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Novel pH-sensitive paramagnetic liposomes with improved MR properties.

Knut-Egil Løkling·Roald Skurtveit·Atle Bjørnerud·Sigrid L Fossheim
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Abstract

The use of paramagnetic pH-sensitive liposomes was recently suggested as a new approach for monitoring pathologic changes in pH by MRI. Such liposomes must be stable in blood and selectively release the encapsulated paramagnetic agent when exposed to lower pH in the target tissue. In the present study, different liposomal systems were formulated and characterized by relaxometry, cryo-transmission electron microscopy (cryo-TEM), and MRI. The pH-sensitive system dipalmitoylphosphatidylethanolamine/palmitic acid (DPPE/PA) liposomal GdDTPA-BMA, which was previously shown to be unstable in blood, was modified to improve its stability. The incorporation of cholesterol into the DPPE/PA liposomes significantly increased their stability in blood, but the pH sensitivity was diminished. Polyethylene glycol (PEG)-modified DPPE/PA liposomes were pH-insensitive in buffer, and unstable in blood. However, exchanging PA with the double-chained amphiphile dipalmitoylglycerosuccinate (DPSG) yielded liposomes with improved properties. DPPE/DPSG liposomal GdDTPA-BMA was stable in blood at physiological pH, and displayed a marked pH sensitivity. The pH sensitivity was not diminished after preincubation in blood, contrary to what has been reported for analogues containing unsaturated lipids. The potential of this system for monitoring pH was demonstrated in an in vitro MRI phantom study.

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BloodBuffersCholesterolContrast MediaCryoelectron MicroscopyGadolinium DTPAGlyceridesHumansHydrogen-Ion ConcentrationImage EnhancementLiposomesMagnetic Resonance ImagingMagneticsMaleMicroscopy, ElectronPalmitic AcidPhantoms, ImagingPhosphatidylethanolaminesPolyethylene GlycolsSuccinatesJournal ArticleResearch Support, Non-U.S. Gov't

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BibTeXRIS

Knut-Egil Løkling, Roald Skurtveit, Atle Bjørnerud, Sigrid L Fossheim. 2004. Novel pH-sensitive paramagnetic liposomes with improved MR properties.. https://doi.org/10.1002/mrm.20009

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