One-pot synthesis of triple responsive composite hydrogel based on hyaluronic acid and its targeted controlled drug release

Owing to the complexity of tumor microenvironment, drug carriers will be required to achieve controlled targeted drug release according to different patient sites. With hyaluronic acid (HA), acrylic acid (AA), and N-isopropylacrylamide (NIPAM) as the main raw materials, a triple-responsive HA-AA-NIPAM composite hydrogel with active targeting was synthesized by one-pot method. The resulting hydrogel was characterized using Fourier infrared spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. Using doxorubicin (DOX) as a model drug, drug loading content and drug loading efficiency of the hydrogel could attain about 20.22% and 72.39%, respectively. The results demonstrated that sustained release of loaded DOX from HA-AA-NIPAM hydrogel reached approximately 84% after 6 h at pH = 2, t = 40 °C, and in the presence of HAase environment. Also, six kinetic models were used to fit the releasing data of optimal drug release environment, and the releasing behaviors of the drug-loaded hydrogel could be well described by Ritger-Peppas model with R2 of >0.99. Besides, after co-cultivation of MDA-MB-231 cell with HA-AA-NIPAM hydrogel, cell viability could maintain >90% and excellent cell adhesion was observed. Laser confocal results revealed that more pronounced green (DOX) fluorescence was displayed in HA-AA-NIPAM hydrogel compared to binary AA-NIPAM hydrogel. Therefore, HA-AA-NIPAM hydrogel was promising to be potentially used in biomedical fields to achieve targeted controlled release of chemotherapeutic drugs.