Maintaining the viability of vaccines and other therapeutic biomolecules presents a continued problem for relief programs and medicinal practice. The pharmaceutical industry’s critical reliance on refrigeration to maintain therapeutic efficacy results in almost half of vaccines being discarded annually due to breaks in the cold chain. To overcome this, we propose the use of polypeptide-based complex coacervation as a formulation strategy to concentrate and stabilize biomacromolecules. Complex coacervation is a liquid-liquid phase separation that utilizes electrostatics and entropy to encapsulate target moieties without the use of chemical crosslinking or harsh organic solvents. Complex coacervation enables the sequestration of therapeutic cargo with very high levels of partitioning and encapsulation efficiency. Despite the important role of charge, the use of two-polymer coacervates allows for the encapsulation of even weakly charged biologics at a variety of different conditions, even near their isoelectric point. We studied how variations in the overall composition, solution pH, and how the patterning of charges on the complexing polypeptides affected the partitioning and encapsulation of model proteins, including bovine serum albumin, hen egg white lysozyme, human hemoglobin, and the caspase family of enzymes. Furthermore, we extended our study to include the formulation of porcine parvovirus (PPV) and bovine viral diarrhea virus (BVDV) as model viruses. In particular, incorporation of PPV into complex coacervates resulted in a 100-fold increase in stability during accelerated aging studies at 60°C. This improvement in thermal stability strongly suggests the potential of coacervation-based strategies to decrease our reliance on the cold chain. These results provide a strong foundation toward creating thermally stable therapeutics using complex coacervation as a gentle, purely aqueous method of sequestering novel targets.

Protein and virus formulation: Stepping stones toward thermal stability

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.