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One-Pot Synthesis of PEG–Poly(amino acid) Block Copolymers Assembling Polymeric Micelles with PEG-Detachable Functionality

Research paper by Takuya Miyazaki, Kazunori Igarashi, Yu Matsumoto, Horacio Cabral

Indexed on: 06 Feb '19Published on: 22 Jan '19Published in: ACS Biomaterials Science & Engineering



Abstract

Block copolymers composed of poly(ethylene glycol) (PEG) and poly(amino acids) (PAA) segments have shown exceptional features for developing biocompatible nanostructures. While the conventional methods for synthesizing PEG–PAA provide excellent control of the degree of polymerization and polydispersity, these protocols involve several steps, which increase the time and costs, and reduce the number of possible block copolymer designs. In this study, we developed a one-pot synthetic method for PEG–PAA block copolymers by doing sequential ring-opening polymerizations (ROP) of ethylene oxide (EO) and the N-carboxyanhydrides (NCAs) of amino acids promoted by the organic base 1,1,3,3-tetramethylguanidine (TMG) as the catalyst. The procedure was effectively used to synthesize PEG-poly(benzyl-l-glutamate) (PEG–PBLG) and PEG-poly(l-Lysine) (PEG–PLL) with narrow molecular weight distribution, comparable to that of block copolymers synthesized by the conventional method initiating the ROP of NCA by amine-terminated PEG. The resulting block copolymers present an ester bond between the PEG and the PAA segments, which can be gradually hydrolyzed in physiological conditions, being advantageous for improving the biocompatibility. Besides, we confirmed that the one-pot PEG–PBLG self-assembled into micelles in aqueous conditions, which showed comparable blood circulation and biodistribution to the micelles prepared from conventional PEG–PBLG. These results indicate the high potential of our one-pot synthetic approach for preparing hydrolyzable PEG–PAAs for constructing supramolecular assemblies.

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