Morphology and drug release behavior of N-isopropylacrylamide/acrylic acid copolymer as stimuli-responsive nanogels

Abstract

Thermo- and pH-responsive N-isopropylacrylamide (NIPAM) nanogels can be obtained by copolymerization of acrylic acid (AA) comonomer through differential microemulsion polymerization. The effects of comonomer, cross-linker, surfactant contents, and water/oil ratio were preliminarily investigated by a 24 full factorial design in order to eliminate the insignificant parameters from the polymerization analysis. The smallest poly(NIPAM-co-AA) nanogel particles were 40 ± 1 nm in diameter with 6 wt% of solid content and 98% conversion without coagulation. The comonomer amounts controlled the morphologies and LCST of the poly(NIPAM-co-AA) nanogels. The hairy microgels of poly(NIPAM-co-AA) with a 10:90 mol ratio of AA/ NIPAM had a lower critical solution temperature (LCST) of 6 °C. With an increase in the AA amount to a 17 mol ratio, the LCST increased to 27 °C, resulting in core-shell morphology. The morphology of resultant nanogels was characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, and differential scanning calorimetry. Nuclear magnetic resonance spectroscopy was used to calculate the mole ratio of NIPAM and AA in resultant nanogels after dialysis. Both nanogel mole ratio and morphology effectively retained the cationic anti-cancer drug of methylene blue for several hours, an important basic requirement for a drug delivery system. Compared to core-shell microgels, a higher methylene blue release was obtained from the hairy microgels in simulated intestinal fluid.