The effect of salt and pH on the phase-transition behaviors of temperature-sensitive copolymers based on N-isopropylacrylamide.

The salt and pH effects on the phase transition behaviors of temperature-sensitive hydrophilic and amphiphilic polymers containing copolymers of N-isopropylacrylamide as hydrophilic segments were investigated by UV and dynamic light scattering studies. The polymers used for this study include two hydrophilic polymers of HO-terminated poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (1) and HO-functionalized poly(N-isopropylacrylamide-co-N-hydroxylmethylacrylamide) (3), and their amphiphilic derivatives of poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-poly(D,L-lactide) (2) and cholesteryl-grafted poly(N-isopropylacrylamide-co-N-hydroxylmethylacrylamide) (4). With the increase of NaCl concentration, significant salt effects on their phase transition behaviors were observed. (1) Significant decreases in the lower critical solution temperatures of all polymers were observed, the salt effects were also characterized by a newly defined 'phase transition salt concentration'; (2) time-course UV spectroscopic studies showed that the phase transitions became faster and more complete with the increase of NaCl concentration, which were demonstrated by a newly defined 'phase transition constant'; (3) the salt exerted stronger effects on phase transition behaviors of the amphiphilic polymers than that of the hydrophilic polymers, and on polymer 4 than polymer 2. In contrast, the phase transition behaviors of the polymers were less sensitive to pH. The present studies provide important information for the design and synthesis of temperature-sensitive polymers and polymeric micelles that are important drug delivery carriers for hydrophobic drugs.