Synthesis of oxidized carboxymethyl cellulose/chitosan hydrogels doped with graphene oxide for pH- and NIR-responsive drug delivery

Biological macromolecules hydrogels are synthesized via the Schiff base reaction between oxidized carboxymethyl cellulose (oxCMC) and chitosan (CS), and graphene oxide (GO) and 5-fluorouracil (5-FU) are co-doped in the oxCMC/CS hydrogels during the cross-linking process. The acylhydrazone bonds (–HC = N–) between oxCMC and CS can be easily hydrolyzed in acidic solutions, leading to the swelling of the hydrogels and facilitated delivery of 5-FU. On the other hand, the doped GO is a promising photothermal agent, and the delivery of 5-FU can also be facilitated by the generated hyperthermia upon near infrared (NIR) irradiation. Therefore, pH- and NIR-responsive delivery of 5-FU from the hydrogels can be achieved. The kinetics of drug delivery indicate that the delivery of 5-FU from the hydrogels is controlled by first-order model. The drug-free carrier (oxCMC/CS/GO) has excellent biocompatibility while the developed drug delivery system (oxCMC/CS/GO/5-FU) exhibits high cytotoxicity against human hepatoma SMMC-7721 cells.