High encapsulation and localized delivery of curcumin from an injectable hydrogel

Abstract

Most chemotherapy currently available for cancer treatment has limited potential to successful clinical cancer therapy, mainly due to low encapsulating capacity of drugs and unavailable pharmacologically beneficial concentrations at the tumor site. Herein, a novel yet simple strategy is developed to enhance drug encapsulating capacity and localized drug concentration using an injectable hydrogel based on thiolated chitosan (TCS) and poly(ethylene glycol) diacrylate (PEGDA). Almost 100% of encapsulating capacity is achieved when anti-cancer drug curcumin is encapsulated in the system. The interaction of curcumin with PEGDA is determined by fluorescence spectroscopy and the binding constant is calculated, followed by a simulation by a docking study using AutoDock. To improve the anti-tumor activity and achieve effective local concentrations, lysozyme is introduced into the system. Sustained curcumin release in a controlled lysozyme-responsive behaviour is observed, which enables the drug concentration to reach the therapeutic threshold promptly. The system displays efficient intracellular curcumin release to promote cancer cells apoptosis in vitro. In addition, the system effectively delays the tumor growth and reduces adverse effects in tumor-bearing nude mice. The strategy of localized, high encapsulation of drug by using an injectable hydrogel would be particularly beneficial with many insoluble anti-cancer drugs.