Infusion-based solutions contribute to the stability of recombinant antibody and virus: Insights for formulation development.

Abstract

Protein-based biologics exhibit protein aggregation and loss of efficacy due to physical stress during manufacture, storage, and administration. Therefore, controlling the stresses applied in these processes is critical for maintaining product quality and therapeutic efficacy. Infusion solutions are an alternative source of nutrition for patients who are unable to receive adequate enteral nutrition. They contain excipients that help protect the protein structure. We hypothesized that infusion solutions could be used to maintain the quality and therapeutic efficacy of biologics formulations or as prototype systems for formulation optimization. In this study, we evaluated the effects of infusion-based solutions on recombinant trastuzumab and herpes simplex virus type 1 (HSV-1), two cancer therapy biologics. Among the tested solutions, a parenteral nutrition-based solution exhibited the strongest protective effects on the recombinant trastuzumab under stirring, indicated by enhanced protein solubility and fewer aggregated particles compared with those in the control (Dulbecco's phosphate-buffered saline, D-PBS). For antibodies in the parenteral nutrition-based solution, hydrophobic surface patch areas were smaller, whereas zeta potentials, indicating molecular repulsion, were more positive than those in D-PBS. Therefore, antibody hydrophobic interactions decreased and colloidal stability increased in the nutrition-based solution. Similarly, under combined agitation and freeze-thaw stress, and long-term refrigerated storage, the solution maintained high HSV-1 infectivity. Collectively, our findings demonstrated that infusion-based solutions can effectively stabilize a recombinant antibody and virus under clinically relevant stresses. This approach provides a strategy for improving the robustness of biologics formulations.