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Vol 34(2018) N 2 p. 37-46; DOI 10.21519/0234-2758-2018-34-2-37-46
Е.А. Zvonova1,2*, О.А. Ershova1, А.V. Ershov1, А.А. Kazarov1, E.S. Belyanina1, M.V. Lykov1, А.Yu. Vishnevskii1, A.P. Karpov3, S.V. Ruchko3, А.M. Shuster1, А.А. Soloviev2, and I.V. Goldenkova-Pavlova4

PASylation Technology Improves Recombinant Human Interferon Beta-1b Pharmacokinetic Properties in vivo

1The International Biotechnology Center (IBC) Generium, 601125, Volginskii poselok, Petushinskii region, Vladimirskaya oblast Russia
2The Russian State Agrarian University-Moscow Timiriazev Agricultural Academy, 127550, Moscow Russia
3Cellthera Pharm, 601125, Volginskii poselok, Petushinskii region, Vladimirskaya oblast, Russia
4The Institute for Plant Physiology, Russian Academy of Sciences, 127276 Moscow, Russia

*berkovich@ibcgenerium.ru
Received - 17.01.2018; Accepted - 26.02.2018

References

A modified form of the IFNβ-lb protein has been obtained using the PASylation® technology to overcome the constraints associated with the short exposition of the protein in systemic circulation due to the small size of its molecule. To obtain a recombinant IFNβ1b-PAS2OO protein, a PAS polypeptide of 200 amino acid residues was appended to the IFNβ-lb protein using standard molecular biology methods. We conducted a comparative pharmacokinetic study of IFNβ1b-PAS2OO after a single administration to Sprague Dawley rats. It was shown that the introduction of the IFNβ1b-PAS2OO polypeptide in the animals' organisms resulted in the 2-fold increase in the plasma half-life of the preparation and 3-fold growth of AUClast in comparison with the unmodified IFNβ-lb. It was also shown that the PASylation had no significant influence on subcutaneous or intramuscular bioavailability of the cytokine. Our results demonstrate that PASylation® has positive impact on the IFNβ-lb pharmacokinetic properties and can be used for the development of a half-life-extended form of IFNβ-lb, possibly using even longer PAS polypeptides.

interferon beta-1b, PASylation, pharmacokinetic studies



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