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Mechanism of formation of DNA-cationic vesicle complexes

Barreleiro, Paula LU ; May, RP and Lindman, Björn LU (2003) In Faraday Discussions 122. p.191-201
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 25degreesC. The results show... (More)
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 25degreesC. 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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Faraday Discussions
volume
122
pages
191 - 201
publisher
Royal Society of Chemistry
external identifiers
  • wos:000178767600014
  • pmid:12555857
  • scopus:0038810192
ISSN
1364-5498
DOI
10.1039/b200796g
language
English
LU publication?
yes
id
412435de-3d9e-4426-942a-8a72d40792b5 (old id 324983)
date added to LUP
2007-08-22 15:28:11
date last changed
2018-05-29 09:18:17
@article{412435de-3d9e-4426-942a-8a72d40792b5,
  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 25degreesC. 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.},
  author       = {Barreleiro, Paula and May, RP and Lindman, Björn},
  issn         = {1364-5498},
  language     = {eng},
  pages        = {191--201},
  publisher    = {Royal Society of Chemistry},
  series       = {Faraday Discussions},
  title        = {Mechanism of formation of DNA-cationic vesicle complexes},
  url          = {http://dx.doi.org/10.1039/b200796g},
  volume       = {122},
  year         = {2003},
}