Abstract
Injectable hydrogel is a novel smart material which can undergo sol-gel phase transition by the stimulation of physiological factors or environmental stimuli. In the field of pharmaceutics, it can be used as a drug carrier that can control the drug release rate by the alteration of physiological environment; in the field of tissue engineering, it can be applied as a scaffold that can be implanted into the defect site by the method of injection. Pluronic F127 is a smart polymer which has the property of sol-gel in transition response to temperature but was limited by the weak mechanical strength. Hyaluronic acid is a linear natural polymer composed of repeating disaccharides found in the extracellular matrix and broadly applied in the field of cosmetology, health food, and medicine. The purpose of this study is to develop a thermosensitive hydrogel composed of Pluronic F127 and hyaluronic acid with improved mechanical stability and biocompatibility as a controlled drug delivery carrier for cancer therapy. The results showed that the introduction of hexamethylene diisocyanate (HDI) as the extender for Pluronic F127 polymer chains made the micelles more stable. Furthermore, HDI-Pluronic F127 still maintained sol-gel transition property with broader temperature range and the critical gelation concentration was also decreased. The cell viability test showed the HDI-Pluronic F127/ hyaluronic acid hydrogel had favorable biocompatibility. With appropriate physical and chemical properties of this thermosensitive hydrogel, anticancer drugs such as doxorubicin and paclitaxol were incorporated to investigate the drug release profile and anticancer treatment effect. The results showed that the slow controlled release of anticancer drugs can be achieved over one month and significantly inhibit the proliferation of human breast tumor cells. By adjusting the concentration of hydrogels, the release profile can also be manipulated if desired. In brief, the HDI-Pluronic F127/hyaluronic acid composite hydrogel prepared in this study can maintain solution form at low temperature and become gelation as the temperature increase to body temperature. It was found that the hydrogel was biocompatible and had the slow release property for anticancer drugs. Therefore, the HDI-Pluronic F127/hyaluronic acid hydrogel has considerable potential applications in the field of controlled drug delivery in the future.