Discovery of compounds with viscosity-reducing effects on biopharmaceutical formulations with monoclonal antibodies

Proj, Matic (avtor), Zidar, Mitja (avtor), Lebar, Blaž (avtor), Strašek Benedik, Nika (avtor), Miličić, Goran (avtor), Žula, Aleš (avtor), Gobec, Stanislav (avtor)

For the development of concentrated monoclonal antibody formulations for subcutaneous administration, the main challenge is the high viscosity of the solutions. To compensate for this, viscosity reducing agents are commonly used as excipients. Here, we applied two computational chemistry approaches to discover new viscosity-reducing agents: fingerprint similarity searching, and physicochemical property filtering. In total, 94 compounds were selected and experimentally evaluated on two model monoclonal antibodies, which led to the discovery of 44 new viscosity-reducing agents. Analysis of the results showed that using a simple filter that selects only compounds with three or more charge groups is a good ‘rule of thumb’ for selecting potential viscosity-reducing agents for two model monoclonal antibody formulations.

• Jezik: Angleški jezik
• Ključne besede: viscosity, protein formulations, biopharmaceuticals, viscosity-reducing agents, computational screening
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: Str. 5420-5429
• Številčenje: Vol. 20
• PID: 20.500.12556/RUL-153982
• UDK: 532.13+541.8
• ISSN pri članku: 2001-0370
• DOI: 10.1016/j.csbj.2022.09.035
• COBISS.SI-ID: 123845891
• Datum objave v RUL: 17.01.2024

Gradivo je del revije

• Naslov: Computational and structural biotechnology journal
• Založnik: Elsevier, Research Network of Computational and Structural Biotechnology
• ISSN: 2001-0370
• COBISS.SI-ID: 5068826

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: viskoznost, proteinske formulacije, biofarmacevtski izdelki, sredstva za zmanjševanje viskoznosti, računalniško preverjanje