(267a) Structure and Stability of Protein-Rich Polyelectrolyte Complex Micelles

Proteins are an important class of therapeutics, but provide new challenges for their storage, formulation, and delivery. 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 uncontrolled release. To address these limitations, we have investigated the use of block-polyelectrolytes to form protein-rich micelles. This approach relies on the complex coacervation of amphoteric proteins with a block copolymer of opposite charge to self-assemble into polyelectrolyte complex micelles (PECs, also termed complex coacervate core micelles). These micelles could then be used as protein delivery vehicles for therapeutic applications, while also allowing for controlled protein loading and release. Many globular proteins, however, do not form PECs, and those that do only do so over narrow pH and ionic strength ranges. In this work, we identified protein and polymer design parameters that govern complex coacervation of model proteins to form PECs that remain phase separated under physiological conditions and study how incorporation of proteins in PECs influences protein stability and delivery to cells.