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

使用新型适体生物传感器对大脑进行高精度药代动力学测量

• 批准号: 10000950
• 负责人: Philip Andrew Vieira
• 金额: $ 14.23万
• 依托单位: CALIFORNIA STATE UNIV-DOMINGUEZ HILLS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-22 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10000950
• 关键词: Animal Model; Biosensing Techniques; Biosensor; Blood - brain barrier anatomy; Brain; California; Cocaine; Collaborations; Communities; Data; Detection; Development; Dose; Doxorubicin; Drug Kinetics; Drug Monitoring; Drug Targeting; Drug abuse; Drug usage; Epidemic; Excision; Excretory function; Foundations; Future; Goals; Grant; Health; Hour; Human; Illicit Drugs; In Vitro; Laboratories; Location; Measurement; Measures; Mentors; Metabolism; Methodology; Methods; Microdialysis; Minority-Serving Institution; Modification; Monitor; Neuraxis; Overdose; Oxycodone; Pharmaceutical Preparations; Positioning Attribute; Procedures; Protocols documentation; Rattus; Research; Research Personnel; Resolution; Risk; Sampling; Social Class; Substance Addiction; Substance abuse problem; Techniques; Technology; Testing; Therapeutic; Time; Toxic effect; Training; Treatment Efficacy; Universities; Work; addiction; aptamer; awake; base; blood-brain barrier crossing; clinically relevant; drug action; drug efficacy; drug metabolism; drug of abuse; experimental study; improved; in vivo; new technology; new therapeutic target; novel; novel therapeutics; opioid epidemic; prescription opioid; prevent; professor; programs; real time monitoring; response; sensor; side effect; temporal measurement; tool; ultra high resolution; uptake

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.

项目摘要/摘要 摘要：一种新型适体在脑内的高精度药代动力学测量 生物传感器 描述一种药物的成瘾潜能与其相互作用的速度有关 大脑。药物滥用对于处方药来说尤其成问题，因为它们是一种 是目前成瘾流行的主要原因。为了提高药物的疗效和 为了减轻毒性，监测药物的药代动力学至关重要。传统的方法 监测药物药代动力学需要通过以下方法从大脑中移除样本 用于以后实验室分析的微透析，使它们变得缓慢和繁琐 极大地限制了它们的时间分辨率。相比之下，一种新型电化学材料的开发 导师团队推出的基于适体(E-AB)的生物传感器为连续、 对活体受试者的药物进行超高分辨率监测。例如，PI已经使用 这项技术能够测量多个药物靶点，显示出准确、高精度 这些化合物在体内多小时内的药代动力学(秒分辨)跟踪 动物模型。为了扩展这一了解药物新陈代谢的有希望的平台，PI将 应用它来表征跨越血脑屏障的化合物的药代动力学 (Bbb)。这些药物将包括处方类阿片羟考酮和令人上瘾的非法药物。 可卡因。在这里，PI打算实现E-AB传感器来实时测量 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 药物跨越血脑屏障的时间进程，但也展示了这一功能 潜在的革命性新药代动力学工具。为此，国际和平研究所提出了以下建议 具体目标：1)将E-AB传感器的高精度体外应用扩展到新的药物靶点； 2)将E-AB传感器扩展到大脑测量。成功完成这些任务 AIMS不仅将在PI的实验室中建立这种新的技术和方法，而且还将 也进一步开发技术，以测量新的，临床相关的化合物在新的和 重要的地理位置。此外，这项工作将有助于将PI作为一项独立的研究 研究人员未来寻求非得分支持，以扩大他的研究计划。