Microfluidic and nanotechnology based assays for the development of safe biopharmaceuticals
July 14-17, 2019
Protein stability towards aggregation represents a potential challenge for the production and administration of pharmaceuticals. In particular, aggregation can compromise the developability and shelf-life of the products, with consequences for yield and safety, respectively. In this work, we discuss two novel approaches for the analysis of the stability of protein formulations:
(1) A microfluidic diffusion-sizing platform to analyze protein sizes and interactions at high protein concentration directly in the solution state with minimal perturbation of the sample. The limited dilution of the sample during the analysis and the possibility to characterize properties directly in the solution state make the technique suitable for the analysis of heterogeneous solutions of proteins under dynamic equilibrium. We show how the platform represents an attractive tool for the analysis of sizes and interactions of proteins in both diluted and high-concentration solutions during development, manufacturing, and formulation.
(2) A highly controlled assay of surface-induced protein aggregation based on nanoparticles. Protein aggregation is often due to heterogeneous nucleation events occurring at interfaces, including air/water interface, impurities and leachable particles. However, the development of screening tools against surface aggregation has been hindered by the difficulty in generating a controlled amount of surface stress in the formulation as well as in decoupling the surface effect from the contribution of hydrodynamic flows. In our assay, we leverage the flexibility of polymer chemistry to finely tune the properties and amount of surfaces provided by the nanoparticles, inducing aggregation of soluble peptides and proteins, including antibodies, in a time scale of a few hours. This platform represents i) an attractive tool for fundamental studies of heterogeneous nucleation events under stagnant and flow conditions, and ii) a high-throughput screening assay of the effect of intrinsic and extrinsic variables on protein stability towards interface-induced aggregation.
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Paolo Arosio, Marie R.G. Kopp, Marta Virginia Zucca, Umberto Capasso Palmiero, Alessia Villois, Adriana-Michelle Wolf Pérez, Brigitte Friedrichsen, and Nikolai Lorenzen, "Microfluidic and nanotechnology based assays for the development of safe biopharmaceuticals" in "Biological and Pharmaceutical Complex Fluids III: Protein Self-Assembly, Rheology and Interfacial Properties", Samiul Amin, Manhattan College, USA Miguel Rodrigues, University of Lisbon, Portugal Paolo Arosio, ETHZ, Switzerland Eds, ECI Symposium Series, (2019). https://dc.engconfintl.org/bpcf_iii/20