I-Corps: Magnetic nanoparticles as a magnetic resonance imaging and angiography contrast agent

I-Corps：磁性纳米粒子作为磁共振成像和血管造影造影剂

• 批准号: 1818465
• 负责人: Allan David
• 金额: $ 5万
• 依托单位: Auburn University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1818465&HistoricalAwards=false
• 关键词: Corps; Magnetic; nanoparticles; magnetic; resonance

The broader impact/commercial potential of this I-Corps project is the development of improved magnetic nanoparticles with safer profiles for biomedical applications. One specific market would be contrast agents for magnetic resonance imaging (MRI). Current gadolinium-based contrast agents (GBCAs) cannot be administered to patients with poor renal function, and more recent clinical studies indicated long-term residual gadolinium deposition in the brains of healthy patients. As gadolinium is the source of safety concerns for current GBCAs, one possible solution is to replace gadolinium with bio-compatible iron-oxides that offer similar contrast enhancement. Conventional iron-based MRI contrast agents have a broad particle size distribution which results in undesired side effects and performance variability. The technology developed here enables tight control of particle size distribution and physicochemical properties, which improves the agent's performance and safety profile. Moreover, an iron-based contrast agent can be used as a contrast agent for magnetic resonance angiography (MRA) of peripheral vascular diseases.This I-Corps project further develops a technology that enables the explicit control of the physicochemical properties of iron-oxide nanoparticles. These nanoparticles offer potential as magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) contrast agents that overcome the safety limitations of currently used alternatives. Iron-oxide nanoparticles have been previously approved for clinical use as MRI contrast agents but were discontinued from the market due to variable performance and safety concerns - primarily due to formulations with a broad size distribution. The technology developed here enables the production of iron-oxide nanoparticles with highly controlled physiochemical properties and low batch-to-batch variability which yield reproducible MRI results. This homogenous formulation is expected to have more controlled pharmacokinetics and biodistribution profiles compared to conventional iron-based agents.

这个I-Corps项目的更广泛的影响/商业潜力是开发具有更安全的生物医学应用的磁性纳米颗粒。一个具体的市场是磁共振成像（MRI）的造影剂。目前的钆基造影剂（GBCA）不能用于肾功能差的患者，最近的临床研究表明，健康患者的大脑中存在长期残留钆沉积。由于钆是当前GBCA安全问题的根源，一种可能的解决方案是用具有类似对比度增强作用的生物相容性铁氧化物取代钆。常规的铁基MRI造影剂具有宽的粒度分布，这导致不期望的副作用和性能可变性。这里开发的技术可以严格控制粒度分布和物理化学性质，从而提高药剂的性能和安全性。此外，铁基造影剂还可以作为周围血管疾病的磁共振血管造影（MRA）的造影剂。I-Corps项目进一步开发了能够明确控制氧化铁纳米粒子的物理化学性质的技术。这些纳米颗粒提供了磁共振成像（MRI）和磁共振血管造影（MRA）造影剂的潜力，克服了目前使用的替代品的安全性限制。氧化铁纳米颗粒之前已被批准用于临床MRI造影剂，但由于性能和安全性问题而停止上市-主要是由于具有广泛尺寸分布的制剂。这里开发的技术能够生产具有高度受控的理化性质和低批次间变异性的氧化铁纳米颗粒，从而产生可重现的MRI结果。与传统的铁基制剂相比，这种均匀的制剂预计具有更可控的药代动力学和生物分布特征。