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We describe the preparation, physico-chemical characterization and anti-inflammatory properties
of liposomes containing the superparamagnetic nanoparticle Nanotex, the fluorescent dye Rhodamine-
100 and omega-3 polyunsaturated fatty acid ethyl ester (ω-3 PUFA-EE), as theranostic
anti-inflammatory agents. Liposomes were prepared after drying chloroform suspensions of egg
phosphatidylcholine, hydration of the lipid film with aqueous phases containing or not Nanotex,
Rhodamine-100 dye or ω-3 PUFA-EE, and eleven extrusion steps through nanometric membrane
filters. This resulted in uniform preparations of liposomes of approximately 200 nm diameter.
Extraliposomal contents were removed from the preparation by gel filtration chromatography.
High Resolution Magic Angle Spinning 1H NMR Spectroscopy of the liposomal preparations
containing ω-3 PUFA-EE revealed well resolved 1H resonances from highly mobile ω-3 PUFA-EE,
suggesting the formation of very small (ca. 10 nm) ω-3 PUFA-EE nanogoticules, tumbling fast in the
NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the
incorporation of ω-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra,
indicated that the goticules of ω-3 PUFA-EE or its insertion in the membrane did not affect the
average translational diffusion coefficient of water, suggesting an intraliposomal localization, that
was confirmed by ultrafiltration. The therapeutic efficacy of these preparations was tested in two
different models of inflammatory disease as inflammatory colitis or the inflammatory component
associated to glioma development. Results indicate that the magnetoliposomes loaded with ω-3
PUFA-EE allowed MRI visualization in vivo and improved the outcome of inflammatory disease in
both animal models, decreasing significantly colonic inflammation and delaying, or even reversing,
glioma development. Together, our results indicate that magnetoliposomes loaded with ω-3
PUFA-EE may become useful anti-inflammatory agents for image guided drug deliveryThis work was supported in part by grants from
SOLUTEX SL to SC, grants from the Spanish Ministry
of Economy and Competitivity SAF2011-23622,
IPT-2012-1331-006000 to SC, grant CTQ2013-47669-R
to PB, and grant S2010/BMD-2349 from the Community
of Madrid to S.C. and P.B. D.C. and V.N. held
predoctoral contracts from Agencia Estatal Consejo
Superior de Investigaciones Científicas (CSIC
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