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

JOURNAL OF COLLOID AND INTERFACE SCIENCE

卷:537

Article

Sauvage, Felix¹  Legrand, Francois-Xavier¹  Roux, Michel²  Rajkovic, Ivan³  Weiss, Thomas M.³  Varga, Zoltan⁴  Augis, Luc¹  Nugue, Guillaume⁵  Debouzy, Jean-Claude⁵  Vergnaud-Gauduchon, Juliette¹  Barratt, Gillian¹ 

[1] Univ Paris Saclay, Univ Paris Sud, Inst Galien Paris Sud, CNRS, F-92290 Chatenay Malabry, France

[2] Univ Paris Saclay, Univ Paris Sud, Inst Biol Integrat Cellule, CNRS,CEA, F-91190 Gif Sur Yvette, France

[3] SLAC Natl Accelerator Ctr, Stanford Synchrotron Radiat Lightsource, Menlo Pk, CA 94025 USA

[4] Hungarian Acad Sci, Res Ctr Nat Sci, Inst Mat & Environm Chem, Biol Nanochem Res Grp, Magyar Tudosok Korutja 2, H-1117 Budapest, Hungary

[5] Inst Rech Biomed Armees, Serv Sante Armees, F-91220 Bretigny Sur Orge, France

关键词: Liposomes;    Mitochondria;    Bilayers;    Calorimetry;    X-ray scattering;    NMR spectroscopy;    Drug delivery;    Dequalinium;   

DOI  :  10.1016/j.jcis.2018.11.059

来源: Elsevier

【 摘 要 】

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, P-31 and H-2 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. (C) 2018 Elsevier Inc. All rights reserved.

【 授权许可】

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