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Contents release from redox-responsive liposomes is anion-specific. Liposomal contents release is initiated by the contact of apposed liposome bilayers having in their outer leaflet 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), whose presence is due to the redox-stimulated removal of a quinone propionic acid protecting group (Q) from Q-DOPE lipids. Contents release occurs upon the phase transition of DOPE from its lamellar liquid-crystalline phase (Lα) to its hexagonal-II inverted micelle (HII) phase. Contents release is slower in the presence of weakly hydrated chaotropic anions versus highly hydrated kosmotropic anions and is attributed to ion accumulation near the zwitterionic DOPE headgroups, in turn altering the headgroup hydration, as indicated by the Lα → HII phase transition temperature, TH, for DOPE. The results are significant, not only for mechanistic aspects of liposome contents release in DOPE-based systems but also for drug delivery applications wherein exist at drug targeting sites variations in the type and concentration of ions and neutral species.

Release Rates of Liposomal Contents Are Controlled by Kosmotropes and Chaotropes