Complex Coacervate Core Micelles for Protein Delivery

Proteins are an increasingly important class of therapeutics. There are, however, several challenges in the development and production of protein based therapeutics. These include relative temperature sensitivity and propensity to aggregate at therapeutically relevant concentrations, both of which contribute to the their relatively short shelf-life and short circulation times. Previous work has developed protein delivery platforms that increase circulation time while maintaining protein activity, but suffer several shortcomings such as low-levels of protein loading and controlled release. To address these limitations, we have investigated the use of block-polyelectrolytes to form complex coacervate core micelles (C3Ms) to be used as a protein delivery vehicle. While C3Ms allow for controlled protein loading and release, they also have the potential to improve protein stability at therapeutically relevant concentrations and increased temperatures. In this work, we identified protein and polymer design parameters that govern complex coacervation of model proteins to form C3Ms that remain phase separated under physiological conditions and study how incorporation of proteins in C3Ms influences protein stability and delivery to cells.