Injectable and Thermoresponsive Self-Assembled Nanocomposite Hydrogel for Long-Term Anticancer Drug Delivery

Abstract

The purpose of this study is to develop an injectable thermoresponsive hydrogel system that can undergo sol-gel phase transition by the stimulation of body temperature with improved mechanical stability and biocompatibility as a controlled drug delivery carrier for cancer therapy. Hexamethylene diisocyanate (HDI) was introduced into Pluronic F127 as a chain extender to improve the mechanical stability. HDI-Pluronic F127 copolymer was then incorporated with hyaluronic acid to develop a thermoresponsive nanocomposite hydrogel system. The physiochemical properties were characterized. The anticancer drug release profile and effect to inhibit tumor cells growth were analyzed in vitro and in vivo. The results showed that HDI-Pluronic F127/hyaluronic acid thermoresponsive hydrogel could undergo sol-gel transition as temperature increased to 37 °C. The nanocomposite polymer can spontaneously self-assemble into micellar structure with size of 100-200 nm. The release of doxorubicin (DOX) from HDI-PF127/HA composite hydrogel was a zero-order profile and maintained sustained release for over 28 days. The viability of tumor cells and size of tumor significantly decreased with incubation time, indicating the potential to have a therapeutic effect for cancer therapy. The injectable thermoresponsive nanocomposite hydrogel system was biocompatible and degradable and had the slow controlled release property for anticancer drugs with potential applications in the field of drug delivery.