Small scale model for predicting transportation-induced particle formation in biotherapeutics

Pečarič Strnad, Urška (avtor), Zalokar, Petra (avtor), Osterman, Natan (avtor), Zidar, Mitja (avtor)

Understanding protein adsorption and aggregation at the air-liquid interfaces of protein solutions is an important open challenge in biopharmaceutical, medical, and biotechnological applications, among others. Proteins, being amphiphilic, adsorb at the surface, partially unfold, and form a viscoelastic film through non-covalent interactions. Mechanical agitation of the surface can break this film up, releasing insoluble protein particles into the solution. These aggregates are usually highly undesirable and even toxic in cases, such as for biopharmaceutical application. Therefore, it is imperative to be able to predict the behavior of such solutions undergoing surface agitation during handling, usually transport or mixing. We apply the findings on the viscoelastic protein f ilm, formed at the air-liquid interface, to the prediction of surface mediated aggregation in selected protein solutions of direct biopharmaceutical relevance. Our broad study of Brewster angle microscopy and aggregation monitoring across multiple size ranges by micro-flow imaging, light scattering, and size exclusion chromatography shows that formation of protein particles is driven by the adsorption rate as compared to the rate of surface turnover and that surface film dynamics in the quiescent phase directly affect aggregation. We demonstrate how these learnings can be directly applied to the design of a novel small scale biopharmaceutical stability study, simulating relevant transport conditions. More generally, we show the impact of adsorption dynamics at the air- liquid interface on the stability of a distinct protein solution, as a general contribution to understanding different colloidal and biological interfacial systems.

• Jezik: Angleški jezik
• Ključne besede: biophysics, proteins, aggregation, adsorption, biopharmaceuticals, viscoelastic films, air-liquid interface
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FMF - Fakulteta za matematiko in fiziko
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2025
• Št. strani: 9 str.
• Številčenje: Vol. 245, art. no. ǂ114304
• PID: 20.500.12556/RUL-164746
• UDK: 577.322
• ISSN pri članku: 0927-7765
• DOI: 10.1016/j.colsurfb.2024.114304
• COBISS.SI-ID: 214266115
• Datum objave v RUL: 08.11.2024

Gradivo je del revije

• Naslov: Colloids and surfaces : Biointerfaces
• Skrajšan naslov: Colloids surf., B Biointerfaces
• Založnik: Elsevier
• ISSN: 0927-7765
• COBISS.SI-ID: 15329029

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: biofizika, proteini, agregacija, adsorpcija, biofarmacevtiki, viskoelastičnost