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The Biological Potential Hidden in Inclusion Bodies

1
Department of Ruminant Production, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), 08140 Caldes de Montbui, Spain
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Drug Delivery & Targeting, CIBBIM-Nanomedicine, Vall d’Hebron Institut of Research (VHIR), Universitat Autònoma de Barcelona (UAB), 08035 Barcelona, Spain
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Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 08035 Barcelona, Spain
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i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-180 Porto, Portugal
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INEB-Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-180 Porto, Portugal
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Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain
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Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain
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Laboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, University of Leuven, 3000 Leuven, Belgium
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2020, 12(2), 157; https://doi.org/10.3390/pharmaceutics12020157
Received: 21 January 2020 / Revised: 12 February 2020 / Accepted: 13 February 2020 / Published: 15 February 2020
Inclusion bodies (IBs) are protein nanoclusters obtained during recombinant protein production processes, and several studies have demonstrated their potential as biomaterials for therapeutic protein delivery. Nevertheless, IBs have been, so far, exclusively sifted by their biological activity in vitro to be considered in further protein-based treatments in vivo. Matrix metalloproteinase-9 (MMP-9) protein, which has an important role facilitating the migration of immune cells, was used as model protein. The MMP-9 IBs were compared with their soluble counterpart and with MMP-9 encapsulated in polymeric-based micelles (PM) through ionic and covalent binding. The soluble MMP-9 and the MMP-9-ionic PM showed the highest activity values in vitro. IBs showed the lowest activity values in vitro, but the specific activity evolution in 50% bovine serum at room temperature proved that they were the most stable format. The data obtained with the use of an air-pouch mouse model showed that MMP-9 IBs presented the highest in vivo activity compared to the soluble MMP-9, which was associated only to a low and a transitory peak of activity. These results demonstrated that the in vivo performance is the addition of many parameters that did not always correlate with the in vitro behavior of the protein of interest, becoming especially relevant at evaluating the potential of IBs as a protein-based nanomaterial for therapeutic purposes. View Full-Text
Keywords: inclusion body; polymeric micelle; stability; matrix metalloproteinase-9; in vitro; in vivo inclusion body; polymeric micelle; stability; matrix metalloproteinase-9; in vitro; in vivo
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Gifre-Renom, L.; Seras-Franzoso, J.; Rafael, D.; Andrade, F.; Cano-Garrido, O.; Martinez-Trucharte, F.; Ugarte-Berzal, E.; Martens, E.; Boon, L.; Villaverde, A.; Opdenakker, G.; Schwartz, S., Jr.; Arís, A.; Garcia-Fruitós, E. The Biological Potential Hidden in Inclusion Bodies. Pharmaceutics 2020, 12, 157.

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