Thermoresponsive random poly(ether urethanes) with tailorable LCSTs for anticancer drug delivery

Abstract

A new class of thermoresponsive random polyurethanes is successfully synthesized and characterized. Poly(ethylene glycol) diol (Mn = 1500 Da) and 2,2-dimethylolpropionic acid are reacted with isophorone diisocyanate in the presence of methane sulfonic acid catalyst. It is found that these polyurethanes are thermoresponsive in aqueous media and manifest a lower critical solution temperature (LCST) that can be easily tuned from 30 °C to 70 °C by increasing the poly(ethylene glycol) content. Their sharp LCST transitions make these random polyurethanes ideal candidates for stimuli-responsive drug delivery applications. To that end, the ability of these systems to efficiently sequester doxorubicin (up to 36 wt%) by means of a sonication/dialysis method is successfully demonstrated. Additionally, it is also demonstrated that accelerated doxorubicin release kinetics from the nanoparticles can be attained above the LCST. A new class of thermoresponsive random polyurethanes is synthesized through organocatalytic polymerization. The lower critical solution temperatures (LCSTs) of the polymers are easily tuned from 30 to 70 °C by increasing the poly(ethylene glycol) content. Acid groups in the polymers allow effective loading of amine-containing anticancer drugs, and drug release is accelerated when the temperature increases above the LCST.