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DNA pre-condensation with an amino acid-based cationic amphiphile. A viable approach for liposome-based gene delivery

Rosa, Monica; Penacho, Nuno; Simoes, Sergio; Lima, Maria C P; Lindman, Björn LU and Miguel, Maria G (2008) In Molecular Membrane Biology 25(1). p.23-34
Abstract
A study related to the development and characterization of a new gene delivery system was performed. The approach consists in both the pre-condensation of plasmid DNA with an arginine-based cationic surfactant, arginine-N-lauroyl amide dihydrochloride (ALA), which was found not to be toxic, and the incorporation of the blood protein transferrin (Tf) into the formulations.Two cationic liposome formulations were used, one composed of a mixture of dioleoyl trimethylammoniopropane and cholesterol (DOTAP:Chol) and the other a pH sensitive formulation constituted of DOTAP, Chol, Dioleoyl phosphatidylethanolamine (DOPE) and cholesteryl hemisuccinate (CHEMS).Particles with different ALA/DNA and cationic lipid/DNA charge ratios were produced and a... (More)
A study related to the development and characterization of a new gene delivery system was performed. The approach consists in both the pre-condensation of plasmid DNA with an arginine-based cationic surfactant, arginine-N-lauroyl amide dihydrochloride (ALA), which was found not to be toxic, and the incorporation of the blood protein transferrin (Tf) into the formulations.Two cationic liposome formulations were used, one composed of a mixture of dioleoyl trimethylammoniopropane and cholesterol (DOTAP:Chol) and the other a pH sensitive formulation constituted of DOTAP, Chol, Dioleoyl phosphatidylethanolamine (DOPE) and cholesteryl hemisuccinate (CHEMS).Particles with different ALA/DNA and cationic lipid/DNA charge ratios were produced and a physicochemical characterization of the systems developed was performed. DNA conformational changes in the presence of ALA were studied by Circular Dichroism (CD) and the ALA binding to DNA was followed by surface tension measurements. Insight into the structure and morphology of the various ALA-complexes (complexes composed of ALA, DNA, Tf and liposomes) was obtained by cryogenic-Transmission Electron Microscopy (cryo-TEM) and the sizes of the ALA-complexes were determined through Photon Correlation Spectroscopy (PCS). We found that the transfection capacity of these systems is directly related with the presence of ALA and the lipidic composition. Complexes based on the pH sensitive liposome formulation present better transfection profiles. The correlation between the inner structure, density and size of the ALA-complexes and their biological activity is discussed. Overall, we demonstrate that the presence of ALA improves the transfection efficiency when conjugated with cationic liposome systems. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cationic liposomes, gene delivery, amino acid-based amphiphile
in
Molecular Membrane Biology
volume
25
issue
1
pages
23 - 34
publisher
Informa Healthcare
external identifiers
  • wos:000252352700003
  • scopus:37549013769
ISSN
0968-7688
DOI
10.1080/09687680701499451
language
English
LU publication?
yes
id
ad364b82-479a-4657-839d-ec945e45edd5 (old id 1199813)
date added to LUP
2008-09-11 11:15:12
date last changed
2017-08-27 04:50:42
@article{ad364b82-479a-4657-839d-ec945e45edd5,
  abstract     = {A study related to the development and characterization of a new gene delivery system was performed. The approach consists in both the pre-condensation of plasmid DNA with an arginine-based cationic surfactant, arginine-N-lauroyl amide dihydrochloride (ALA), which was found not to be toxic, and the incorporation of the blood protein transferrin (Tf) into the formulations.Two cationic liposome formulations were used, one composed of a mixture of dioleoyl trimethylammoniopropane and cholesterol (DOTAP:Chol) and the other a pH sensitive formulation constituted of DOTAP, Chol, Dioleoyl phosphatidylethanolamine (DOPE) and cholesteryl hemisuccinate (CHEMS).Particles with different ALA/DNA and cationic lipid/DNA charge ratios were produced and a physicochemical characterization of the systems developed was performed. DNA conformational changes in the presence of ALA were studied by Circular Dichroism (CD) and the ALA binding to DNA was followed by surface tension measurements. Insight into the structure and morphology of the various ALA-complexes (complexes composed of ALA, DNA, Tf and liposomes) was obtained by cryogenic-Transmission Electron Microscopy (cryo-TEM) and the sizes of the ALA-complexes were determined through Photon Correlation Spectroscopy (PCS). We found that the transfection capacity of these systems is directly related with the presence of ALA and the lipidic composition. Complexes based on the pH sensitive liposome formulation present better transfection profiles. The correlation between the inner structure, density and size of the ALA-complexes and their biological activity is discussed. Overall, we demonstrate that the presence of ALA improves the transfection efficiency when conjugated with cationic liposome systems.},
  author       = {Rosa, Monica and Penacho, Nuno and Simoes, Sergio and Lima, Maria C P and Lindman, Björn and Miguel, Maria G},
  issn         = {0968-7688},
  keyword      = {cationic liposomes,gene delivery,amino acid-based amphiphile},
  language     = {eng},
  number       = {1},
  pages        = {23--34},
  publisher    = {Informa Healthcare},
  series       = {Molecular Membrane Biology},
  title        = {DNA pre-condensation with an amino acid-based cationic amphiphile. A viable approach for liposome-based gene delivery},
  url          = {http://dx.doi.org/10.1080/09687680701499451},
  volume       = {25},
  year         = {2008},
}