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微针贴片在递送蜂毒方面提供的药代动力学改善,以对抗小鼠模型中东莨菪碱诱导的神经退行性变的案例研究。

Pharmacokinetic improvement provided by microneedle patch in delivering bee venom, a case study in combating scopolamine-induced neurodegeneration in mouse model.

机构信息

College of Korean Medicine, Dongshin University, Naju, Korea.

Department of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Dongshin University, Naju,Gwangju, Korea.

出版信息

Drug Deliv. 2022 Dec;29(1):2855-2867. doi: 10.1080/10717544.2022.2116129.

Abstract

Much research has shown Bee venom to be an effective neuroprotective agent. However, the usual transdermal injection of bee venom poses many pharmacokinetic disadvantages. Here, we compared the administration of bee venom via subcutaneous injection (SC) and via Microneedle patch (MN). Both administrated routes produce significant recovery effects, however: the MN significantly prolongs the bio-significant-and-yet-lower concentration of bee venom in mice bodies. In contrast, SC could produce only a short period of much higher bee venom levels in the blood and brain. We also see that due to the concentration-response-curve of bee venom (represented by melittin): mice bodies do not require much higher bee venom concentration (seen in the SC group) to produce a much more significant neuroprotective effect (than seen in those treated with the MN method). Therefore, a MN could maintain bee venom levels in mice bodies at lower-yet-more-efficient concentrations. This is important, as bee venom can cause more adverse effects and pain sensations, at higher concentrations. For the first time, we confirmed that the pharmacokinetic advantages of MN delivered bee venom also guarantee a holistic neuroprotection effect (which was shown by SC delivered bee venom in previous research). This was proven via the results of the water maze experiments for long-term learning memory assessment and protein analysis of key neuronal regulatory proteins: BDNF, p-CREB, iNOS, and mArhR 1. In conclusion, for situations where we ought to administrate drugs at a more downward amount, such as bee venom, MN can keep the therapeutic concentrations at a lower, yet interestingly, more-efficient level.

摘要

大量研究表明蜂毒是一种有效的神经保护剂。然而,通常的透皮注射蜂毒存在许多药代动力学上的缺点。在这里,我们比较了皮下注射(SC)和微针贴片(MN)给药途径。这两种给药途径都产生了显著的恢复效果,然而:MN 显著延长了蜂毒在小鼠体内的生物显著且浓度更低的时间。相比之下,SC 只能在血液和大脑中产生短暂的高得多的蜂毒水平。我们还发现,由于蜂毒的浓度-反应曲线(由蜂毒素表示):小鼠体内不需要更高的蜂毒浓度(在 SC 组中看到)来产生更显著的神经保护作用(比用 MN 方法治疗的效果更显著)。因此,MN 可以使蜂毒在小鼠体内保持在更低但更有效的浓度。这很重要,因为在更高的浓度下,蜂毒会引起更多的不良反应和疼痛感觉。这是第一次证实 MN 输送的蜂毒的药代动力学优势也保证了整体的神经保护作用(这是以前的研究中 SC 输送的蜂毒所证明的)。这是通过水迷宫实验的结果来证明的,用于长期学习记忆评估和关键神经元调节蛋白的蛋白质分析:BDNF、p-CREB、iNOS 和 mArhR1。总之,在需要以更低的剂量给药的情况下,例如蜂毒,MN 可以将治疗浓度保持在较低但有趣的是更有效的水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e118/9448392/1b488eebdf22/IDRD_A_2116129_F0001_C.jpg

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