Preparation, characterization, and in vitro release studies of multifunctional nanoformulations designed by functionalized graphene nanosheets with natural compounds

Abstract

The use of graphene-based nanomaterials in nanomedicine continues to expand, particularly in drug delivery nanoplatforms that provide advantages like multifunctional designs, prolonged release of drugs, cancer targeting, etc. There is a lack of data to develop graphene nanosheets for natural compounds with anticancer properties. To achieve the targeted delivery system's final objective, we prepared two different types of nanosheets: nano-sized graphene (NG) and nanosized graphene oxide (NGO). They were functionalized with PEG-NH₂ and formulated with three natural anticancer compounds: piperine (PIP), artemisinin (ART), and emodin (EMO). Finally, folic acid-conjugated enteric coating (Eudragit S100 polymer) was achieved (ES100-FA). The enteric coating changed the mean size distribution of the two materials by less than 280 nm and all nanoformulations displayed negative zeta potential. The PEG-NH₂ nanosheets demonstrated a high drug loading rate, loading capacity, and entrapment efficiency. Compared to ART nanoformulations (< 24 h), PIP and EMO-nanoformulations showed long-term sustained release throughout 96 h, according to in vitro drug release experiments. The release profiles of PIP, ART, and EMO-based nanoformulations showed a pH-dependent release effect and different release properties. This developed system showed the potential of graphene nanosheets to construct multifunctional nanoplatform and sustain the release of plant-derived natural therapeutic compounds.