ABC triblock copolymers with pH-responsive LCST for controlled drug delivery

The thermo- and amphiphilic ABC triblock copolymers, single-methoxypoly(ethylene glycol)-b-poly(N-isopropylacrylamide-co-acrylic acid)-b-poly(methyl methacrylate), were synthesized by reversible addition fragmentation chain transfer radical polymerization. The triblock copolymers were characterized by Fourier transform infrared spectroscopy, ¹ H-NMR, and gel permeation chromatography. The copolymers self-assemble into thermo-responsive nano-sized micelles in aqueous media. Transmission electron microscopy and dynamic light scattering showed that the micelles were regularly spherical in shape with an average diameter ~120 nm. Fluorescence analysis indicated that the triblock copolymer had a low critical micelle concentration of 2.5 mg/L in aqueous media at pH 7.4 and room temperature. The lower critical solution temperature (LCST) of the micelles could be altered by simply changing the pH. The LCST of the triblock copolymer at pH 5.5 was altered to 37.5 ^° C (close to physiological temperature) by copolymerizing N-isopropylacrylamide with acrylic acid. When the pH was increased to 7.4, the LCST increased to 55 ^° C and it decreased to 33 ^° C when the pH was 2.0. The micelles exhibited good biocompatibility with human embryonic kidney cells, when the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was performed. The controlled release of folic acid (FA) from FA-loaded micelles under different conditions was evaluated. The rate and amount of the drug released were greater above the LCST than below it.