Dual-responsive polymer-drug nanoparticles for drug delivery

A well-defined, dual temperature- and pH-responsive drug carrier was synthesized through the radical copolymerization of methacrylic acid, N-isopropylacrylamide, and an N-(methacryloyl)glycylglycine 4-nitrophenyl ester. When the anticancer agent gemcitabine or antibiotic sulfamethoxazole was conjugated with a polymer and heated beyond its low critical solution temperature (40 °C), a dual temperature- and pH-induced phase transition was observed. This temperature was considered ideal for activating drug aggregation under hyperthermic and acidic conditions. The structure and properties of polymer drugs were investigated using nuclear magnetic resonance, Fourier transform infrared spectrometry, ultraviolet-visible absorption, transmission electron microscopy, and gel permeation chromatography. At a critical micelle concentration of 1 mg/mL, both polymer drugs formed micellar structures with diameters ranging from 50 nm to 150 nm, based on TEM image. These micelles exhibited higher pharmacological efficacy than the free drug alone did, and the cytotoxicity at the target site was substantially enhanced compared with that of the polymer-drug conjugate formed under normal physiological conditions.