GRAPHENE OXIDE-THIOLATED QUATERNIZED CHITOSAN AS ANTICANCER DRUG DELIVERY CARRIERS

Abstract

The objective of this research is to improve mucoadhesive properties of graphene oxide composites for anticancer drug delivery in order to extend its period time in gastrointestinal tract. The graphene oxide-thiolated quaternized chitosan (G-TQCS) as anticancer drug delivery carrier was synthesized by covalent attachment of graphene oxide (GO) with thiolated quaternized chitosan (TQCS) via amidation process and characterized by FTIR, TGA, SEM and AFM. The mucoadhesion of G-TQCS was measured by the Periodic Acid Schiff (PAS) and studied in simulated gastric tract (pH 1.2, 4.0 and 6.4). The results showed mucoadhesive property of GO and TQCS significantly higher than pure chitosan (CS) at all three pH environment. At pH 1.2, G-TQCS displayed a 10.67 and 1.45-fold stronger mucoadhesion than CS and TQCS, respectively. On the other hand, at pH 4.0 and 6.4 the mucoadhesion of G-TQCS were decreased due to the intra-attractive force between thiol and epoxy group immobilized on GO sheet, hindering the adsorption on mucin. Additionally, curcumin (Cur) using as a model natural anticancer drug for anticancer drug carrier of G-TQCS were investigated. The drug-loaded composite film (G-TQCS-Cur) was characterized by FTIR, AFM. Entrapment efficiency, in vitro drug release behavior and cytotoxicity (CHAGO and SW620 cell lines) were also studied. The obtained composite film of Cur loaded in G-TQCS not only exhibited over 90% drug entrapment efficiency but also prolonged release of Cur for up to 12 h. Moreover, G-TQCS-Cur showed higher cytotoxicity than pure Cur against cancer cell lines, especially SW620 cells when increase incubation time. After 72 h incrubation decreased IC50 value decreased from 1.07± 0.03 µg/mL of pure Cur to 0.80± 0.02 µg/mL of G-TQCS-Cur. Therefore, G-TQCS is an attractive novel composite as an anticancer drug delivery carrier for biomedical application, especially at acidic environment.