Synthesis of Polyethylene Glycol–Poly(glycerol carbonate) Block Copolymeric Micelles as Surfactant-Free Drug Delivery Systems
Danielle M. Fitzgerald, Heng Zhang, Catalina Bordeianu, Yolonda L. Colson, Mark W. Grinstaff
Abstract
We report the synthesis of block copolymers of monomethoxylated polyethylene glycol and poly(glycerol carbonate) (mPEG- b -PGC) via the ring-opening polymerization of benzyl glycidyl ether, monomethoxylated polyethylene glycol, and carbon dioxide using a cobalt salen catalyst. The resulting block copolymers display high polymer/cyclic carbonate selectivity (>99%) and, if two oxirane monomers are used, random incorporation into the polymer feed. The resulting diblock mPEG- b -PGC polymer shows promise as a nanocarrier for surfactant-free, sustained chemotherapeutic delivery. mPEG- b -PGC, with paclitaxel conjugated to the pendant primary alcohol of the glycerol polymer backbone, readily forms 175 nm diameter particles in solution and contains 4.6 wt % paclitaxel (PTX), which is released over 42 days. The mPEG- b -PGC polymer itself is noncytotoxic, whereas the PTX-loaded nanoparticles are cytotoxic to lung, breast, and ovarian cancer cell lines.