(526c) Encapsulation and Thermal Stability of Immunological Biologics Using Complex Coacervation

A major obstacle when working with biomolecules is their stability at varying temperatures. Relief programs often struggle to transport sufficient vaccines and other cold chain-dependent medical supplies due to the need to keep these materials carefully refrigerated. The cold chain, currently, accounts for 80% of the cost of vaccination and breaks in the cold chain resulting in the loss of nearly half of vaccines produced. Thus, by mitigating the need for the cold chain, vaccine campaigns and disaster relief efforts will no longer be confined by cold chain logistics.

Complex coacervation offers a novel means for the delivery of proteins and other bioactive materials. We hypothesize that control over the chemical and physical aspects of the molecular microenvironment can be used to modulate protein function and stability with the potential to mimic the biological milieu. In particular, we posit that polypeptide-based coacervates can be used to create a highly crowded environment where the chemistry of the polypeptides can be used to tune the stabilizing character of the encapsulating environment. Furthermore, encapsulation via coacervation is a fully aqueous process that is compatible with biologic materials and can achieve extremely high levels of protein encapsulation via preferential partitioning. We have investigated the encapsulation and resulting thermal stability of three model proteins, bovine serum albumin (BSA), hen egg white lysozyme (HEWL), and a novel monoclonal antibody (mAb), into poly(lysine) and poly(glutamate)-based complex coacervates. Encapsulation efficiency of these model systems, specifically lysozyme, has gone as high as 80% with partitioning coefficients above 200. Preliminary results also show that the encapsulated proteins retain their secondary structure. Additionally, data suggests that even at higher temperatures, the secondary structure remains the same. Polypeptide-based coacervates are a powerful platform technology in understanding the role of the chemical environment on the stability of a protein formulation. Ultimately, we look to harvest these materials to enable the development of highly stable therapeutics and biologics such as refrigeration-free vaccines.