A novel intracellular pH-responsive formulation for FTY720 based on PEGylated graphene oxide nano-sheets.

Objective: This study was performed to investigate a novel pH-responsive nanocarrier based on modified nano graphene oxide (nGO) to promote the acid-triggered intracellular release of a poorly soluble drug, FTY720.

Methods: To synthesize a drug conjugated to modified nGO, first the polyethylene glycol (PEG) was conjugated to nGO, then the produced PEG-nGO was functionalized with the anticancer drug, FTY720, through amide bonding. It was characterized by the scanning electron microscopy (SEM), the atomic force microscopy (AFM), the Fourier transform infrared (FTIR) spectroscopy and the UV-vis spectroscopy. In vitro drug release of the FTY720-conjugated PEG-nGO was evaluated at pH 7.4 and 4.6 PBS at 37 °C. Furthermore, the antineoplastic action of unloaded and drug-loaded carrier against the human breast adenocarcinoma cell line MCF7 was explored using MTT and BrdU assays.

Results: Characterization methods indicated successful drug deposition on the surface of nGO. In vitro, drug release results revealed a significantly faster release of FTY720 from PEG-nGO at acidic pH, compared with physiological pH. The proliferation assays proved that the unloaded nGO had no significant cytotoxicity against MCF7 cells, while free FTY720- and FTY720-loaded PEG-nGO had an approximately equal cytotoxic effect on the MCF7 cells. It was found that the extended release characteristic of FTY720 was well fitted to Korsmeyer-Peppas model and the release profile of FTY720 from PEG-nGO is diffusion controlled.

Conclusion: PEGylated GO can act as a pH-responsive drug carrier to improve the efficacy of anticancer drug delivery.