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基于金纳米棒的温敏水凝胶通过瞬时受体电位香草素 1 型通道的光热激活产生选择性的长效局部麻醉。

Gold nanorods-based thermosensitive hydrogel produces selective long-lasting regional anesthesia triggered by photothermal activation of Transient Receptor Potential Vanilloid Type-1 channels.

机构信息

Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, and Department of Anesthesiology, West China Hospital of Sichuan University, Sichuan, Chengdu, 610041, PR China.

Department of Burn and Plastic Surgery, West China Hospital of Sichuan University, Sichuan, Chengdu, 610041, PR China.

出版信息

Colloids Surf B Biointerfaces. 2018 Nov 1;171:17-23. doi: 10.1016/j.colsurfb.2018.07.002. Epub 2018 Jul 6.

DOI:10.1016/j.colsurfb.2018.07.002
PMID:30005286
Abstract

Long-lasting regional anesthesia and selective sensory block are useful in post-operative analgesia and treatment of pathological pain. Previous studies have demonstrated that activation of TRPV1 (Transient Receptor Potential Vanilloid Type-1) channels facilitated the potency of QX-314 for selective long-lasting regional anesthesia in vivo. Hydrogel is a solid jelly-like material covering a wide range of properties from soft and weak to hard and tough. Gold nanorods are nanoparticles, which can be used for hyperthermia by exposure to near-infrared radiation. We fabricated a gold nanorods and QX-314 containing hydrogel. The molecular weight of hydrogel was adjusted to achieve a targeted phase transition temperature. Gold nanorods with a desired photothermal conversion efficacy and QX-314 were mixed with hydrogel to produce a gold nanorods-QX-314/hydrogel nanocomposite. A rat model of sciatic nerve block was applied to evaluate the regional anesthetic effect of the gold nanorods-QX-314/hydrogel nanocomposite. Upon exposure to near-infrared irradiation, the gold nanorods-QX-314/hydrogel nanocomposite activated TRPV1 channels through photothermal conversion and release of QX-314 at the same time. The gold nanorods and QX-314 loaded hydrogel exhibited a long-lasting regional anesthetic effect with selective sensory function block. Sensory block duration of the nanocomposite was significantly longer than of 1% lidocaine (90.0 ± 12.2 vs. 37.5 ± 12.5 min, P < 0.01). Motor block by the nanocomposite was observed for only 40% of rats with significantly shorter duration than its sensory block (42.5 ± 17.1 vs. 90.0 ± 12.2 min, P < 0.01). The gold nanorods-QX-314/hydrogel nanocomposite can produce a selective long-lasing regional anesthetic effect in a rat model of sciatic nerve block.

摘要

长效局部麻醉和选择性感觉阻滞在术后镇痛和病理性疼痛治疗中很有用。先前的研究表明,TRPV1(瞬时受体电位香草素 1 型)通道的激活促进了 QX-314 在体内选择性长效局部麻醉的效力。水凝胶是一种固态果冻状物质,具有从柔软和弱到坚硬和坚韧等广泛的性质。金纳米棒是纳米颗粒,可以通过暴露于近红外辐射来进行热疗。我们制备了一种含有金纳米棒和 QX-314 的水凝胶。水凝胶的分子量进行了调整,以达到目标相转变温度。将具有所需光热转换效率的金纳米棒和 QX-314 与水凝胶混合,制备出金纳米棒-QX-314/水凝胶纳米复合材料。应用大鼠坐骨神经阻滞模型来评估金纳米棒-QX-314/水凝胶纳米复合材料的局部麻醉效果。在近红外辐射下,金纳米棒-QX-314/水凝胶纳米复合材料通过光热转换同时激活 TRPV1 通道并释放 QX-314。负载金纳米棒和 QX-314 的水凝胶表现出具有选择性感觉功能阻滞的长效局部麻醉作用。纳米复合材料的感觉阻滞持续时间明显长于 1%利多卡因(90.0±12.2 与 37.5±12.5 分钟,P<0.01)。纳米复合材料观察到的运动阻滞仅发生在 40%的大鼠中,其持续时间明显短于感觉阻滞(42.5±17.1 与 90.0±12.2 分钟,P<0.01)。金纳米棒-QX-314/水凝胶纳米复合材料可在大鼠坐骨神经阻滞模型中产生选择性长效局部麻醉作用。

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