Injectable hyaluronic acid–cyclodextrin-based hydrogels for localized and sustained release of anticancer drugs

Chemotherapy is the most popular anti-cancer therapy; however, it usually leads to severe side effects to healthy organs because of its high cytotoxicity and poor lesion selectivity. Although various smart carriers have been developed to provide beneficial properties for the local delivery of chemotherapy, it remains challenges in the efficiency and sustained release of drugs. Injectable hydrogels are more advantageous over other drug delivery systems owing to their unique properties, such as non-invasive administration, easy drug loading and locally controlled release at the target sites. Herein, “click” reaction between thiolated hyaluronic (HA–SH) and cyclodextrin–vinyl sulfone (CD–VS) has been used to formulate an injectable hydrogel system for the local delivery of an anticancer drug (Doxorubicin) to cancer cells. This strategy can rapidly induce hydrogelation, while increasing the loading, retention, and sustained release of DOX at the tumor sites through the formation of inclusion complexes between drugs and cyclodextrin. The physico-chemical features of hydrogels, such as gelation time, swelling ratio, porosity, and degradation rate were investigated by varying the concentrations of CD–VS crosslinker. The sustained and pH-sensitive release of DOX from hydrogels were also examined. Finally, the cell viability of the blank hydrogel, free DOX, and DOX-loaded hydrogel was studied by WST-1 and live/dead assay on HELA cells, which exhibited excellent biocompatibility of blank hydrogel and a dose-dependent cytotoxicity of DOX-loaded hydrogels. Therefore, this HA-based hydrogel will be a potential injectable carrier for the targeted and sustained delivery of chemotherapy drugs in cancer treatment.

Graphical abstract