Triptolide laden reduced graphene oxide transdermal hydrogel to manage knee arthritis: in vitro and in vivo studies

The biomedical applications of graphene-based materials, including drug delivery, have grown rapidly in the past few years. Graphene and graphene oxide have been extensively explored as some of the most promising biomaterials for biomedical applications due to their unique properties: two-dimensional planar structure, large surface area, chemical and mechanical stability, superb conductivity and good biocompatibility. These properties result in promising applications for the design of advanced drug delivery systems and delivery of a broad range of therapeutics. In this review we present an overview of recent advances in this field of research. We briefly describe current methods for the surface modification of graphene-based nanocarriers, their biocompatibility and toxicity, followed by a summary of the most appealing examples demonstrated for the delivery of anti-cancer drugs and genes. Additionally, new drug delivery concepts based on controlling mechanisms, including targeting and stimulation with pH, chemical interactions, thermal, photo- and magnetic induction, are discussed. Finally the review is summarized, with a brief conclusion of future prospects and challenges in this field.

Exfoliation of graphite is a promising approach for large-scale production of graphene. Oxidation of graphite effectively facilitates the exfoliation process, yet necessitates several lengthy washing and reduction processes to convert the exfoliated graphite oxide (graphene oxide, GO) to reduced graphene oxide (RGO). Although filtration, centrifugation and dialysis have been frequently used in the washing stage, none of them is favorable for large-scale production. Here, we report the synthesis of RGO by sonication-assisted oxidation of graphite in a solution of potassium permanganate and concentrated sulfuric acid followed by reduction with ascorbic acid prior to any washing processes. GO loses its hydrophilicity during the reduction stage which facilitates the washing step and reduces the time required for production of RGO. Furthermore, simultaneous oxidation and exfoliation significantly enhance the yield of few-layer GO. We hope this one-pot and fully-scalable protocol paves the road toward out of lab applications of graphene.

Triptolide (TP), a major active and toxic ingredient isolated from the traditional Chinese herb Tripterygium wilfordii Hook f. (TWHF). A widespread application of TP raises the question on the safety of its use in clinical settings. The metabolism of TP is mediated by hepatic cytochrome P450s, and a strong correlation exists between TP toxicity and CPY3A. Toxicity of TP and the molecular mechanisms of its toxic effects have been studied in recent years. Studies have demonstrated that TP exposure results in injury of various organs, including the liver, kidney, testes, ovary, and heart in animals and even in humans, according to clinical case reports. Moreover, on the cellular level, TP has been reported to be associated with diverse toxic effects, encompassing membrane damage, mitochondrial disruption, metabolism dysfunction, endoplasmic reticulum stress, oxidative stress, apoptosis and autophagy. This review presents an overview of the current findings related to TP toxicity with an emphasis on biological targets and the molecular mechanisms that may be involved, thus providing a systematic understanding of the mechanisms by which TP affects cells and tissues in vitro and in vivo.