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

Journal Article · Thu Nov 15 00:00:00 EST 2018 · Journal of Colloid and Interface Science

DOI:https://doi.org/10.1016/j.jcis.2018.11.059· OSTI ID:1502994

Sauvage, Félix ^[1]; Legrand, François-Xavier ^[1]; Roux, Michel ^[2]; Rajkovic, Ivan ^[3]; Weiss, Thomas M. ^[3]; Varga, Zoltán ^[4]; Augis, Luc ^[1]; Nugue, Guillaume ^[5]; Debouzy, Jean-Claude ^[5]; Vergnaud-Gauduchon, Juliette ^[1]; Barratt, Gillian ^[1]

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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)

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.

• Research Organization: SLAC National Accelerator Lab. (SLAC), Menlo Park, CA (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Basic Energy Sciences (BES)
• Grant/Contract Number: AC02-76SF00515; P41GM103393
• OSTI ID: 1502994
• Alternate ID(s): OSTI ID: 1635952
• Journal Information: Journal of Colloid and Interface Science, Vol. 537, Issue C; ISSN 0021-9797
• Publisher: Elsevier
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
Liposomes
Mitochondria
Bilayers
Calorimetry
X-ray scattering
NMR spectroscopy
Drug delivery
Dequalinium