Premium
Switchable Lipids: Conformational Change for Fast pH‐Triggered Cytoplasmic Delivery
Author(s) -
Viricel Warren,
Mbarek Amira,
Leblond Jeanne
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201504661
Subject(s) - sulforhodamine b , liposome , chemistry , ethylene glycol , biophysics , cytosol , conformational change , endosome , drug delivery , hela , lipid bilayer , cationic polymerization , peg ratio , biochemistry , membrane , cell , organic chemistry , cytotoxicity , in vitro , finance , economics , biology , enzyme
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.