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, Zoltán Varga, Luc Augis, Guillaume Nugue, Jean Claude Debouzy, Juliette Vergnaud-Gauduchon, Gillian Barratt

Research output: Contribution to journalArticle

2 Scopus citations

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 (US)
Pages (from-to)704-715
Number of pages12
JournalJournal of Colloid And Interface Science
Volume537
DOIs
StatePublished - Mar 1 2019
Externally publishedYes

Keywords

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

PubMed: MeSH publication types

  • Journal Article

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  • Cite this

    Sauvage, F., Legrand, F. X., Roux, M., Rajkovic, I., Weiss, T. M., Varga, Z., Augis, L., Nugue, G., Debouzy, J. C., Vergnaud-Gauduchon, J., & Barratt, G. (2019). Interaction of dequalinium chloride with phosphatidylcholine bilayers: A biophysical study with consequences on the development of lipid-based mitochondrial nanomedicines. Journal of Colloid And Interface Science, 537, 704-715. https://doi.org/10.1016/j.jcis.2018.11.059