title: Switchable Lipids: Conformational Change for Fast pH-Triggered Cytoplasmic Delivery.
abstract: We report the use of switchable lipids to improve the endosomal escape and cytosolic delivery of cell-impermeable compounds. The system is based on a conformational reorganization of the lipid structure upon acidification, as demonstrated by NMR spectroscopic studies. When incorporated in a liposome formulation, the switchable lipids triggered bilayer destabilization through fusion even in the presence of poly(ethylene glycol). We observed 88 % release of sulforhodamine B in 15 min at pH 5, and the liposome formulations demonstrated high stability at pH 7.4 for several months. By using sulforhodamine B as a model of a highly polar drug, we demonstrated fast cytosolic delivery mediated by endosomal escape in HeLa cells, and no toxicity.
authors.affiliation: Faculty of Pharmacy, University of Montreal, P.O. Box 6128, Downtown Station, Montreal, Quebec (Canada).
authors.forename: Warren
authors.initials: W
authors.lastname: Viricel
authors.affiliation: Faculty of Pharmacy, University of Montreal, P.O. Box 6128, Downtown Station, Montreal, Quebec (Canada).
authors.forename: Amira
authors.initials: A
authors.lastname: Mbarek
authors.affiliation: Faculty of Pharmacy, University of Montreal, P.O. Box 6128, Downtown Station, Montreal, Quebec (Canada). jeanne.leblond-chain@umontreal.ca.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Leblond
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D065546:Drug Liberation; D011992:Endosomes / Q000378:metabolism; D005456:Fluorescent Dyes / Q000008:administration & dosage*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008561:Membrane Fusion; D008968:Molecular Conformation; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D012235:Rhodamines / Q000008:administration & dosage*
chemical_list: D003692:Delayed-Action Preparations; D005456:Fluorescent Dyes; D008055:Lipids; D008081:Liposomes; D012235:Rhodamines; C022027:lissamine rhodamine B; D011092:Polyethylene Glycols
keywords: conformational change; drug delivery; endosomal escape; liposomes; pH responsiveness