.org/10.22037/ijpr.2010.648

Surface Recognition and Complexations Between Synthetic Poly(ribo)nucleotides and Neutral Phospholipids and Their Implications in Lipofection

Author(s):

Erhan Soleymanoglu^{1, 2,*}

1The Slovak Academy of Sciences, Institute of Experimental Physics, Department of Biophysics, Košice, The Slovak Republic

2Biophysics and Microscopy Group, Section of Molecular Cytology, Institute for Molecular Cell Biology, BioCentrum Amsterdam, University of Amsterdam, Amsterdam, The Netherlands

IJ Pharmaceutical Research:Vol. 5, issue 1; 17-29

Published online:Nov 20, 2010

Article type:Research Article

Received:Apr 21, 2004

Accepted:Jul 21, 2005

How to Cite:Erhan SoleymanogluSurface Recognition and Complexations Between Synthetic Poly(ribo)nucleotides and Neutral Phospholipids and Their Implications in Lipofection.Iran J Pharm Res.5(1):e128258.https://doi.org/10.22037/ijpr.2010.648.

Abstract

Thermodynamic features related to preparation and use of self-assemblies formed between multilamellar and unilamellar zwitterionic liposomes and polynucleotides with various conformation and sizes are presented. The divalent metal cation or surfactant-induced adsorption, aggregation and adhesion between single- and double-stranded polyribonucleotides and phosphatidylcholine vesicles was followed by differential adiabatic scanning microcalorimetry. Nucleic acid condensation and compaction mediated by Mg²⁺ and N-alkyl-N,N,N-trimetylammonium ions (CnTMA, n=12), regarding to interfacial interaction with unilamellar vesicles. Microcalorimetric measurements of synthetic phospholipid vesicles and poly(ribo)nucleotides and their ternary complexes with inorganic cations were used to build the thermodynamic model of their structural transitions. The increased thermal stability of the phospholipid bilayers is achieved by affecting their melting transition temperature by nucleic acid induced electrostatic charge screening. Measurements give evidence for the stabilization of polynucleotide helices upon their association with liposomes in the presence of divalent metal cations. Such an induced aggregation of vesicles either leads to heterogeneous multilamellar DNA-lipid arrangements, or to DNA-induced bilayer destabilization and lipid fusion. In contrast, stable monodispersed complexes are formed after compaction of DNA with surfactant, followed by the addition of vesicles. Surfactants bind to DNA in a cooperative manner and increased number of nucleic acid-bound C₁₂TMA leads to a rise in the size of the resulting DNA-surfactant complexes, due to their aggregation. The formation of these bundles is governed by both elctrostatic and hydrophobic interactions of surfactant chains, the reaction being mediated by condensed counterions, steric hindrance or by intrinsic chain flexibility. In here, further employment of these polyelectrolyte nanostructures as an improved formulation in therapeutic gene delivery trials, as well as in DNA chromatography is discussed.

Keywords

Polyelectrolyte phospholipid-polynucleotide nanostructures

Differential scanning microcalorimetry

Phase behaviour

Non-viral gene delivery

DNA chromatography

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Author(s):

Erhan Soleymanoglu:[PubMed][Scholar]