PEGylated Graphene Oxide as a Nanodrug Delivery Vehicle for Podophyllotoxin (GO/PEG/PTOX) and In Vitro -Amylase/-Glucosidase Inhibition Activities

This study aims to develop a nanodrug delivery systemcontainingpodophyllotoxin (PTOX), a known anticancer drug, loaded on grapheneoxide (GO). The system's ability to inhibit alpha-amylaseand alpha-glucosidase enzymes was also investigated. PTOX was isolatedfrom Podophyllum hexandrum roots witha yield of 2.3%. GO, prepared by Hummer's method, was convertedinto GO-COOH and surface-mobilized using polyethylene glycol (PEG)(1:1) in an aqueous medium to obtain GO-PEG. PTOX was loaded on GO-PEGin a facile manner with a 25% loading ratio. All the samples werecharacterized using FT-IR spectroscopy, UV/visible spectroscopy, andscanning electron microscopy (SEM). In FT-IR spectral data, GO-PEG-PTOXexhibited a reduction in acidic functionalities and there was an appearanceof the ester linkage of PTOX with GO. The UV/visible measurementssuggested an increase of absorbance in 290-350 nm regions forGO-PEG, suggesting the successful drug loading on its surface (25%).GO-PEG-PTOX exhibited a rough, aggregated, and scattered type of patternin SEM with distinct edges and binding of PTOX on its surface. GO-PEG-PTOXremained potent in inhibiting both alpha-amylase and alpha-glucosidasewith IC50 values of 7 and 5 mg/mL, closer to the IC50 of pure PTOX (5 and 4.5 mg/mL), respectively. Owing to the25% loading ratio and 50% release within 48 h, our results are muchmore promising. Additionally, the molecular docking studies confirmedfour types of interactions between the active centers of enzymes andPTOX, thus supporting the experimental results. In conclusion, thePTOX-loaded GO nanocomposites are promising alpha-amylase- and alpha-glucosidase-inhibitoryagents when applied in vitro and have been reportedfor the first time.