A Nanoparticle-Based Assay To Evaluate Surface-Induced Antibody Instability.

摘要: Protein stability against aggregation represents a major quality attribute for the successful development of biopharmaceuticals. Increasing evidence indicates that formation protein aggregates in aqueous solutions is often triggered by interactions between proteins and interfaces. Yet, contrast to large number methods available test bulk properties, high-throughput assays investigate instability at interfaces remain much less developed. Major challenges include control amount type surfaces, as well presence synergistic effects hydrodynamic flows. Here, we describe develop highly controlled surface-mediated stress assay based on polymeric nanoparticles. We show hydrophobic nanoparticles are remarkably powerful destabilizing such antibodies. further this approach can be implemented microfluidic platform compartmentalizing solution picoliter droplets surrounded an oil phase. Our method allows evaluation time scale minutes requires amounts sample order few hundred micrograms. demonstrate our good mimic air-water finds application screening tool optimize toward surface-induced aggregation. provide concrete example identifying optimal concentration range Tween 80 prevents antibody Overall, nanoparticle (HNSSA) attractive accelerated tests under both stagnant flow conditions, with implications optimization buffer composition selection stable biotherapeutic candidate molecules during early stage development.