(162ak) Complex Coacervation for Protein Delivery

Proteins are an important class of biologics in therapeutic development. Their clinical utility, however, is often limited due to their relative temperature sensitivity and propensity to aggregate at therapeutically relevant concentrations; both of which contribute to their relatively short shelf life and high cost. Additionally, previous work to develop protein-based therapeutics has sought to increase circulation time while maintaining protein activity, but these platforms often suffer several shortcomings such as controlled protein loading and release. In this work, we developed coacervate core micelles (C3Ms) that could be used as a protein delivery vehicle for therapeutic applications. We identified protein and polymer design characteristics that govern complex coacervation to form uniform C3Ms that are < 150 nm in diameter and remain colloidally stable. Incorporating a model fluorescent proteins into C3Ms enabled protein encapsulation at high concentrations (>100 mg/mL protein) while maintaining protein activity. Additionally, C3Ms formed with a model fluorescent protein remain phase separated under physiological conditions, allowing us to study protein delivery in vivo.