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
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) w...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2011-07-01
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| Series: | Pharmaceutics |
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| Online Access: | http://www.mdpi.com/1999-4923/3/3/379/ |
| _version_ | 1828119856361242624 |
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| author | Barbora Brazdova Andreas H. Franz Vyacheslav V. Samoshin Xin Guo Xin Liu Nataliya M. Samoshina |
| author_facet | Barbora Brazdova Andreas H. Franz Vyacheslav V. Samoshin Xin Guo Xin Liu Nataliya M. Samoshina |
| author_sort | Barbora Brazdova |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T13:54:50Z |
| format | Article |
| id | doaj.art-4ec9019172cc4160a67f971f6d009779 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T13:54:50Z |
| publishDate | 2011-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-4ec9019172cc4160a67f971f6d0097792022-12-22T04:20:22ZengMDPI AGPharmaceutics1999-49232011-07-013337940510.3390/pharmaceutics3030379Fliposomes: pH-Sensitive Liposomes Containing a trans-2-morpholinocyclohexanol-Based Lipid That Performs a Conformational Flip and Triggers an Instant Cargo Release in Acidic MediumBarbora BrazdovaAndreas H. FranzVyacheslav V. SamoshinXin GuoXin LiuNataliya M. SamoshinaIncorporation 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.http://www.mdpi.com/1999-4923/3/3/379/pH-sensitive liposomesfliposomespolyethyleneglycol (PEG)conformational switchcontrolled drug releasetriggered release |
| spellingShingle | Barbora Brazdova Andreas H. Franz Vyacheslav V. Samoshin Xin Guo Xin Liu Nataliya M. Samoshina 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 pH-sensitive liposomes fliposomes polyethyleneglycol (PEG) conformational switch controlled drug release triggered release |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | pH-sensitive liposomes fliposomes polyethyleneglycol (PEG) conformational switch controlled drug release triggered release |
| url | http://www.mdpi.com/1999-4923/3/3/379/ |
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