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近红外光激活水凝胶用于递送二甲双胍。

Near-infrared light activatable hydrogels for metformin delivery.

机构信息

Univ. Lille, CNRS, Centrale Lille, ISEN, Univ. Valenciennes, UMR 8520 - IEMN, F-59000 Lille, France.

出版信息

Nanoscale. 2019 Aug 29;11(34):15810-15820. doi: 10.1039/c9nr02707f.

Abstract

Drug loaded hydrogels have proven to be versatile controlled-release systems. We report here on heat active hydrogel formation by mixing graphene oxide (GO) or carboxyl enriched reduced graphene oxide (rGO-COOH) with metformin hydrochloride, an insulin sensitizer drug currently used as the first line therapy to treat patients with type 2 diabetes. The driving forces of the gelation process between the graphene-based nanomaterial and metformin are hydrogen bonding and electrostatic interactions, weakened at elevated temperature. Using the excellent photothermal properties of the graphene matrixes, we demonstrate that these supramolecular drug reservoirs can be photothermally activated for transdermal metformin delivery. A sustained delivery of metformin was achieved using a laser power of 1 W cm-2. In vitro assessment of the key target Glucose-6 Phosphatase (G6P) gene expression using a human hepatocyte model confirmed that metformin activity was unaffected by photothermal activation. In vivo, metformin was detected in mice plasma at 1 h post-activation of the metformin loaded rGO-COOH gel.

摘要

载药水凝胶已被证明是一种多功能的控释系统。我们在此报告了通过将氧化石墨烯(GO)或富含羧基的还原氧化石墨烯(rGO-COOH)与盐酸二甲双胍混合来形成热响应水凝胶的情况,盐酸二甲双胍是一种目前用于治疗 2 型糖尿病患者的一线治疗药物。基于石墨烯的纳米材料与盐酸二甲双胍之间的凝胶化过程的驱动力是氢键和静电相互作用,在高温下会减弱。利用石墨烯基质的优异光热性能,我们证明这些超分子药物储库可以通过光热作用来激活经皮递送盐酸二甲双胍。使用 1 W cm-2 的激光功率实现了盐酸二甲双胍的持续递送。使用人肝细胞模型对关键靶标葡萄糖-6-磷酸酶(G6P)基因表达的体外评估证实,光热激活对盐酸二甲双胍的活性没有影响。在体内,在激活负载 rGO-COOH 的盐酸二甲双胍凝胶后 1 小时,在小鼠血浆中检测到盐酸二甲双胍。

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