期刊
THERANOSTICS
卷 5, 期 5, 页码 489-503出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.10069
关键词
Magnetoliposomes; omega-3 poly-unsaturated fatty acid ethyl ester; Superparamagnetic nanoparticle; MRI; Image guided drug delivery
资金
- SOLUTEX SL
- Spanish Ministry of Economy and Competitivity [SAF2011-23622, IPT-2012-1331-006000, CTQ2013-47669-R]
- Community of Madrid [S2010/BMD-2349]
- Agencia Estatal Consejo Superior de Investigaciones Cientificas (CSIC)
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 (omega-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 omega-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 H-1 NMR Spectroscopy of the liposomal preparations containing omega-3 PUFA-EE revealed well resolved H-1 resonances from highly mobile omega-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) omega-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the incorporation of omega-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra, indicated that the goticules of omega-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 omega-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 omega-3 PUFA-EE may become useful anti-inflammatory agents for image guided drug delivery.
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