Organocatalytic Synthesis and Evaluation of Polycarbonate Pendant Polymer:β-Cyclodextrin-Based Nucleic Acid Delivery Vectors

Abstract

A family of mPEG-b-polycarbonate (mPEG-PC) diblock pendant polymers were synthesized from trimethylene carbonate and other cyclic carbonate monomers bearing hydrophobic guest ligands via organocatalytic ring-opening polymerization using 1,4,5-triazabicyclo[4.4.0]dec-5-ene catalyst or 1,8-diazabicyclo[5.4.0]undec-7-ene/thiourea cocatalyst. Diblock copolymers composed of a methoxypoly(ethylene oxide) (mPEG) block and a polycarbonate block containing either homopolymer or mixed polycarbonates (PC) were prepared by homopolymerization or copolymerization of the cyclic carbonate monomers in the presence of mPEG2000 or mPEG5000 initiator to give materials having a tunable pendant group density along the polycarbonate backbone. Polycarbonate blocks targeting the 2.4–10 kDa range were prepared with good molecular weight control and modest polydispersities (averaging ∼1.3). Complexation of plasmid DNA with β-cyclodextrin–polyethylenimine2.5 kDa produced nanoparticle cores that were then coated with the mPEG–PC dibl...