期刊
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
卷 32, 期 4, 页码 178-184出版社
MARY ANN LIEBERT INC
DOI: 10.1089/jir.2011.0048
关键词
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Currently, products containing interferon beta (IFN beta) are injected either intramuscularly or subcutaneously. To avoid the necessity of injection, we developed a novel monomeric Fc fusion protein of IFN beta (IFN beta Fc) that is absorbed via an immunoglobulin transport system present in the upper and central airways upon administration of the drug as an inhaled aerosol. The systemic absorption of IFNbFc through the lung in non-human primates, at deposited doses of 1, 3, and 10 mu g/kg, was compared to the absorption of a single 3 mu g/kg dose of IFN beta-1a (Avonex (R)) subcutaneously administered. IFNbFc was well absorbed through the lung, displaying dose proportional increases in serum concentrations, and was biologically active, as shown by increases in plasma neopterin levels. The circulating half-life of IFN beta Fc was similar to 3 times longer (similar to 30 h) than that of IFN beta-1a, (8-9 h). At approximately equimolar doses of IFN beta Fc (10 mu g/kg) and IFN beta-1a (3 mu g/kg), the stimulation of neopterin over background levels was approximately equivalent, demonstrating that the longer half-life of IFN beta Fc compensated for the lower relative specific antiviral activity of IFNbFc measured in vitro. In conclusion, IFN beta Fc was efficiently absorbed after pulmonary delivery in non-human primates, retained its biological activity, and may offer a convenient alternative to injectable IFN beta.
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