| Abstract
| - Maghemite (γ-Fe2O3) nanocrystals stable at neutral pH and in isotonic aqueous media weresynthesized and encapsulated within large unilamellar vesicles of egg phosphatidylcholine (EPC) anddistearoyl-SN-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG2000, 5mol %), formed by film hydration coupled with sequential extrusion. The nonentrapped particles wereremoved by flash gel exclusion chromatography. The magnetic-fluid-loaded liposomes (MFLs) werehomogeneous in size (195 ± 33 hydrodynamic diameters from quasi-elastic light scattering). Iron loadingwas varied from 35 up to 167 Fe(III)/lipid mol %. Physical and superparamagnetic characteristics of theiron oxide particles were preserved after liposome encapsulation as shown by cryogenic transmissionelectron microscopy and magnetization curve recording. In biological media, MFLs were highly stable andavoided ferrofluid flocculation while being nontoxic toward the J774 macrophage cell line. Moreover, stericstabilization ensured by PEG-surface-grafting significantly reduced liposome association with the macrophages. The ratios of the transversal (r2) and longitudinal (r1) magnetic resonance (MR) relaxivities ofwater protons in MFL dispersions (6 < r2/r1< 18) ranked them among the best T2 contrast agents, thehigher iron loading the better the T2 contrast enhancement. Magnetophoresis demonstrated the possibleguidance of MFLs by applying a magnetic field gradient. Mouse MR imaging assessed MFLs efficiency ascontrast agents in vivo: MR angiography performed 24 h after intravenous injection of the contrast agentprovided the first direct evidence of the stealthiness of PEG-ylated magnetic-fluid-loaded liposomes.
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