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Article
Fliposomes: pH-sensitive liposomes containing a trans-2-morpholinocyclohexanol-based lipid that performs a conformational flip and triggers an instant cargo release in acidic medium
Pharmaceutics
  • Nataliya M. Samoshina, University of the Pacific
  • Xin Liu, University of the Pacific
  • Barbora Brazdova, University of the Pacific
  • Andreas H. Franz, University of the Pacific
  • Vyacheslav V. Samoshin, University of the Pacific
  • Xin Guo, University of the Pacific
Document Type
Article
Department
Chemistry
DOI
10.3390/pharmaceutics3030379
Publication Date
7-1-2011
Disciplines
Abstract
Incorporation of a pH-sensitive conformational switch into a lipid structure enables a drastic conformational flip upon protonation that disrupts the liposome membrane and causes rapid release of cargo specifically in areas of increased acidity. pH-sensitive liposomes containing the amphiphile (1) with trans-2-morpholinocyclohexanol conformational switch, a phospholipid, and a PEG-lipid conjugate were constructed and characterized. The optimized composition—1/POPC/PEG-ceramide (50/45/5)—could be stored at 4 °C and pH 7.4 for up to 1.5 years, and was stable in blood serum in vitro after 48 h at 37 °C. Liposomes loaded with ANTS/DPX or methotrexate demonstrated an unusually quick content release (in a few seconds) at pH below 5.5, which was independent of inter-liposome contact. The pH-titration curve for the liposome leakage paralleled the curve for the acid-induced conformational flip of 1 studied by 1H-NMR. Freeze-fracture electron microscopy images showed budding and division of the bilayer at pH 5.5. A plausible mechanism of pH-sensitivity involves an acid-triggered conformational flip of 1, shortening of lipid tails, and membrane perturbations, which cause the content leakage. The methotrexate-loaded liposomes demonstrated much higher cytotoxicity in HeLa cells than the free drug indicating that they can serve as viable drug delivery systems.
Creative Commons License
Creative Commons Attribution 4.0
Citation Information
Nataliya M. Samoshina, Xin Liu, Barbora Brazdova, Andreas H. Franz, et al.. "Fliposomes: pH-sensitive liposomes containing a trans-2-morpholinocyclohexanol-based lipid that performs a conformational flip and triggers an instant cargo release in acidic medium" Pharmaceutics Vol. 3 Iss. 3 (2011) p. 379 - 405 ISSN: 1999-4923
Available at: http://works.bepress.com/xin-guo/1/