Preparation and Optimization of PEGylated Nano Graphene Oxide-Based Delivery System for Drugs with Different Molecular Structures Using Design of Experiment (DoE)

Abstract

Graphene oxide (GO), due to its 2D planar structure and favorable physical and chemical properties, has been used in different fields including drug delivery. This study aimed to investigate the impact of different process parameters on the average size of drug-loaded PEGylated nano graphene oxide (NGO-PEG) particles using design of experiment (DoE) and the loading of drugs with different molecular structures on an NGO-PEG-based delivery system. GO was prepared from graphite, processed using a sonication method, and functionalized using PEG 6000. Acetaminophen (AMP), diclofenac (DIC), and methotrexate (MTX) were loaded onto NGO-PEG particles. Drug-loaded NGO-PEG was then characterized using dynamic light scattering (DLS), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), XRD. The DLS data showed that the drug-loaded NGO-PEG suspensions were in the size range of 200 nm–1.3 µm. The sonication time and the stirring rate were found to be the major process parameters which affected the average size of the drug-loaded NGO-PEG. FTIR, DSC, XRD, and SEM demonstrated that the functionalization or coating of the NGO occurred through physical interaction using PEG 6000. Methotrexate (MTX), with the highest number of aromatic rings, showed the highest loading efficiency of 95.6% compared to drugs with fewer aromatic rings (diclofenac (DIC) 70.5% and acetaminophen (AMP) 65.5%). This study suggests that GO-based nano delivery systems can be used to deliver drugs with multiple aromatic rings with a low water solubility and targeted delivery (e.g., cancer).

Characteristics of Graphene Oxide for Gene Transfection and Controlled Release in Breast Cancer Cells

“…Despite its optical properties and large surface area, the hydrophobic nature of graphene has caused aggregations that have hindered its functionality in solution-processed applications. In order to overcome this limitation, the synthesis of GO and reduced GO (rGO) was introduced and has improved the solubility and processability of graphene-based materials [ 21 , 22 ]. In comparison with other carbon-based materials, GO has a large surface area with theoretical and measured values of around 2418 and 2391 m 2 /g, respectively [ 23 ], an order of magnitude more than that of the majority of other nanomaterials [ 24 ].…”

“…The synthesis of GO has developed over the years [ 26 , 27 , 28 ] after the original protocol was proposed [ 29 ]. Recently, the modified Hummers method has been used to produce exfoliated graphene oxide flakes with the potential for additional modification in biomedical applications [ 22 , 25 , 28 , 30 , 31 ]. As a result, graphene is highly oxidized, leaving hydroxyl and epoxy functional groups on the planar surface, while the carboxylic groups are found at the edges [ 32 ].…”

Design Strategies of Tumor‐Targeted Delivery Systems Based on 2D Nanomaterials

“…[31] Some other examples of surface modification of 2D NMs using PEG are shown in Table 1. [165][166][167][168][169][170][171][172][173] PEG modification can effectively improve the half-life of drug delivery vectors, increase biocompatibility, and improve the effective accumulation of drug delivery vectors at tumor sites, thus enhancing treatment efficacy.…”

“…The MTX with the highest number of aromatic rings had the highest drug delivery efficiency, which was 95.6%, while the drugs with fewer aromatic rings were DIC (70.5%), AMP (65.5%). [169] 2D PEG-PLA-graphene loading anticancer drug paclitaxel…”

Development of Stable Liposomal Drug Delivery System of Thymoquinone and Its In Vitro Anticancer Studies Using Breast Cancer and Cervical Cancer Cell Lines

“…Nano-drug-delivery systems can deliver drug to the specific site of action and provide better efficacy with fewer side effects [ 3 ]. Nanotechnology allows atomic- and molecular-level fabrication which helps in designing, optimizing, producing, and characterizing nanocarriers [ 4 , 5 ]. The small sizes of nanocarriers make them unique as potential agents for biomedical applications [ 1 , 3 , 4 , 6 ].…”