Ionic Hydrogel with Stimuli-Responsive, Self-healable and Injectable Characteristics for the Targeted and Sustained Delivery of Doxorubicin in the Treatment of Breast Cancer

Designing stimuli-responsive therapeutic scaffolds to deliver hydrophobic chemo drugs with controlled and sustained release at the tumour site would be promising in cancer treatment. In a quest for the stimuli-responsive drug delivery system with sustained release, herein we have fabricated active pharmaceutical ingredient based ionic liquid (IL) based hydrogel with self-healable and injectable properties. The ionic hydrogel makes a localized, long-term co-delivery system with self-healable, injectable, and stimuli-responsiveness. Further, the smart hybrid ionic hydrogel was constructed through encapsulating doxorubicin (DOX) within the 3D matrix of the ionic hydrogel, which responds to an intracellular biological stimulus (e.g., pH and temperature) and releases the DOX in 57 h. Experimental results of IL-IL, IL-DOX interactions are supported through Density Functional Theory (DFT) calculations. In vitro cellular studies revealed that DOX loaded hybrid ionic hydrogel shows a synergistic anticancer effect against MCF-07 cells. These results demonstrate the ability of the ionic hydrogel as a promising candidate for local cancer therapeutics.