Functionalized PEGylated graphene oxide with folic acid and hydrazine as a new pH-responsive nanocarrier for doxorubicin delivery

In this study, a novel pH-responsive nanocarrier composed of PEGylated graphene oxide functionalized with folic acid and hydrazine was developed for the targeted delivery and sustained release of doxorubicin. The prepared nanocarrier was characterized using various techniques, including scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, transmission electron microscopy, and dynamic light scattering. These analyses provided evidence of the successful PEGylation of graphene oxide and functionalization with hydrazine and folic acid. The effects of different factors, such as contact time, temperature, and initial drug concentration, were studied using response surface methodology based on the Box-Behnken design. Seventeen runs were performed and the optimal conditions for drug loading were observed at a contact time of 3.77 h, temperature of 35 degrees C, and initial drug concentration of 617 mg/L. The maximum drug-loading efficiency under optimal conditions was 95.86%. The validity of the optimum factors for drug-loading efficiency was studied using analysis of variance. An in vitro drug release study demonstrated that 99.82% of doxorubicin was released in simulated cancer cells, whereas only 15.36% was released in a simulated environment that resembled physiological conditions. These results confirmed the pH-responsive nature of the nanocarrier, where the drug was released more efficiently under acidic conditions resembling cancer cells. Doxorubicin release experiments in physiological and acidic fluids proposed the Higuchi kinetic model for nanocarriers. In addition, fitting of the kinetic results to pharmacokinetic models showed non-Fickian diffusion from the nanocarrier.