Synthesis and Biological Evaluation of a Degradable Trehalose Glycopolymer Prepared by RAFT Polymerization

There is a significant need for new biodegradable protein stabilizing polymers. Herein, the synthesis of a polymer with trehalose side chains and hydrolytically degradable backbone esters and its evaluation for protein stabilization and cytotoxicity are described. Specifically, an alkene‐containing parent polymer is synthesized by reversible addition–fragmentation chain transfer polymerization, and thiolated trehalose is installed using a radical‐initiated thiol–ene reaction. The stabilizing properties of the polymer are investigated by thermally stressing granulocyte colony‐stimulating factor (G‐CSF), which is expressed and purified using a custom‐designed G‐CSF fusion protein with a polyhistidine‐tagged maltose binding protein. The degradable polymer is shown to stabilize G‐CSF to 66% after heating at 40 °C. Poly(5,6‐benzo‐2‐methylene‐1,3‐dioxepane (BMDO)‐co‐butyl methacrylate‐trehalose) is degraded and its cellular compatibility is investigated. While the polymer is noncytotoxic, cytotoxic effects are observed from the degraded products in fibroblasts and murine myeloblasts. These data provide important information for future use of BMDO‐containing trehalose glycopolymers for biomedical applications. A novel degradable trehalose polymer containing 5,6‐benzo‐2‐methylene‐1,3‐dioxepane is prepared using postpolymerization thiol–ene chemistry. The therapeutic protein granulocyte colony‐stimulating factor (G‐CSF) is expressed and purified, and the degradable trehalose polymer is shown to stabilize G‐CSF against heat stress. Although the parent polymer is cytocompatible, the products of hydrolytic degradation demonstrate cytotoxicity at high concentrations providing the working concentrations for the polymer.