title: Pegylated nanoliposomes remote-loaded with the antioxidant tempamine ameliorate experimental autoimmune encephalomyelitis.
abstract: Reactive oxygen species are involved in the pathogenesis of multiple sclerosis (MS), Parkinson's disease and neurodegenerative diseases. Here we report that Tempamine (TMN), a stable radical with antioxidant and proapoptotic activities, when encapsulated in the intraliposome aqueous phase of pegylated (<100 nm) nanoliposomes (nSSL), is efficient in inhibiting experimental autoimmune encephalomyelitis (EAE) in mice. The TMN is remote-loaded into nSSL by an intraliposome high/extraliposome low transmembrane ammonium sulfate gradient. Biodistribution studies of nSSL-TMN labeled with the liposome non transferable non metabolizable (3)H-cholesteryl hexadecyl ether show that almost 3% of the injected dose of liposomes reached the brain of the EAE mice, compared with less than 1% in the control healthy mice. This accumulation in the brain, combined with the fact that TMN demonstrates a controlled slow release out of the nSSL, may explain the superior therapeutic activity of nSSL-TMN over free TMN. Our results suggest that the study of nSSL-TMN for therapy of MS, and other neurodegenerative diseases involving oxidative damage, is worth pursuing.
authors: Laboratory of Membrane and Liposome Research, Department of Biochemistry, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors: Pablo
authors: P
authors: Kizelsztein
authors: Haim
authors: H
authors: Ovadia
authors: Olga
authors: O
authors: Garbuzenko
authors: Alex
authors: A
authors: Sigal
authors: Yechezkel
authors: Y
authors: Barenholz
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003497:Cyclic N-Oxides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004058:Diffusion; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D008081:Liposomes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051379:Mice; D053769:Nanocapsules / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013451:Sulfonic Acids / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D008081:Liposomes; D053769:Nanocapsules; D017382:Reactive Oxygen Species; D013451:Sulfonic Acids; C015527:4-amino-TEMPO; D011092:Polyethylene Glycols; C005741:sulfamic acid