Protein stabilization at high concentrations is a research area of universal interest due to applications in drug delivery of cancer-fighting and other pharmaceutically-relevant proteins. Current delivery methods call for a large (>200 mg) dose to be formulated at a low concentration and administered via IV because at high concentration (above 100 mg/ml), short-range attractive forces result in un-injectable high viscosities and irreversible aggregation of the protein.In previous work, our collaboration demonstrated efficacy of a high concentration (up to 320 mg), low viscosity nanocluster platform for concentrating, storing, and delivering protein therapeutics without gelation. This is done by formulating at a pH close to the isoelectric point of the protein in the presence of a small �crowding� molecule which reduces the intermolecular repulsive forces by minimizing the protein surface charge. The result is a balance of short-ranged attractive forces between individual molecules and long-ranged repulsive forces, allowing the formation of tunable nano-scale protein clusters formed by either concentration of a protein solution or dilution of a lyophilized powder. Here, we demonstrate an extension of our technology to pharmaceutically relevant fragments such as an engineered single-chain T-cell receptor similar in structure to a single-chain variable fragment of an antibody using trehalose as the crowding molecule. We plan to look at how different sizes and charges of molecules lead to different dispersion characteristics, and biocharacterization of the clusters with in vitro and in vivo data will be discussed.

Biochemical characterization of the low viscosity reversible protein nanocluster platform

247th National Meeting (2014)

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