Interaction of dequalinium chloride with phosphatidylcholine bilayers: A biophysical study with consequences on the development of lipid-based mitochondrial nanomedicines

Félix Sauvage, François Xavier Legrand, Michel Roux, Ivan Rajkovic, Thomas M. Weiss, Z. Varga, Luc Augis, Guillaume Nugue, Jean Claude Debouzy, Juliette Vergnaud-Gauduchon, Gillian Barratt

Research output: Contribution to journalArticle

Abstract

Dequalinium (DQ) has been proposed as a mitochondrial targeting ligand for nanomedicines, including liposomes, given the implication of these organelles in many diseases. This original study focuses on the interactions of DQ with phosphatidylcholine bilayers during the formation of liposomes. Firstly, PEGylated liposomes suitable for drug delivery were studied and were found to be more stable when made in water than in phosphate-buffered saline, emphasizing the role of electrostatic interactions between positive charges on DQ and the polar head groups of the lipids. To gain more information, differential scanning calorimetry, small- and wide-angle X-ray scattering and diffraction, 31P and 2H NMR spectroscopy and freeze-fracture electron microscopy were performed on dimyristoylphosphatidylcholine (DMPC) model membranes in the presence of DQ. This molecule was shown to be located at the level of polar head groups and to induce electrostatic repulsions between adjacent lipid bilayers leading to membrane budding in water. These findings indicate that DQ is not completely inert towards lipid membranes and therefore is not an ideal candidate for encapsulation in liposomes. Overall, our work stresses the necessity for thorough physico-chemical characterization to better understand the mechanisms underlying the development of nanomedicines.

Original languageEnglish
Pages (from-to)704-715
Number of pages12
JournalJournal of Colloid And Interface Science
Volume537
DOIs
Publication statusPublished - Mar 1 2019

Fingerprint

Dequalinium
Medical nanotechnology
Liposomes
Phosphatidylcholines
Lipids
Membranes
Lipid bilayers
Dimyristoylphosphatidylcholine
Coulomb interactions
X ray scattering
Drug delivery
Encapsulation
Water
Electron microscopy
Nuclear magnetic resonance spectroscopy
Differential scanning calorimetry
Electrostatics
Membrane Lipids
Phosphates
Ligands

Keywords

  • Bilayers
  • Calorimetry
  • Dequalinium
  • Drug delivery
  • Liposomes
  • Mitochondria
  • NMR spectroscopy
  • X-ray scattering

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Surfaces, Coatings and Films
  • Colloid and Surface Chemistry

Cite this

Interaction of dequalinium chloride with phosphatidylcholine bilayers : A biophysical study with consequences on the development of lipid-based mitochondrial nanomedicines. / Sauvage, Félix; Legrand, François Xavier; Roux, Michel; Rajkovic, Ivan; Weiss, Thomas M.; Varga, Z.; Augis, Luc; Nugue, Guillaume; Debouzy, Jean Claude; Vergnaud-Gauduchon, Juliette; Barratt, Gillian.

In: Journal of Colloid And Interface Science, Vol. 537, 01.03.2019, p. 704-715.

Research output: Contribution to journalArticle

Sauvage, Félix ; Legrand, François Xavier ; Roux, Michel ; Rajkovic, Ivan ; Weiss, Thomas M. ; Varga, Z. ; Augis, Luc ; Nugue, Guillaume ; Debouzy, Jean Claude ; Vergnaud-Gauduchon, Juliette ; Barratt, Gillian. / Interaction of dequalinium chloride with phosphatidylcholine bilayers : A biophysical study with consequences on the development of lipid-based mitochondrial nanomedicines. In: Journal of Colloid And Interface Science. 2019 ; Vol. 537. pp. 704-715.
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