Bio-electrochemical detectors for in vivo continuous monitoring

用于体内连续监测的生物电化学检测器

• 批准号: 10394638
• 负责人: Tod Edward Kippin
• 金额: $ 63.74万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10394638
• 关键词: Animal Model; Antibiotics; Area Under Curve; Biological Markers; Biomedical Research; Blood; Blood Glucose; Brain; Cerebrospinal Fluid; Chemicals; Clinical; Clinical Pharmacology; Complex; Dangerousness; Diabetes Mellitus; Dose; Dose-Limiting; Drug Delivery Systems; Drug Exposure; Drug Kinetics; Drug Monitoring; Drug Transport; Elements; Ensure; Feedback; Female; Funding; Goals; Grant; Health; Immunosuppressive Agents; In Situ; Intestines; Intravenous; Knowledge; Lead; Liquid substance; Measurement; Measures; Metabolic; Molecular; Monitor; Outcome; Patients; Pharmaceutical Preparations; Pharmacology Study; Plasma; Precision therapeutics; Property; Rattus; Regimen; Reporting; Research; Resolution; Safety; Sensitivity and Specificity; Sex Differences; Solid; Surveys; Technology; Therapeutic; Therapeutic Index; Time; Tissues; Toxic effect; Variant; Venous; Women' s Health; antimicrobial; aptamer; base; clinical decision-making; clinical practice; clinically relevant; cost effective; detector; drug disposition; drug efficacy; drug metabolism; glucose monitor; improved; in vivo; in vivo monitoring; infectious disease treatment; innovation; insight; minimally invasive; sensor; standard of care; stem; subcutaneous; temporal measurement; tool; wearable device

Summary. Our overarching goal is to render therapeutic drug monitoring as convenient and highly time resolved as the continuous glucose monitor has rendered the monitoring of blood sugar. The realization of this goal would transform many aspects of both biomedical research and clinical practice. It would, for example, enable personalized dosing based on a patient’s accurately determined, rather than poorly predicted, drug metabolism, an outcome of high relevance to the treatment of infectious diseases, which commonly employs drugs of dangerously narrow therapeutic index, and to improving women’s health, as pharmacokinetic sex differences lead to a doubling of adverse pharmacotherapeutic outcomes in females. Ultimately such a technology could enable feedback-controlled drug dosing, which, by responding in real time to metabolic variations, would improve the safety and efficacy of drugs that suffer from dose-limiting toxicity. To achieve our goal, however, requires two significant innovations: (1) a technology able to monitor arbitrary drug molecules in situ in the intestinal fluid (ISF) of the subcutaneous space and (2) vastly improved knowledge regarding how the pharmacokinetics of drugs in the ISF relate to the pharmacokinetics seen in plasma. Under the prior round of grant funding, we achieved the first of these necessary advances. Specifically, we demonstrated that minimally-invasive Electrochemical, Aptamer-Based (EAB) sensors support the seconds-resolved, real-time measurement of drugs in situ in the plasma (venous), cerebrospinal fluid (brain), and ISF (subcutaneous space) of our live rat animal model. Here we propose to tackle the second innovation. That is, using intravenous and subcutaneous EAB sensors we propose to advance understanding of the relationships between plasma and ISF pharmacokinetics across a diverse set of antimicrobial and immunosuppressant drugs for which therapeutic drug monitoring is an important element of the standard of care. We believe the resulting orders of magnitude improvement in measuring these relationships is a critical step towards our long-range goal of rendering high-precision therapeutic drug monitoring convenient and cost effective.

总结 我们的首要目标是使治疗药物监测变得方便且具有高度的时间分辨率。 随着连续血糖监测仪的出现，血糖的监测就实现了这一目标。 例如，它将改变生物医学研究和临床实践的许多方面。 根据患者准确确定的药物代谢而不是错误预测的药物代谢进行个性化剂量， 与感染性疾病的治疗高度相关的结果，通常使用以下药物 危险地缩小治疗指数，并改善女性健康，因为药代动力学性别差异 最终，这种技术可能会导致女性的不良药物治疗结果加倍。 实现反馈控制的药物剂量，通过实时响应代谢变化，可以改善 然而，为了实现我们的目标，需要确保具有剂量限制性毒性的药物的安全性和有效性。 两项重大创新：(1) 能够原位监测肠液中任意药物分子的技术 （ISF）的皮下空间和（2）极大地提高了关于如何药代动力学的知识 ISF 中的药物与血浆中的药代动力学相关。 具体来说，我们证明了微创 基于适配体 (EAB) 的电化学传感器支持药物的秒级分辨实时测量 活体大鼠血浆（静脉）、脑脊液（大脑）和 ISF（皮下空间）中的原位 这里我们建议解决第二个创新，即使用静脉内和皮下EAB。 我们建议使用传感器来加深对血浆和 ISF 药代动力学之间关系的理解 涵盖多种抗菌药物和免疫抑制剂药物，其中治疗药物监测是 我们相信由此带来的护理标准的数量级改善。 测量这些关系是实现我们渲染高精度的长期目标的关键一步 治疗药物监测方便且具有成本效益。