Dual thermo-and pH-sensitive injectable hydrogels of chitosan/(poly(N-isopropylacrylamide-co-itaconic acid)) for doxorubicin delivery in breast cancer

In this work, dual thermo- and pH-responsive hydrogels were developed and loaded with doxorubicin (DOX) with potential therapy of breast cancer. Hydrogels were engineered by blending synthesized poly(N-isopropylacrylamide-co-itaconic acid) (PNIAAm-co-IA) with chitosan (CS) through ionic crosslinking using glycerophosphate (GP). The synthesized copolymer and hydrogels were characterized by means of various techniques such as FT-IR, 1H NMR, scanning electron microscopy (SEM) and energy dispersive X-ray (EDX). Lower critical solution temperature (LCST) of the copolymer was determined around 39 °C using UV–Vis spectroscopy. Swelling studies of hydrogels and their morphology implied the porous structure, high water content with rapid swelling/deswelling rate in response to abrupt changes of pH and temperature. The release investigation of DOX at different concentration, temperature and pH values confirmed the accelerated release of DOX in lower concentration and acidic condition at 37 °C as compared to neutral pH and the temperature of 40 °C. The MTT cytotoxicity study revealed that the hydrogels are cytocompatible and exert no/negligible cytotoxicity on MCF-7 cells. The proliferation of MCF-7 cells on the prepared hydrogel and DOX-loaded hydrogel was evaluated by 4′,6-diamidino-2-phenylindole (DAPI) staining which further demonstrated the potential of developed hydrogels for local therapy of breast cancer.