Precise control of drug release from dually responsive poly(ether urethane) nanoparticles

Abstract

A series of linear poly(ether urethane)s was synthesized based on alternating PEG-diisocyanate of different molecular weight and N-methyldiethanolamine containing ternary amino moieties. The molecular structures of the obtained copolymers were confirmed with nuclear magnetic resonance, Fourier transform infrared spectroscopy and gel permeation chromatography. In aqueous solution, the amphiphilic copolymers could self-assemble into nanoparticles, which showed temperature and pH dual-responsive character. The stimuli-responsive behavior was characterized by light transmission, dynamic light scattering, nuclear magnetic resonance, and transmission electron microscopy. The phase transition temperature (T_p) of the nanoparticles could be modulated by changing the molecular weight of the PEG segments. The encapsulation and release of doxorubicin (DOX) were investigated using the obtained polymeric nanoparticles as carriers. The in vitro experimental results showed that DOX release from the nanoparticles was significantly accelerated when it was conducted at a higher temperature and lower pH value. Importantly, only when the ambient temperature was higher than the corresponding T_p, the drug release could be remarkably enhanced by the pH decrease. The system showed a temperature-triggered pH-dependent drug release. Cell viability and microscopic observation of liver cells (HepG2 cells) treated with the DOX-loaded polymeric nanoparticles demonstrated that the therapeutic activity and the DOX distribution could be precisely controlled by the novel dual-responsive system.