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Characterisation of protein aggregation with the Smoluchowski coagulation approach for use in biopharmaceuticals

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Abstract

Protein aggregation is a field of increasing importance in the biopharmaceutical industry. Aggregated particles decrease the effectiveness of the drug and are associated with other risks, such as increased immunogenicity. This article explores the possibility of using the Smoluchowski coagulation equation and similar models in the prediction of aggregate-particle formation. Three different monoclonal antibodies, exhibiting different aggregation pathways, are analysed. Experimental data are complemented with aggregation dynamics calculated by a coagulation model. Different processes are implemented in the coagulation equation approach, needed to cover the actual phenomena observed in the aggregation of biopharmaceuticals, such as the initial conformational change of the native monomer and reversibility of smaller oligomers. When describing the formation of larger particles, the effect of different aggregation kernel parameters on the corresponding particle size distribution is studied. A significant impact of the aggregate fractal nature on overall particle size distribution is also analysed. More generally, this work is aimed to establish a mesoscopic phenomenological approach for characterisation of protein aggregation phenomena in the context of biopharmaceuticals, capable of covering various aggregate size scales from nanometres to micrometres and reach large time-scales, up to years, as needed for drug development.

Graphical abstract: Characterisation of protein aggregation with the Smoluchowski coagulation approach for use in biopharmaceuticals

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Publication details

The article was received on 04 May 2018, accepted on 06 Jun 2018 and first published on 04 Jul 2018


Article type: Paper
DOI: 10.1039/C8SM00919H
Citation: Soft Matter, 2018, Advance Article
  • Open access: Creative Commons BY license
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    Characterisation of protein aggregation with the Smoluchowski coagulation approach for use in biopharmaceuticals

    M. Zidar, D. Kuzman and M. Ravnik, Soft Matter, 2018, Advance Article , DOI: 10.1039/C8SM00919H

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