Banta:Adsorption

The Effect of Adsorption-Induced Conformational Changes on Structure, Activity and Aggregate Formation of Injectable Biologics

Presently, more than 130 biologically-active pharmaceuticals are approved for clinical use by the FDA. The successful formulation of these biologics is highly dependent on maintaining the stability of the drug throughout its lifecycle. The most common route of administration of these protein and peptide-based drugs is intravenous injection. For such injectables, during storage and delivery, a system is created where solution-based proteins interact with the surface of the container and delivery device. Because proteins have a natural tendency to interact with surfaces, and protein adsorption can result in surface-induced structural perturbation, the stability of such molecules can be compromised, subsequently affecting the clinical safety and efficacy of these pharmaceuticals. The goal of this research is to better understand the effect of surfaces used in medication storage and delivery on the stability of biologically active molecules. Specifically, this will be accomplished by studying the impact that surface-induced conformational changes of proteins have on their structure, activity and tendency to populate non-native, aggregate-prone state. Currently, only limited protein-surface system have been studied to assess the impact of the surface on protein stability, and no general trends or correlations exist relating extent of surface-induced conformational changes to structure and activity loss as well as aggregate formation.