Novel Amphiphilic, Biodegradable, Biocompatible, Thermo-Responsive ABA Triblock Copolymers Based on PCL and PEG Analogues via a Combination of ROP and RAFT: Synthesis, Characterization, and Sustained Drug Release from Self-Assembled Micelles

Well-defined novel, linear, biodegradable, amphiphilic thermo-responsive ABA-type triblock copolymers, poly[2-(2-methoxyethoxy) ethyl methacrylate-co-oligo(ethylene glycol) methacrylate]-b-poly(ε-caprolactone)-b-poly[2-(2-methoxyethoxy) ethyl methacrylate-co-oligo(ethylene glycol) methacrylate] [P(MEO(2)MA-co-OEGMA)-b-PCL-b-P(MEO(2)MA-co-OEGMA)] (tBPs), were synthesized via a combination of ring-opening polymerization (ROP) of ε-caprolactone (εCL) and reversible addition-fragmentation chain transfer polymerization (RAFT) of MEO(2)MA and OEGMA comonomers. The chemical structures and compositions of these copolymers were characterized using Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance ((1)H NMR). The molecular weights of the copolymers were obtained using gel permeation chromatography (GPC) measurements. Thermo-responsive micelles were obtained by self-assembly of copolymers in aqueous medium. The temperature sensitivity and micelllization behavior of amphiphilic triblock copolymers solutions were studied by transmittance, fluorescence probe, surface tension, dynamic light scattering (DLS) and transmission electron microscopy (TEM). A hydrophobic drug, anethole, was encapsulated in micelles by using the dialysis method. The average particle sizes of drug-loaded micelles were determined by dynamic light scattering measurement. In vitro, the sustained release of the anethole was performed in pH 7.4 phosphate-buffered saline (PBS) at different temperatures. Results showed that the triblock copolymer’s micelles were quite effective in the encapsulation and controlled release of anethole. The vial inversion test demonstrated that the triblock copolymers could trigger the sol-gel transition which also depended on the temperature, and its sol-gel transition temperature gradually decreased with increasing concentration. The hydrogel system could also be used as a carrier of hydrophobic drugs in medicine.