Preparation and characterization of thermo-responsive amphiphilic triblock copolymer and its self-assembled micelle for controlled drug release

An amphiphilic thermo-responsive ABA triblock copolymer, poly(methyl methacrylate)-b-poly(N-isopropylacrylamide-co-poly(ethylene-glycol) methyl ether methacrlate)-b-poly(methyl methacrylate) (PMMA-b-P(NIPAM-co-PEGMEMA)-b-PMMA), was designed and synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization, and subsequently characterized by FT-IR, H-1 NMR and GPC. The copolymer can disperse in water and self-assemble into nanoscaled micelles in a "flower-like" arrangement at room temperature; the hydrophobic PMMA tucks in the core while the hydrophilic and improved biocompatible P(NIPAM-co-PEGMEMA) forms a thermosensitive outer shell. The resulting micelles were investigated using fluorescence spectroscopy, dynamic light scattering technique (DLS) and transmission electron microscopy (TEM). The copolymer exhibited a lower critical solution temperature (LCST) of around 39 degrees C via optical transmittance measurements. Notably, there was no copolymer precipitation observed at the LCST, which was propitious to in vivo use of the micelle. The micelles loaded with folic acid as a model drug showed a desired thermo-responsive drug release behavior. It was found that the rate and amount (maximum percentage 85%) of the drug release was much higher above the LCST than that (maximum percentage 36%) below the LCST. These results indicate that the thermosensitive triblock copolymer possesses promising potential applications as a "smart" drug carrier in biomedical science. (C) 2009 Elsevier B.V. All rights reserved.