Molecular insight into the role of polyethylene glycol and cholesterol on the performance of graphene-based nanomaterials in Blood-brain barrier delivery

Abstract In this study, the efficacy of polyethylene glycol-functionalized graphene oxide (GO-PEG) and reduced graphene oxide (RGO-PEG) in the uptake and release of temozolomide (TMZ) is investigated. Also, the effect of cholesterol (CHL) on these processes is explored. Two different configurations of TMZ and CHL on top of the carriers are studied through density functional theory (DFT) calculations. The obtained results show that the adsorption of TMZ and CHL molecules on GO-PEG and RGO-PEG is exergonic. The interaction of cholesterol with GO-PEG and RGO-PEG is stronger than TMZ, which can facilitate drug release. It is found that the van der Waals forces are the predominant interaction in the stability of all studied configurations, which in the most stable complexes, accompanied by the formation of intermolecular hydrogen bonds. A series of molecular dynamics (MD) simulations are performed to explore the competition of GO-PEG and RGO-PEG in the adsorption of the temozolomide drug molecule. The obtained results illustrated that the RGO-PEG had a greater capacity to adsorb TMZ. Moreover, with using MD simulation release of TMZ from the carriers in the presence of CHL is also examined. The results indicated that RGO-PEG had better behavior in drug release than GO-PEG.