Acid-degradable protein delivery vehicles based on metathesis chemistry

Abstract

In this communication we demonstrate that acyclic diene metathesis (ADMET) polymerization is a powerful methodology for the synthesis of acid-degradable polymers based on polyketals and polyacetals. Ten new polyketals and polyacetals were synthesized, using ADMET, and a polyacetal based on anthracene aldehyde was identified, which had the physical properties needed for microparticle formulation. The antioxidant protein catalase was encapsulated into microparticles, formulated from this polyacetal, using a double emulsion procedure, and cell culture studies demonstrated that these microparticles dramatically improved the ability of catalase to scavenge hydrogen peroxide produced by macrophages. We anticipate numerous applications of ADMET for the synthesis of acid-degradable polymers based on its excellent tolerance toward functional groups and ease of synthesis.