Synthesis of poly(ethylene glycol)/polypeptide/poly(D ,L -lactide) copolymers and their nanoparticles

Abstract

Core-shell structured nanoparticles of poly(ethylene glycol) (PEG)/polypeptide/poly(D,L-lactide) (PLA) copolymers were prepared and their properties were investigated. The copolymers had a poly(L-serine) or poly(L-phenylalanine) block as a linker between a hydrophilic PEG and a hydrophobic PLA unit. They formed core-shell structured nanoparticles, where the polypeptide block resided at the interface between a hydrophilic PEG shell and a hydrophobic PLA core. In the synthesis, poly(ethylene glycol)-b-poly(L-serine) (PEG-PSER) was prepared by ring opening polymerization of N-carboxyanhydride of O-(tert-butyl)-L-serine and subsequent removal of tert-butyl groups. Poly(ethylene glycol)-b-poly(L-phenylalanine) (PEG-PPA) was obtained by ring opening polymerization of N-carboxyanhydride of L-phenylalanine. Methoxy-poly(ethylene glycol)-amine with a MW of 5000 was used as an initiator for both polymerizations. The polymerization of D,L-lactide by initiation with PEG-PSER and PEG-PPA produced a comb-like copolymer, poly(ethylene glycol)-b-[poly(L-serine)-g-poly(D,L-lactide)] (PEG-PSER-PLA) and a linear copolymer, poly(ethylene glycol)-b-poly(L-phenylalanine)-b-poly(D,L-lactide) (PEG-PPA-PLA), respectively. The nanoparticles obtained from PEG-PPA-PLA showed a negative zeta potential value of −16.6 mV, while those of PEG-PSER-PLA exhibited a positive value of about 19.3 mV. In pH 7.0 phosphate buffer solution at 36 °C, the nanoparticles of PEG/polypeptide/PLA copolymers showed much better stability than those of a linear PEG-PLA copolymer having a comparable molecular weight. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011