Investigation of the Allergenic Properties of the Interferon-Lambda 1, Pegylated by Electron-Beam Method

Nikolai Kikhtenko, Larisa Oleynik,Pavel Madonov, Evgeniy Sherstoboev

2020 Cognitive Sciences, Genomics and Bioinformatics (CSGB)(2020)

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摘要
The development of effective antiviral drugs for use in ophthalmic practice is an urgent task of modern medicine. Type III interferons have similar functions with wellknown type I interferons, that is they have antiviral, antitumor and immunomodulating activities. However, their receptors are expressed primarily on epithelial barrier cells, such as mucous membranes. In this regard, type III interferons have less systemic side effects when used for therapeutic purposes. However, interferons are protein molecules, which mean that they are practically not absorbed from gastrointestinal tract, therefore, they need parenteral administration, which reduces patient compliance. It was shown that electron-beam pegylation increases the solubility of the original substances, reduces immunogenic properties, and also increases the oral bioavailability of proteins up to 20%. However, a change of the molecule structure can significantly change both pharmacokinetic and pharmacodynamic properties. In this work the allergenic properties of interferon1, pegylated by electron beam method, were investigated in the systemic anaphylaxis reaction in guinea pigs, and in the active cutaneous anaphylaxis reaction and the conjunctival test in mice. Thus, it was found that pegylated IFN-λ1, obtained by the electron beam method, generally does not have allergenic properties when used in a therapeutic dose or in ten-fold higher dose, in the conditions of the experiments. This creates the prerequisites for the development of a drug based on pegylated IFN-λ1 for the treatment of viral infections of the ocular surface, and it requires further experiments to establish its effectiveness.
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关键词
interferon-lambda,electron-beam method,pegylation
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