Lowering Viscosity of Concentrated Aqueous Protein Formulations

Therapeutic proteins are typically administered to patients by injection or intravenous infusion. Since many of these proteins possess relatively low specific biological activities, highly concentrated (>100 mg/mL) aqueous solutions are often required for that. Such aqueous solutions are very viscous, making them difficult to handle and administer. To address this problem, herein we propose to explore the following alternative strategies for lowering viscosity of concentrated aqueous formulations of proteins: (i) using suspensions of protein nanocrystals instead of solutions; and (ii) using suspensions of amorphous protein nanoparticles instead of solutions. These strategies aim to reduce the number and/or the strength of protein-protein interactions that result in transient three-dimensional networks in solution which create resistance to flow, thereby lowering viscosity of the formulation.