Preparation of Polymeric Nanoparticles using Poly(D,L-lactide) grafted Poly(ethylene glycol)-b-Poly(L-seirne) Block Copolymers

Abstract

Core-shell structured nanoparticles of poly(ethylene glycol)-b-[poly(Lserine)-g-poly(D,L-lactide)] (PEG-PSER-PLA) copolymer were prepared. The copolymer had a poly(L-serine) (PSER) block as a linker between a hydrophilic poly(ethylene glycol) (PEG) and a hydrophobic poly(D,L-lactide) (PLA) unit. It 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-(tertbutyl)-L-serine and subsequent removal of tert-butyl groups. Methoxypoly( ethylene glycol)-amine with a MW of 5000 was used as an initiator for the polymerization. The polymerization of D,L-lactide by initiation with PEG-PSER produced a comb-like copolymer, PEG-PSER-PLA. The nanoparticles obtained from PEG-PSER-PLA copolymer had a diameter of ~200 nm and showed a positive zeta potential value of 19.3 mV. The release profile of the nanoparticles prepared from PEG-PSER-PLA was investigated by using 1- aminopyrene. In pH 3.0 phosphate buffer solution at 36 ℃, 1-aminopyrene was more slowly released from the nanoparticles of PEG-PSER-PLA copolymer than those of a linear PEG-PLA copolymer. The nanoparticles of PEG-PSERPLA copolymer showed much better stability than those of a linear PEG-PLA copolymer having a comparable molecular weight in an aqueous solution.