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Nucleic Acids Research Advance Access originally published online on December 20, 2006
Nucleic Acids Research 2007 35(3):728-739; doi:10.1093/nar/gkl860
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Nucleic Acids Research, 2007, Vol. 35, No. 3 728-739
© 2006 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Relationships between the physicochemical properties of an amphiphilic triblock copolymers/DNA complexes and their intramuscular transfection efficiency

Mahajoub Bello-Roufaï1,*, Olivier Lambert2 and Bruno Pitard1

1 L'Institut du Thorax, INSERM U533, Faculté de Médecine 44000 Nantes, France 2 IECB-UBS UMR CNRS 5471, Université de Bordeaux 1 33405 Talence, France

*To whom correspondence should be addressed. Tel: +33 2 40 41 29 74; Fax: +33 2 40 41 29 50; Email: bellomb{at}medicine.ufl.edu

Received August 11, 2006. Revised September 25, 2006. Accepted October 3, 2006.

Poly(ethyleneoxide)-poly(propyleneoxide)-poly(ethyleneoxide) triblock copolymer (PEO-PPO-PEO) based plasmid delivery systems are increasingly drawing attention in the field of nonviral gene transfer because of their proven in vivo transfection capability. They result from the simple association of DNA molecules with uncharged polymers. We examined the physicochemical properties of PEO-PPO-PEO/DNA mixtures, in which the PEO-PPO-PEO is Lutrol® (PEO75-PPO30-PEO75), formulated under various conditions. We found that interactions between PEO-PPO-PEO and DNA are mediated by the central hydrophobic block within the block copolymer. Dynamic light scattering and cryo-electron microscopy showed that the mean diameter of transfecting particles as well as their stability depended on the PEO-PPO-PEO/DNA ratio and on the ionic composition of the formulating medium. The most active formulation promoting a good tissue-distribution and an optimal transfection was characterized by a reduced electrophoretic mobility, a mean hydrodynamic diameter of ~250–300 nm and by a conserved B-DNA form as shown by circular dichroism studies. Our study also revealed that the stability of these formulations strongly depended on a concentration balance between the DNA and the PEO-PPO-PEO, over which the DNA conformation was modified, micron-sized particles were generated, and the transgene expression was declined. We showed that the physicochemical properties of PEO-PPO-PEO/DNA formulations directly impact the level of gene expression in transfected muscles.


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