This Small Business Innovation Research (SBIR) Phase II project will advance the recent discovery of an ambient temperature dehydration method "Microglassification" that is designed to more efficiently stabilize biomolecules for preservation. Lyophilization is the current process of choice, but it has major disadvantages including high capital cost of equipment, high energy costs, and long process time. Furthermore, with the advent of new protein therapeutics, diagnostics, vaccines, such expensive and environment-sensitive biomolecules can be irreversibly impacted due to the stresses of the freezing and the drying process and may never reach the market due to insufficient stability or even degradation that makes them antigenic and toxic in the body. Incorporation of Microglassification to produce a dry formulation of a biomolecule leads to following benefits: reduction in operation costs, production time savings, increased yield and purity, increased long-term stability, and reduced capital equipment costs.
The broader impacts of this research are not limited to broader temperature tolerances for the microglassified products facilitating storage and transport of sensitive biologics throughout the US, and also to developing countries. But also this research furthers the fundamental understanding of water removal from a protein (how molecular layers of water of hydration influence protein activity), the structural changes that might occur in the protein, and the protein interactions with its surrounding environment. It is expected that Microglassification will provide the needed stability to enable a biotechnological advance to reach the market, and, more importantly, reach the patient.
Microglassification™ is a process that gently removes water from solutions of proteins, or other biologics, resulting in solid, spherical, amorphous microbeads. In this dry state, biologics are often stable enough for long-term storage, transport, or incorporation into drug delivery formulations. The process uses compatible solvents to gently dissolve water away from the protein without exposing it to high temperatures or harsh interfaces. The final product is a pure protein microbead (~1 g/ml) that rapidly dissolves back into solution for use. During this project, we conducted several case studies, focused on identifying changes in protein structure and enzymatic activity, and how to control these changes by incorporating stabilizers into the process. Structural changes were similar to those observed in freeze-dried samples, and were reversible upon rehydration. Microglassification™ of enzymes resulted in minimal, if any, loss in activity. Single-particle studies have allowed us to study water removal as a function of water activity in the dehydration medium, and to correlate this to protein structural stability. These studies have increased our fundamental understanding of particle formation resulting from droplet dehydration. We are preparing two manuscripts to detail the scientific knowledge gained from this research. During this project, we have actively trained undergraduates and emerging engineering professionals by providing industrial research experience, and have supported educational activities through our Duke collaboration. As an extension of this technology, we have begun investigating the use of Microglassified™ therapeutics in controlled release applications. The stabilized particles produced by Microglassification™ may be ideal for drug delivery applications in which the biologic must be encapsulated in a matrix, such as a biodegradable polymer. We are currently investigating an initial application with an industry partner. If successful, this process could be applied to any therapeutic requiring long-term delivery (weeks to months).
