▎ 摘　　要

Ankylosing spondylitis is an inflammatory arthritic disease affecting the spine and large joints, causing severe pain. Flurbiprofen is widely used as an oral formulation (tablet dosage form) to control pain in spondylitis; however, owing to its short half-life (3.9 h), need for frequent dosing (four times daily), and abdominal discomfort, patient compliance remains extremely poor. In the present study, a flurbiprofen-loaded reduced graphene oxide transdermal (non-invasive) hydrogel was developed to improve drug permeation and achieve sustained drug release for pain management. Fourier transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy confirmed the synthesis of polyoxypropylene-polyoxyethylene block copolymer stabilized reduced graphene oxide. Transmission electron microscopy images presented flat, wrinkled nanosheets of reduced graphene oxide. The developed hydrogel showed desirable viscosity, pH, drug content, adhesiveness, hardness, and cohesiveness (texture profile) for transdermal application. The ex vivo permeability studies revealed the ability of the reduced graphene oxide hydrogel to increase drug permeation and release (sustained release) for up to 72 h owing to strong pi-pi interactions, as well as pi-sigma and pi-hydrogen bonds between flurbiprofen and reduced graphene oxide. In the rat model, in vivo pharmacokinetic parameters confirmed the improved relative bioavailability of reduced graphene oxide hydrogel when compared with the control hydrogel (without reduced graphene oxide) and marketed transdermal patch. The analgesic and anti-inflammatory assessments in rat models confirmed the ability of the flurbiprofen-reduced graphene oxide hydrogel to manage pain in various diseases, such as ankylosing spondylitis, to substitute tablets and parenteral injections, compared with the marketed transdermal patch.