Pharmaceutics 2011, 3(3), 379-405; doi:10.3390/pharmaceutics3030379
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

1,2, 2, 2, 2, 2,* email and 1,* email
Received: 4 May 2011; in revised form: 7 June 2011 / Accepted: 30 June 2011 / Published: 11 July 2011
(This article belongs to the Special Issue Colloidal Drug Carrier Systems)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: pH-sensitive liposomes; fliposomes; polyethyleneglycol (PEG); conformational switch; controlled drug release; triggered release
PDF Full-text Download PDF Full-Text [1489 KB, uploaded 11 July 2011 11:20 CEST]

Export to BibTeX |
EndNote


MDPI and ACS Style

Samoshina, N.M.; Liu, X.; Brazdova, B.; Franz, A.H.; Samoshin, V.V.; Guo, X. 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 2011, 3, 379-405.

AMA Style

Samoshina NM, Liu X, Brazdova B, Franz AH, Samoshin VV, Guo X. 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. 2011; 3(3):379-405.

Chicago/Turabian Style

Samoshina, Nataliya M.; Liu, Xin; Brazdova, Barbora; Franz, Andreas H.; Samoshin, Vyacheslav V.; Guo, Xin. 2011. "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 3, no. 3: 379-405.

Pharmaceutics EISSN 1999-4923 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert