Application and Safety of Externally Controlled Metronomic Drug Delivery to the Brain by an Implantable Smart Pump in a Sheep Model.

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Neurosurgery Pub Date : 2024-09-06 DOI:10.1227/neu.0000000000003155

Thomas C Chen, Winston H Wu, Ki-Eun Chang, Axel H Schönthal, Eli S Gang, Vic Indravudh, Thomas Lobl, Frank Adell, Yehoshua Shachar

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Abstract

Background and objectives: Intraventricular drug delivery enables the delivery of therapeutics to the central nervous system, while minimizing peripheral drug exposure and toxicity. However, currently used delivery devices cannot be controlled externally to adjust their output during delivery. Here, the authors investigated the performance of a conceptually novel device designed to metronomically deliver a drug to the cerebrospinal fluid in a manner that can be adjusted wirelessly from an external controller.

Methods: Six sheep were subcutaneously implanted in the shoulder region with a drug delivery pump and a catheter connecting to the brain ventricles. Three groups of 2 sheep received low, medium, and high dosages of metronomic methotrexate (MTX) over several weeks, while kept mobile outdoors in a pen. MTX dosages were adjusted from a wireless external controller, and intraventricular MTX concentrations were measured in regular intervals with an Ommaya reservoir.

Results: Over the course of this 12-week study, sheep showed no signs of toxicity. MTX measurements in the cerebrospinal fluid confirmed that the pump remained responsive to external control and able to deliver drug in an adjustable, metronomic fashion.

Conclusion: This implantable pump system enables external control of drug output, so that the resulting intraventricular drug concentrations can continuously be maintained within the therapeutic range.

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在绵羊模型中通过植入式智能泵向大脑输送外部控制的元组学药物的应用和安全性。

背景和目标：静脉内给药可将治疗药物输送到中枢神经系统，同时最大限度地减少外周药物暴露和毒性。然而，目前使用的给药装置无法通过外部控制来调整给药过程中的输出量。在此，作者研究了一种概念新颖的装置的性能，该装置可通过外部控制器进行无线调节，以节律方式向脑脊液输送药物：方法：在六只绵羊的肩部皮下植入一个给药泵和一根连接脑室的导管。三组各 2 只绵羊分别在数周内接受低、中、高剂量的甲氨蝶呤（MTX）治疗，并在户外圈养。MTX的剂量由无线外部控制器进行调整，并定期用Ommaya储液器测量脑室内MTX的浓度：结果：在为期 12 周的研究过程中，绵羊没有出现中毒症状。脑脊液中的 MTX 测量结果证实，该泵对外部控制仍有反应，并能以可调节的节律方式输送药物：结论：这种植入式泵系统能够从外部控制药物输出，从而使静脉内药物浓度持续保持在治疗范围内。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurosurgery 医学-临床神经学

CiteScore

8.20

自引率

6.20%

发文量

898

审稿时长

2-4 weeks

期刊介绍： Neurosurgery, the official journal of the Congress of Neurological Surgeons, publishes research on clinical and experimental neurosurgery covering the very latest developments in science, technology, and medicine. For professionals aware of the rapid pace of developments in the field, this journal is nothing short of indispensable as the most complete window on the contemporary field of neurosurgery. Neurosurgery is the fastest-growing journal in the field, with a worldwide reputation for reliable coverage delivered with a fresh and dynamic outlook.

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