Fliposomes: pH-controlled release from liposomes containing new trans-2-morpholinocyclohexanol-based amphiphiles that
Yu Zheng1, Xin Liu, Nataliya M Samoshina
1Department of Chemistry, College of the Pacific, University of the Pacific, Stockton, CA 95211, USA.
Abstract:
A new type of pH-sensitive liposome (fliposomes) was designed based on the amphiphiles that are able to perform a pH-triggered conformational flip (flipids). This flip disrupts the liposome membrane and causes rapid release of the liposome cargo, specifically in the areas of increased acidity. The flipids (1-3) are equipped with a trans-2-morpholinocyclohexanol conformational switch, pH-Sensitive fliposomes containing one of these flipids, POPC and PEG-ceramide (molar ratio 50/45/5) were constructed and characterized. These compositions were stable at 4 degrees C and pH 7.4 for several months. Fliposomes loaded with ANTS/DPX demonstrated an unusually quick content release (in a few seconds) at pH below 5.5, which was more efficient in the case of flipid 1 with the shorter linear C12-tails. The pH-titration curve for the fliposome leakage paralleled the curve for the acid-induced conformational flip of 1-3 studied by 1H NMR. A plausible mechanism of the pH-sensitivity starts with an acid-triggered conformational flip of 1, 2 or 3, which changes the molecular size and shape, shortens the lipid tails, and perturbs the liposome membrane resulting in the content leakage.
Related Concept Videos
Modified-Release Drug Delivery Systems: Stimuli-Activated
Modified-Release Drug Delivery Systems: Rate-Programmed II
SNAREs and Membrane Fusion
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
Fusion of Secretory Vesicles with the Plasma Membrane
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
Modified-Release Drug Delivery Systems: Drug Release Characteristics
Membrane Asymmetry Regulating Transporters
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...


