Preparation and characterization of a novel thermosensitive nanoparticle for drug delivery in combined hyperthermia and chemotherapy

Abstract

In the present research, a novel thermal sensitive amphiphilic polymer was synthesized by modification of chitosan with hydrophilic hydroxybutyl groups and hydrophobic deoxycholic acid moieties. By finetuning the hydrophobic/hydrophilic balance of deoxycholic acid decorated hydroxybutyl chitosan (DAHBC), the lower critical solution temperature (LCST) of this novel polymer could be adjusted to 38.2 °C, which is an appropriate temperature in hyperthermia therapy. The polymer could self-assemble into approximately spherical nanoparticles in aqueous solutions with an average diameter of 399.6 nm and a zeta potential value of −33.8 mV. The controlled release properties of the thermosensitive drug delivery system were evaluated by using doxorubicin (DOX) as a model drug. Compared with the drug release behavior at a temperature below the LCST, the release of doxorubicin was significantly accelerated when the nanoparticles were in an environmental temperature above the LCST of the polymer. According to the results of MTT assays, blank DAHBC nanoparticles showed no significant toxicity on mouse embryo fibroblasts at a concentration as high as 1 mg ml⁻¹, and DOX-loaded nanocarriers exhibited an improved drug uptake by MCF-7 cells with the incubation temperature rising from 37 °C to 43 °C, which indicated that thermoresponsive and biocompatible DAHBC nanoparticles might have practical applications as drug carriers in combined hyperthermia and chemotherapy.