Fliposomes: new amphiphiles based on trans-3,4-bis(acyloxy)-piperidine able to perform a pH-triggered conformational flip and cause an instant cargo release from liposomes

Fliposomes: stimuli-triggered conformational flip of novel amphiphiles causes an instant cargo release from liposomes

“…Our liposome design is based on a drastic conformational flip performed simultaneously by a significant part of these structurally simple and synthetically accessible pH-sensitive molecules upon protonation. In our studies, the pHresponsive amphiphiles constituted from 25% to 90% (in most experiments, 50 mol%) of the whole lipid composition (36)(37)(38)(39)(40)(41)(42). This massive uprising disturbs the liposome membrane instantaneously and induces a rapid release of the liposome payload specifically in response to increased acidity of the medium.…”

“…We recently suggested a novel strategy to render liposomes pH sensitive: a protonation-induced conformational switch of hydrocarbon chains in latent amphiphiles composing the liposome membrane (30,(36)(37)(38)(39)(40)(41)(42). Our liposome design is based on a drastic conformational flip performed simultaneously by a significant part of these structurally simple and synthetically accessible pH-sensitive molecules upon protonation.…”

“…To highlight the key role of the conformational flip in pH-triggered liposome leakage, we introduced the terms 'flipids' for amphiphiles equipped with a pH-sensitive conformational switch and 'fliposomes' for liposomes composed of this material (30,(36)(37)(38)(39)(40)(41)(42). This should not be confused with a lipid translocation (flip-flop) that was involved in many reported lipid phase changes (43)(44)(45)(46).…”

“…The compatibility of the pH-sensitive conformational trigger with commonly used lipids, ability to control the rate and extent of liposome content release, mechanism of lipid membrane destabilization, and viability of fliposomes for drug delivery have been studied (36)(37)(38)(39)(40)(41)(42). Of special interest was the ability of flipids to trigger the PEGylated liposomes due to their prolonged life in blood circulation and successful applications in drug/gene delivery (2,4,5,10,14,34).…”

Liposomes in tissue engineering and regenerative medicine

“…In vitro and in vivo studies have shown that the main interactions of liposomes with cells are simple adsorption (by specific interactions with cell-surface components, electrostatic forces, or by non-specific weak hydrophobic forces) or following endocytosis [37]. Many attempts to activate the release of bioactive agents from liposomes in the vicinity of or inside the cells have been described [17,97]. Active release relies on developing mechanisms to increase the permeability or to destabilize the liposome bilayer once it reaches the target site.…”