An ionic hydrogel with stimuli-responsive, self-healable and injectable characteristics for the targeted and sustained delivery of doxorubicin in the treatment of breast cancer

Abstract

Designing stimuli-responsive therapeutic scaffolds to deliver hydrophobic chemo drugs with controlled and sustained release at the tumor site would be promising in cancer treatment. In a quest for the stimuli-responsive drug delivery system with sustained release, herein we have fabricated an 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-responsive properties. Further, the smart hybrid ionic hydrogel was constructed through encapsulating doxorubicin (DOX) within the 3D matrix of the ionic hydrogel, which response to intracellular biological stimuli (e.g., pH and temperature) and releases DOX in 57 h. Experimental results of IL–IL and IL–DOX interactions are supported through Density Functional Theory (DFT) calculations. In vitro cellular studies revealed that the 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.