In-Vivo Monitoring of Therapeutic Drug Transport Across Biological Barriers
治疗药物跨生物屏障转运的体内监测
基本信息
- 批准号:10094296
- 负责人:
- 金额:$ 36.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:AcidityAffectAminoglycosidesAmoxicillinAmpicillinAntibiotic ProphylaxisAntibioticsBacteriaBehaviorBiologicalBiopsyBloodBlood capillariesBrainBrain InjuriesBrain regionCell LineCerebrospinal FluidCharacteristicsChemical StructureChemicalsChemoreceptorsClinicalComplexDangerousnessDataDetectionDevelopmentDoseDrug KineticsDrug TransportEndotheliumEnvironmentExposure toExtracellular SpaceFamilyFoundationsFutureGentamicinsGlycopeptide AntibioticsGlycopeptidesGoalsHippocampus (Brain)ImplantIn VitroIndustryInfectionKanamycinKineticsKnowledgeLibrariesLiverMapsMeasurementMeasuresMediatingMedicalMembraneMethodologyModelingMolecularMonitorMonobactamsNatureOperative Surgical ProceduresOrganPenetrating Brain InjuryPenetrationPenicillin GPerfusionPermeabilityPharmaceutical PreparationsPharmacotherapyPreparationProphylactic treatmentProstateProstaticRattusRegimenResearchResearch PersonnelResistance developmentResourcesSamplingStructureStructure of jugular veinTestingThalamic structureTherapeuticTherapeutic AgentsTimeTissuesTobramycinTransport ProcessTravelVancomycinWorkaptamerbasebeta-Lactamsblood cerebrospinal fluid barrierchemical propertycostdrug developmentimprovedin vivoin vivo evaluationin vivo monitoringnovel therapeuticspassive transportprecision drugspredictive modelingpreventprogramsreal time monitoringresponsesensorsensor technologyside effectstandard of caretemporal measurementtherapeutically effectivetumoruptakewearable sensor technologywound
项目摘要
Project Summary
The ability of therapeutic drugs to access specific organs strongly depends on the nature of the blood-tissue
barrier at said organs. The prostate and brain, for example, have tight barriers with no intercellular gaps, and
most drugs cannot permeate them at sufficiently high levels to be therapeutically effective. Thus, understanding
the relationships between drug chemical structure, dosing regimen, and organ penetration is crucial to
the development of new and effective drug therapies. Motivated by this, the long-term goal of this program
is to establish a measurement standard of molecular transport parameters affecting the passage of therapeutic
agents across biological barriers in vivo. Specifically, the objective of this proposal is to demonstrate that
electrochemical, aptamer-based (E-AB) sensors – an emerging sensing platform with the ability to continuously
measure the levels of specific molecules in the body – can support continuous monitoring of molecular transport
from blood to liver, prostate and brain. The proposed measurements will determine the transport parameters of
seven therapeutic agents (three aminoglycoside, three β-lactam and one glycopeptide antibiotics) across four
biological barriers (i.e., blood-liver, blood-prostate, blood-brain and blood-cerebrospinal fluid). These drugs were
chosen because, although effective at treating infections across organ barriers, they cause dangerous side
effects driven by their narrow therapeutic window, making their precise dosing an important medical challenge.
The central hypothesis of this work is that achieving spatially and temporally resolved drug measurements in
blood and target organs will produce unprecedented permeability data that will guide new therapeutic drug
development toward the creation of permeability-enhanced therapeutics and more effective dosing regimens.
This hypothesis will be tested by pursuing three specific aims: 1) Determine the kinetics of drug uptake in the
liver via continuous, seconds-resolved E-AB measurements; 2) Determine the transport kinetics of antibiotics
through the prostatic barrier; and 3) Determine the transport kinetics of prophylaxis antibiotics delivered from
blood to the brain. The proposed research is significant because it will define the structural and transport
characteristics necessary for therapeutic agents to penetrate targeted organs and propel the study of other
therapeutics beyond the families of antibiotics considered here. Thus, this work will develop foundational
knowledge and generate the necessary resources for other researchers and industries – working on drug
development, in-vivo testing and clinical dose scaling – to advance the field of therapeutics. The proposed
research will have an immediate positive impact as it will establish a better understanding of therapeutic drug
transport within compartments in the body. Longer term, this work will have established the groundwork
necessary for the in-vivo evaluation of molecular transport across tight biological barriers.
项目摘要
治疗药物进入特定器官的能力在很大程度上取决于血液组织的性质
这些器官的屏障。例如,前列腺和大脑有紧密的屏障,没有细胞间的间隙,
大多数药物不能以治疗有效的足够高的水平渗透它们。因此,理解
药物化学结构、给药方案和器官渗透之间的关系对于
开发新的有效的药物疗法。受此启发,该计划的长期目标
建立影响药物通过的分子转运参数的测量标准
药物在体内穿过生物屏障。具体而言,本提案的目的是表明,
电化学,基于适体(E-AB)的传感器-一种新兴的传感平台,能够连续
测量体内特定分子的水平-可以支持对分子运输的持续监测
从血液到肝脏前列腺和大脑建议的测量将确定的运输参数
七种治疗药物(三种氨基糖苷类、三种β-内酰胺类和一种糖肽类抗生素),
生物屏障(即,血-肝、血-前列腺、血-脑和血-脑脊液)。这些药物
之所以选择它,是因为尽管它能有效治疗跨越器官屏障的感染,
由于其狭窄的治疗窗口,使其精确给药成为一项重要的医学挑战。
这项工作的中心假设是,实现空间和时间分辨的药物测量,
血液和靶器官将产生前所未有的渗透性数据,
因此,本领域的技术人员将致力于开发渗透性增强的治疗剂和更有效的给药方案。
将通过追求三个具体目标来测试该假设:1)确定在小鼠中药物摄取的动力学。
通过连续的、秒分辨的E-AB测量肝脏; 2)确定抗生素的转运动力学
通过前列腺屏障;和3)确定从前列腺屏障递送的预防性抗生素的转运动力学。
血液进入大脑。拟议的研究是重要的,因为它将定义结构和运输
治疗剂渗透靶器官并推动其他靶器官的研究所必需的特征
抗生素家族之外的治疗方法。因此,这项工作将发展基础
知识和产生必要的资源,为其他研究人员和行业-工作的药物
开发、体内测试和临床剂量缩放-推进治疗领域。拟议
研究将产生直接的积极影响,因为它将建立对治疗药物的更好理解,
在体内的隔室中运输。从长远来看,这项工作将奠定基础
这是体内评价分子穿过紧密生物屏障转运所必需的。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Netzahualcoyotl Arroyo Curras其他文献
Netzahualcoyotl Arroyo Curras的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Netzahualcoyotl Arroyo Curras', 18)}}的其他基金
In-Vivo Monitoring of Therapeutic Drug Transport Across Biological Barriers
治疗药物跨生物屏障转运的体内监测
- 批准号:
10677650 - 财政年份:2021
- 资助金额:
$ 36.75万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 36.75万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 36.75万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 36.75万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 36.75万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 36.75万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 36.75万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 36.75万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 36.75万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 36.75万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 36.75万 - 项目类别:
Studentship