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Merck
  • Pegylated nanoliposomes remote-loaded with the antioxidant tempamine ameliorate experimental autoimmune encephalomyelitis.

Pegylated nanoliposomes remote-loaded with the antioxidant tempamine ameliorate experimental autoimmune encephalomyelitis.

Journal of neuroimmunology (2009-07-01)
Pablo Kizelsztein, Haim Ovadia, Olga Garbuzenko, Alex Sigal, Yechezkel Barenholz
초록

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.

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Sigma-Aldrich
4-Amino-TEMPO, free radical, 97%