Department of Orthopedics combined TCM with Western Medicine, Honghui Hospital, Xi'an Jiaotong University, No. 555 Youyi East Road, Beilin, Xi'an, Shaanxi, 710054, China.
Department of Traditional Chinese Medicine, High-Tech Hospital, Xi'an, Shaanxi, China.
J Biomater Sci Polym Ed. 2021 Jul;32(10):1288-1300. doi: 10.1080/09205063.2021.1912976. Epub 2021 May 18.
Triptolide (extract of herb ) 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 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 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.
雷公藤甲素（草药提取物）具有很强的免疫抑制作用，因此被广泛用于类风湿关节炎。市售的口服（片剂剂型）和注射用制剂作用时间短（半衰期=38 分钟），且不限于多器官毒性，这限制了雷公藤甲素在临床实践中的应用。在这项研究中，开发了一种载雷公藤甲素的 Pluronic® F68-还原氧化石墨烯经皮（非侵入性）水凝胶，以实现雷公藤甲素的持续释放。傅里叶变换红外光谱、X 射线衍射和拉曼光谱证实了 Pluronic F68-还原氧化石墨烯的合成。透射电子显微镜显示了平坦的褶皱纳米片。所开发的水凝胶表现出理想的粘度（11,261-11,365 cps）、粘性（0.25 mJ）、硬度（6.5 g）和内聚性（1.85），适合经皮应用。释放研究表明，Pluronic F68-还原氧化石墨烯水凝胶能够延长释放时间长达 14 小时（63.64-96.78%），这是由于氧化石墨烯与雷公藤甲素之间的强π-π相互作用。大鼠模型中的药代动力学参数证实，与不含还原氧化石墨烯的对照水凝胶相比，Pluronic F68-还原氧化石墨烯水凝胶可提高相对生物利用度（3.3 倍）。类风湿疗效模型表明，Pluronic F68-还原氧化石墨烯水凝胶有可能替代片剂和注射制剂，用于治疗膝关节炎类风湿（70-75%缓解）。
