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植入型环糊精聚合物递送白藜芦醇对植入式神经探针提供持续的抗氧化作用。

Resveratrol Delivery from Implanted Cyclodextrin Polymers Provides Sustained Antioxidant Effect on Implanted Neural Probes.

机构信息

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.

Affinity Therapeutics, LLC, 11000 Cedar Avenue, Suite 285, Cleveland, OH 44106, USA.

出版信息

Int J Mol Sci. 2020 May 19;21(10):3579. doi: 10.3390/ijms21103579.

Abstract

Intracortical microelectrodes are valuable tools used to study and treat neurological diseases. Due in large part to the oxidative stress and inflammatory response occurring after electrode implantation, the signal quality of these electrodes decreases over time. To alleviate this response, resveratrol, a natural antioxidant which elicits neuroprotective effects through reduction of oxidative stress, was utilized. This work compares traditional systemic delivery of resveratrol to the novel cyclodextrin polymer (pCD) local delivery approach presented herein, both in vitro and in vivo. The pCD displayed an extended resveratrol release for 100 days, as well as 60 days of free radical scavenging activity in vitro. In vivo results indicated that our pCD delivery system successfully delivered resveratrol to the brain with a sustained release for the entire short-duration study (up to 7 days). Interestingly, significantly greater concentrations of resveratrol metabolites were found at the intracortical probe implantation site compared to the systemic administration of resveratrol. Together, our pilot results provide support for the possibility of improving the delivery of resveratrol in an attempt to stabilize long-term neural interfacing applications.

摘要

皮层内微电极是用于研究和治疗神经疾病的有价值的工具。由于电极植入后发生的氧化应激和炎症反应,这些电极的信号质量会随时间降低。为了减轻这种反应,利用了白藜芦醇,一种天然抗氧化剂,通过减少氧化应激来发挥神经保护作用。这项工作比较了传统的全身给予白藜芦醇与本文提出的新型环糊精聚合物(pCD)局部给予方法,包括在体和在体。pCD 显示出长达 100 天的白藜芦醇延长释放,以及体外 60 天的自由基清除活性。体内结果表明,我们的 pCD 递送系统成功地将白藜芦醇递送到大脑中,并在整个短期研究(长达 7 天)内持续释放。有趣的是,与全身给予白藜芦醇相比,在皮层内探针植入部位发现了浓度显著更高的白藜芦醇代谢物。总之,我们的初步结果为改善白藜芦醇的递送以试图稳定长期神经接口应用提供了支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc95/7279014/9ed4eed7cb3c/ijms-21-03579-g001.jpg

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