A twin-tailed tadpole-shaped amphiphilic copolymer of poly(ethylene glycol) and cyclic poly(ε-caprolactone): synthesis, self-assembly and biomedical applications

Abstract

A tadpole-shaped amphiphilic copolymer containing cyclic hydrophobic poly(ε-caprolactone) (PCL) and two hydrophilic poly(ethylene glycol) (PEG) tails, PEG-b-(c-PCL)-b-PEG, was rationally designed and prepared by a combination of ring-opening polymerization (ROP), chain end modification and intermolecular Cu-catalyzed azide–alkyne cycloaddition (CuAAC) “click” reaction. Firstly, cyclic PCL with two pendent alkynyl groups (c-PCL-2alkynyl) was prepared via successive ROP, a bimolecular CuAAC “click” reaction and transformation of pendent hydroxyl groups to alkynyl groups. Subsequently, a tadpole-shaped amphiphilic copolymer PEG-b-(c-PCL)-b-PEG was fabricated by the CuAAC “click” reaction between c-PCL-2alkynyl and azido-terminated PEG (PEG-N₃). For the comparison purpose, a linear triblock copolymer [PEG-b-(l-PCL)-b-PEG] and a 4-arm star copolymer (2PEG-b-2PCL) with comparable molecular weights and compositions were also synthesized. All these polymers were fully characterized by size exclusion chromatography (SEC), nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. In addition, the self-assembly behavior, drug loading capacity and in vitro cytotoxicity of the tadpole-shaped amphiphilic copolymer and its linear and 4-arm star analogues were preliminarily investigated. It was found that the assemblies of PEG-b-(c-PCL)-b-PEG showed a similar spherical morphology but a smaller size compared with those of PEG-b-(l-PCL)-b-PEG and 2PEG-b-2PCL. The in vitro cytotoxicities against L929 fibroblast cells and HeLa cells evaluated by MTT assays revealed that the copolymers, especially PEG-b-(c-PCL)-b-PEG and 2PEG-b-2PCL, exhibited favorable biocompatibility, which might be potentially used as nanoscale drug delivery systems.