Nanocarriers for drug-delivery systems using a ureido-derivatized polymer gatekeeper for temperature-controlled spatiotemporal on-off drug release.

Abstract

Accidental chemotherapy extravasation exacerbates the side effects of anticancer drugs. Therefore, drug-delivery nanocarriers should be designed to avoid persistent drug release at off-target sites and promote burst drug release at on-target. Considering these requirements, poly(allylamine)-co-poly(allylurea) (PAU), a ureido-derivatized temperature responsive polymer with upper critical solution temperature (UCSTs), is an ideal material. This report describes the fabrication, characterization, and in vitro cellular toxicity of PAU polymer-grafted magnetic mesoporous silica nanoparticles as drug-delivery nanocarriers. A UCST of 43°C and an ultranarrow transition temperature range of 39-43°C was realized, ensuring that the nanocarriers suppressed undesirable leakage to below 10% of the drug loading for 8h in the absence of a thermal stimulus. A drug release burst of up to 75% of the drug loading was achieved within 30min after the stimulus, reducing the viability of the in vitro cancer cells to 12%. Therefore, the ureido-derivatized polymer is one of the most suitable gatekeepers for drug-delivery nanocarriers.