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Volume 122, 2003
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Mechanism of formation of DNA–cationic vesicle complexes

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Abstract

Cationic vesicles and DNA form complexes that are promising gene delivery systems. Despite the increasing number of publications on their morphology and structure, the mechanism leading to their formation is not yet understood due to a lack of kinetic data. In the present study the kinetics of the interaction between DNA and cationic vesicles were followed using stopped-flow turbidity and small-angle neutron scattering techniques. The neutron real-time experiments were performed on a high-flux diffractometer, the D22 at the ILL, using a stopped-flow set-up. Extruded mixed vesicles of dimethyldioctadecylammonium bromide (DODAB) with various amounts of dioleoylphosphatidylethanolamine (DOPE) were investigated at 25 °C. The results show that the transition from unilamellar vesicles to a multilamellar structure upon DNA addition occurs in three steps. The first step, on the millisecond time scale, is currently not accessible to neutron scattering but was observed by stopped-flow turbidity and fluorescence experiments. The second step, on a time scale of seconds, corresponds to the formation of an intermediate with a locally cylindrical structure. As time progresses this unstable intermediate evolves to a multilamellar structure, on a time scale of minutes. An understanding of the mechanisms behind the DNA–cationic vesicle complex formation event will allow the production of more homogeneous, efficient delivery systems in pharmaceutically acceptable forms.

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Publication details

The article was received on 24 Jan 2002, accepted on 08 Mar 2002 and first published on 05 Aug 2002


Article type: Paper
DOI: 10.1039/B200796G
Faraday Discuss., 2003,122, 191-201

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    Mechanism of formation of DNA–cationic vesicle complexes

    P. C. A. Barreleiro, R. P. May and B. Lindman, Faraday Discuss., 2003, 122, 191
    DOI: 10.1039/B200796G

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