We are resolving critical measurement issues that prevent researchers from reliably predicting the chemical and physical storage stability of biomacromolecules (proteins and DNA) in hydrophilic glasses such as those used by the biopharmaceutical industry to produce injectable medications. The analytical methods and theory that we develop will lead to rational formulation of stabilizing glasses, which will, in-turn, facilitate development of drug candidates that are promising but currently unstable, reduce process development costs for stabilizing drugs generally. Additionally, the work will shed light on the physical processes that lead to transport in glassy materials in general, which will, for example, help to predict such things as rates of drug elution from stents.
Work in this project will enable industry to develop rational formulation approaches for freeze-drying, thus facilitating the manufacture safer, longer lasting biopharmaceuticals, with less time and resource cost required for stabilization. Biopharmaceuticals are the fastest growing subsector in pharmaceuticals, and currently generates $120 billion in sales annually; half of new therapeutic proteins will need to be freeze-dried for release, but formulation for freeze-drying is still inefficient and empirical, with only a 60% success rate. Improved analytical methods for characterizing protein stability in freeze-dried glasses, and better theory for understanding degradation routes are sorely needed. We are developing measurements and models to underpin the design and development of freeze-dried glass media that enable the chemical and physical stability of proteins and DNA during storage
This project is an integral part of a cooperative effort led by NIST and partially funded by the National Institutes of Health's National Institute of Biomedical Imaging and Bioengineering. It includes the University of Chicago, the University of Colorado and the University of Connecticut. Owing to the complexity of the protein stabilization problem, we have assembled a multidisciplinary team with world-class standing in each of the research areas needed. We use theory, simulation and experimentation to develop a clear understanding of key relationships between glass properties and likely stability outcomes of proteins in the glasses. We develop analytical methods to unambiguously and precisely measure the glass properties of interest. We validate the theoretical models by carrying out stability studies of model compounds and of pharmaceutically important proteins in fully characterized hydrophilic glasses. The theory, simulation, physical characterization and pharmaceutical studies are coordinated so that
MT Cicerone, JF Douglas, β relaxation governs protein stability in sugar-glass matricies, Soft Matter 8 (10), 2983 (1012).
J Giri, W-J Li, RS Tuan, MT Cicerone, Stabilization of proteins by nanoencapsulation in sugar–glass for tissue engineering and drug delivery applications, Advanced Materials 23 (42),4861-4867 (2011).
MT Cicerone, Q Zhong, J Johnson, KA Aamer, M Tyagi, Surrogate for Debye–Waller factors from dynamic Stokes shifts, The Journal of Physical Chemistry Letters, 2(12), 1464-1468 (2011).