Chitosan/agarose/graphene oxide nanohydrogel as drug delivery system of 5-fluorouracil in breast cancer therapy

Breast cancer refers to a very common deadly class of malignant tumors, especially in women worldwide. In the present study, a promising methodology has been developed to simultaneously improve the drug loading performance and achieve a sustained release of 5-fluorouracil (5-FU) as a model drug for breast cancer. For this purpose, a pH-sensitive and biocompatible hydrogel of chitosan/agarose/graphene oxide (CS/AG/GO) was first synthesized with glyoxal as cross-linker. 5-FU-loaded nanocomposites (NCs) of CS/AG/GO were then prepared via water-in-oil-in-water (W/O/W) emulsification technique. XRD and FTIR analyses confirmed the successful synthesis of the nanocarriers and gave insight on their crystalline structure and molecular interactions between the components. DLS demonstrated that the nanocarriers comprise nanoparticles with an average size of 197 nm and a PDI of 0.34. SEM revealed their spherical morphology and zeta potential measurements indicated an average surface charge of +23.5 mV. The drug loading and entrapment efficiencies (57% and 92%, respectively) were significantly higher than those reported previously for other nanocarriers. A very effective and sustained drug release profile was observed at pH 5.4; in 48 h, almost the entire 5-FU content was released. Moreover, effective cytotoxicity against breast cancer cell (BCC) lines (MCF-7) was observed: the cell viability upon incubation with CS/AG/GO/5-FU was about 23%, demonstrating its anti-cancer capability. Therefore, the synthesized NCs can potentially act as pH-sensitive nanovehicles for programmed release of 5-FU in breast cancer treatment.