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Open AccessArticle

Two-Step Size-Exclusion Nanofiltration of Prothrombin Complex Concentrate Using Nanocellulose-Based Filter Paper

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Nanotechnology and Functional Materials, Department of Materials Science and Engineering, Uppsala University, Box 534, 751 21 Uppsala, Sweden
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Nacimbio JC, 10, 2nd Volkonsky lane, 127473 Moscow, Russia
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Biopharmgarant LLC, Stancionnaya 45, 600901 Vladimir, Russia
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National Research Center for Hematology, Novyi Zykovskiy proezd 4, 125167 Moscow, Russia
*
Author to whom correspondence should be addressed.
Biomedicines 2020, 8(4), 69; https://doi.org/10.3390/biomedicines8040069
Received: 29 February 2020 / Revised: 16 March 2020 / Accepted: 21 March 2020 / Published: 26 March 2020
(This article belongs to the Section Nanotechnology and Biotechnology)
Coagulation Factor IX-rich protrhombin complex concentrate (FIX-PCC) is a therapeutic biologic product that consists of a mixture of several human plasma-derived proteins, useful for treating hemophilia B. Due to its complex composition, FIX-PCC is very challenging to bioprocess through virus removing nanofilters in order to ensure its biosafety. This article describes a two-step filtration process of FIX-PCC using a nanocellulose-based filter paper with tailored porosity. The filters were characterized with scanning electron microscopy (SEM), cryoporometry with differential scanning calorimetry, and nitrogen gas sorption. Furthermore, in order to probe the filter’s cut-off size rejection threshold, removal of small- and large-size model viruses, i.e., ΦX174 (28 nm) and PR772 (70 nm), was evaluated. The feed, pre-filtrate, and permeate solutions were characterized with mass-spectrometric proteomic analysis, dynamic light scattering (DLS), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and analytical size-exclusion high-performance liquid chromatography (SEHPLC). By sequential filtration through 11 μm pre-filter and 33 μm virus removal filter paper, it was possible to achieve high product throughput and high virus removal capacity. The presented approach could potentially be applied for bioprocessing other protein-based drugs. View Full-Text
Keywords: Mille-feuille filter; Cladophora cellulose; hemophilia B; protein aggregates; virus removal filtration Mille-feuille filter; Cladophora cellulose; hemophilia B; protein aggregates; virus removal filtration
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MDPI and ACS Style

Manukyan, L.; Mantas, A.; Razumikhin, M.; Katalevsky, A.; Golubev, E.; Mihranyan, A. Two-Step Size-Exclusion Nanofiltration of Prothrombin Complex Concentrate Using Nanocellulose-Based Filter Paper. Biomedicines 2020, 8, 69.

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