Temperature-triggered redox-degradable poly(ether urethane) nanoparticles for controlled drug delivery

Abstract

A series of biodegradable poly(ether urethane)s that responded to changes in temperature and redox potential was synthesized via a facile one-pot method. The amphiphilic poly(ether urethane)s were comprised of 2,2′-dithiodiethanol, hydrophobic hexamethylene diisocyanate and hydrophilic poly(ethylene glycol) (PEG) segments. The phase transition temperature (T_p) of the prepared poly(ether urethane)s in aqueous solution could be easily controlled by changing the length of the PEG segment or the ratio of PEG to 2,2′-dithiodiethanol and it could be used to trigger the redox-degradable behavior. The redox-responsive disulfide bonds in the polymers could be cleaved in the presence of glutathione (GSH) when the temperature was above T_p, while the degradation was inhibited below T_p. The doxorubicin (DOX)-loaded poly(ether urethane) nanoparticles were prepared in order to investigate their stimuli-responsive release. These nanoparticles also showed a temperature-triggered redox-degradable release profile. Toxicity tests showed that the blank nanoparticles had no toxicity, whereas the DOX-loaded nanoparticles showed high cytotoxicity for liver hepatocellular cells (HepG2). Microscopic observations also revealed that the DOX molecules within the poly(ether urethane) nanoparticles could be released into HepG2 cells in the presence of higher temperature and GSH.