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

Triptolide (extract of herb Tripterygium wilfordii) is widely used in rheumatoid arthritis due to its potent immunosuppressant effect. The marketed oral (tablet dosage forms) and parenteral injections have short duration of action (half-life = 38 min) and not limited to multiorgan toxicity, which restrict the use of triptolide in clinical practice. In this study, a triptolide-loaded Pluronic® F68-reduced graphene oxide transdermal (non-invasive) hydrogel was developed to achieve sustained release of triptolide. Fourier transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy confirmed the synthesis of Pluronic^® F68-reduced graphene oxide. Transmission electron microscopy showed flat wrinkled-nanosheets. The developed hydrogel showed desirable viscosity (11,261-11,365 cps), adhesiveness (0.25 mJ), hardness (6.5 g), and cohesiveness (1.85) for transdermal application. The ex vivo release study demonstrated the ability of the Pluronic^® F68-reduced graphene oxide hydrogel to prolong release up to 14 h (63.64-96.78%), owing to the strong π-π interactions between the graphene oxide and the triptolide. The in vivo pharmacokinetic parameters in the rat model confirmed the improvement in the relative bioavailability (3.3-fold) with Pluronic^® F68-reduced graphene oxide hydrogel in comparison to the control hydrogel without reduced graphene oxide. The anti-rheumatoid efficacy model suggest the potential application of Pluronic^® F68-reduced graphene oxide hydrogel to treat knee rheumatoid arthritis (70-75% resolution) to substitute tablets and parenteral injections.