title: Magnetoliposomes loaded with poly-unsaturated fatty acids as novel theranostic anti-inflammatory formulations.
abstract: 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 (1)H NMR Spectroscopy of the liposomal preparations containing ω-3 PUFA-EE revealed well resolved (1)H 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 delivery.
authors.affiliation: 1. Instituto de Investigaciones Biomédicas "Alberto Sols" CSIC/UAM, c/Arturo Duperier 4, Madrid 28029, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Calle
authors.affiliation: 1. Instituto de Investigaciones Biomédicas "Alberto Sols" CSIC/UAM, c/Arturo Duperier 4, Madrid 28029, Spain. ; 2. Laboratorio de Síntesis Orgánica e Imagen Molecular por Resonancia Magnética, Facultad de Ciencias, UNED, Unidad Asociada al CSIC, c/ Paseo Senda del Rey 9, Madrid 28040, Spain.
authors.forename: Viviana
authors.initials: V
authors.lastname: Negri
authors.affiliation: 2. Laboratorio de Síntesis Orgánica e Imagen Molecular por Resonancia Magnética, Facultad de Ciencias, UNED, Unidad Asociada al CSIC, c/ Paseo Senda del Rey 9, Madrid 28040, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Ballesteros
authors.affiliation: 1. Instituto de Investigaciones Biomédicas "Alberto Sols" CSIC/UAM, c/Arturo Duperier 4, Madrid 28029, Spain.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Cerdán
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D055598:Chemical Phenomena; D003092:Colitis / Q000175:diagnosis* / Q000188:drug therapy; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage*; D005456:Fluorescent Dyes; D005910:Glioma / Q000175:diagnosis* / Q000188:drug therapy; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008810:Mice, Inbred C57BL
chemical_list: D000893:Anti-Inflammatory Agents; D005231:Fatty Acids, Unsaturated; D005456:Fluorescent Dyes; D008081:Liposomes; D058185:Magnetite Nanoparticles
keywords: Image guided drug delivery.; MRI; Magnetoliposomes; Superparamagnetic nanoparticle; ω-3 poly-unsaturated fatty acid ethyl ester