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雷公藤甲素负载还原氧化石墨烯经皮水凝胶治疗膝关节炎:体内外研究。

Triptolide laden reduced graphene oxide transdermal hydrogel to manage knee arthritis: and studies.

机构信息

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.

出版信息

J Biomater Sci Polym Ed. 2021 Jul;32(10):1288-1300. doi: 10.1080/09205063.2021.1912976. Epub 2021 May 18.

Abstract

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.

摘要

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)。

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