High precision pharmacokinetic measurements in brain using a novel aptamer-based biosensor

项目总结/摘要 翻译后摘要：使用一种新的基于适体的高精度脑药代动力学测量 生物传感 药物的成瘾潜力与其与药物相互作用的速率有关。 大脑药物滥用对于处方治疗药物来说尤其成问题，因为它们是一种 是造成当前成瘾流行的主要原因为了提高药效， 为了减轻毒性，监测药物的药代动力学至关重要。的传统方法 监测药物的药代动力学需要从大脑中取出样品， 微透析用于实验室中的后续分析，使其缓慢而繁琐， 极大地限制了它们的时间分辨率。相比之下，开发一种新型的电化学 基于适体（E-AB）的生物传感器由导师的小组打开了大门， 超高分辨率监测活体药物。例如，PI已经使用 这项技术可以测量多个药物靶点， 这些化合物在活体中多小时内的（秒分辨）药代动力学跟踪 动物模型为了扩大这个有前途的平台，了解药物代谢，PI将 将其应用于表征穿过血脑屏障的化合物的药代动力学 （BBB）。其中包括处方阿片类药物羟考酮和成瘾性非法药物 可卡因在这里，PI打算实施E-AB传感器来测量实时 这些化合物在大脑中的药代动力学，从而不仅提高了我们对 药物穿过BBB的时间过程，但也要证明这一功能 可能是革命性的新药代动力学工具。为此，PI提出以下建议： 具体目标：1）将E-AB传感器的高精度体外使用扩展到新的药物靶点; 2)扩展E-AB传感器以测量大脑。成功完成这些 目标不仅将在PI的实验室中建立这种新的技术和方法， 还进一步开发技术，以测量新的，临床相关的化合物， 重要的位置。此外，这项工作将有助于发展PI作为一个独立的研究 研究人员寻求非SCORE的支持，在未来扩大他的研究计划。

Project Summary/Abstract Abstract: High precision pharmacokinetic measurements in brain using a novel aptamer-based biosensor DESCRIPTION The addiction potential of a drug is related to the rate at which it interacts with the brain. Drug abuse is particularly problematic for prescribed therapeutic drugs as they are a major contributor to the current addiction epidemic. In order to increase drug efficacy and mitigate toxicity, it is crucial to monitor drug pharmacokinetics. Traditional methods for monitoring drug pharmacokinetics require the removal of samples from the brain by microdialysis for later analysis in the laboratory, rendering them slow and cumbersome and greatly limiting their temporal resolution. In contrast, the development of a novel electrochemical aptamer-based (E-AB) biosensor by the mentor's group has opened the door for the continuous, ultra-high-resolution monitoring of drugs in living subjects. For example, the PI has already used this technology to measure multiple drug targets, demonstrating accurate, high-precision (seconds-resolved) pharmacokinetic tracking of these compounds over multiple hours in a live animal model. To expand this promising platform for understanding drug metabolism, the PI will apply it to characterizing the pharmacokinetics of compounds that cross the blood-brain barrier (BBB). These will include the prescription opioid oxycodone and the addictive illicit drug cocaine. Here, the PI intends to implement E-AB sensors to measure the real-time pharmacokinetics these compounds in brain, thus not only improving our understanding of the time course of drugs crossing the BBB, but to also demonstrate the functionality of this potentially revolutionary new pharmacokinetic tool. To that end, the PI proposes the following specific aims: 1) Expansion of high precision in vitro use of E-AB sensors to novel drug targets; 2) Expansion of E-AB sensors to measurements in the brain. Successful completion of these aims will not only establish this novel technology and methodology in the PI's laboratory, but will also further develop the technology to measure new, clinically-relevant compounds in a new and important location. Additionally, this work will help develop the PI as an independent research investigator to seek non-SCORE support in the future to expand his research program.