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

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. As a whole, our work stresses the necessity for thorough physico-chemical characterization to better understand the mechanisms underlying the development of nanomedicines.

Authors:
 [1];  [1];  [2];  [3];  [3];  [4];  [1];  [5];  [5];  [1];  [1]
  1. Paris-Sud Univ., Châtenay-Malabry (France)
  2. Paris-Sud Univ., Gif-Sur-Yvette (France)
  3. SLAC National Accelerator Lab. (SLAC), Menlo Park, CA (United States)
  4. Hungarian Academy of Sciences, Budapest (Hungary)
  5. Institut de Recherche Biomédicale des Armées (IRBA), Brétigny-sur-Orge (France)
Publication Date:
Research Org.:
SLAC National Accelerator Lab. (SLAC), Menlo Park, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1502994
Grant/Contract Number:  
AC02-76SF00515; P41GM103393
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Journal of Colloid and Interface Science
Additional Journal Information:
Journal Volume: 537; Journal Issue: C; Journal ID: ISSN 0021-9797
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; Liposomes; Mitochondria; Bilayers; Calorimetry; X-ray scattering; NMR spectroscopy; Drug delivery; Dequalinium

Citation Formats

Sauvage, Félix, Legrand, François-Xavier, Roux, Michel, Rajkovic, Ivan, Weiss, Thomas M., Varga, Zoltán, Augis, Luc, Nugue, Guillaume, Debouzy, Jean-Claude, Vergnaud-Gauduchon, Juliette, and Barratt, Gillian. Interaction of dequalinium chloride with phosphatidylcholine bilayers: A biophysical study with consequences on the development of lipid-based mitochondrial nanomedicines. United States: N. p., 2018. Web. doi:10.1016/j.jcis.2018.11.059.
Sauvage, Félix, Legrand, François-Xavier, Roux, Michel, Rajkovic, Ivan, Weiss, Thomas M., Varga, Zoltán, 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. United States. doi:10.1016/j.jcis.2018.11.059.
Sauvage, Félix, Legrand, François-Xavier, Roux, Michel, Rajkovic, Ivan, Weiss, Thomas M., Varga, Zoltán, Augis, Luc, Nugue, Guillaume, Debouzy, Jean-Claude, Vergnaud-Gauduchon, Juliette, and Barratt, Gillian. Thu . "Interaction of dequalinium chloride with phosphatidylcholine bilayers: A biophysical study with consequences on the development of lipid-based mitochondrial nanomedicines". United States. doi:10.1016/j.jcis.2018.11.059.
@article{osti_1502994,
title = {Interaction of dequalinium chloride with phosphatidylcholine bilayers: A biophysical study with consequences on the development of lipid-based mitochondrial nanomedicines},
author = {Sauvage, Félix and Legrand, François-Xavier and Roux, Michel and Rajkovic, Ivan and Weiss, Thomas M. and Varga, Zoltán and Augis, Luc and Nugue, Guillaume and Debouzy, Jean-Claude and Vergnaud-Gauduchon, Juliette and Barratt, Gillian},
abstractNote = {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. As a whole, our work stresses the necessity for thorough physico-chemical characterization to better understand the mechanisms underlying the development of nanomedicines.},
doi = {10.1016/j.jcis.2018.11.059},
journal = {Journal of Colloid and Interface Science},
issn = {0021-9797},
number = C,
volume = 537,
place = {United States},
year = {2018},
month = {11}
}

Journal Article:
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This content will become publicly available on November 15, 2019
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