title: Fliposomes: pH-controlled release from liposomes containing new trans-2-morpholinocyclohexanol-based amphiphiles that perform a conformational flip and trigger an instant cargo release upon acidification.
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.
authors.affiliation: Department of Chemistry, College of the Pacific, University of the Pacific, Stockton, CA 95211, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Nataliya M
authors.initials: NM
authors.lastname: Samoshina
authors.forename: Vyacheslav A
authors.initials: VA
authors.lastname: Chertkov
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Franz
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Vyacheslav V
authors.initials: VV
authors.lastname: Samoshin
mesh_terms: D003511:Cyclohexanols / Q000737:chemistry*; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D008968:Molecular Conformation; D009025:Morpholines / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D003511:Cyclohexanols; D008081:Liposomes; D009025:Morpholines; D013501:Surface-Active Agents; C572157:trans-2-morpholinocyclohexanol