Nanoparticle- Infused Radiopaque Absorbable Medical Device

纳米颗粒注入不透射线可吸收医疗器械

• 批准号: 10442452
• 负责人: Marites Pasuelo Melancon
• 金额: $ 38.63万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10442452
• 关键词: Adverse effects; Adverse event; Adverse reactions; Affect; Algorithms; American; Animals; Anticoagulants; Anticoagulation; Autopsy; Barium; Bismuth; Blood Circulation Time; Blood Vessels; Blood coagulation; Calcium; Cardiovascular Diseases; Cardiovascular system; Catheters; Chronic; Clinical; Coagulation Process; Complex; Contrast Media; Deep Vein Thrombosis; Deposition; Development; Devices; Disadvantaged; Discrimination; Disease; Dose; Electrospinning; Elements; Embolism; Enhancers; Event; Excision; Exhibits; Failure; Fatigue; Filtration; Fluoroscopy; Fracture; Goals; Gold; Hemorrhage; Hospitalization; Human; Hydrolysis; Hypersensitivity; Image; Image Enhancement; Imaging Techniques; In Vitro; Infusion procedures; Intervention; Iodine; Lead; Life; Lung; Mechanics; Medical Device; Metals; Methods; Monitor; Nail plate; Operative Surgical Procedures; Organ; Orthopedics; Patients; Pharmacologic Substance; Physiological; Plague; Polymers; Population; Positioning Attribute; Prevention; Procedures; Property; Public Health; Pulmonary Embolism; Reporting; Research; Retrieval; Risk; Rod; Roentgen Rays; Signal Transduction; Stroke; Surgical sutures; System; Tantalum; Testing; Therapeutic Embolization; Thrombus; Time; Toxic effect; Trauma; Tungsten; Vena Cava Filters; Visualization; X-Ray Computed Tomography; X-Ray Film; Ytterbium; Zirconium; absorption; acute coronary syndrome; animal imaging; biodegradable polymer; biomaterial compatibility; cost; crystallinity; experimental study; flexibility; high risk; imaging modality; imaging properties; imaging study; improved; in vivo; interest; mathematical algorithm; medical implant; metallicity; mortality; nanoparticle; nephrotoxicity; novel; poly-4-dioxan-2-one; porcine model; prevent; prophylactic; radiological imaging; routine imaging; success; time use; venous thromboembolism; zirconium oxide

PROJECT SUMMARY Venous thromboembolism (VTE) is the third most common cardiovascular illness after acute coronary syndrome and stroke. The first line of therapy for VTE is blood thinners; however, these agents are temporarily contraindicated for many at-risk VTE patients, such as those with major trauma and those who undergo complex surgeries, for whom bleeding is a concern. Inferior vena cava (IVC) filters are indicated in this population. Most IVC filters (70%) are intended to be retrieved after their indicated use; however, only 19%- 30% are removed. Unfortunately, complications mount when IVC filters are not removed, which can be very costly ($3,000-$12,000 for filter retrieval and ~$67,000 for treatment of complications). Therefore, resorbable IVC filters were developed, which provide critical protection during their required duration and then simply vanish from the body, thereby alleviating costly removal procedures and downstream complications. However, an important limitation of a resorbable IVC filter system is significant clot burden. Monitoring the absorption time and any significant clot burden with use of imaging techniques would greatly improve the efficacy of deep vein thrombosis treatment. In this study, we will develop of radiopaque absorbable filters that can be routinely imaged to offer a less expensive alternative to assessing filter integrity. Moreover, visualization of the filter under dual-energy computed tomography (DECT) would facilitate discrimination between two or more materials, such as nanoparticles (NPs), iodine, and calcium deposits, which could provide better image quality and quantification of the materials present in the filter. Specifically, we propose to incorporate NPs (made up of gold, bismuth, ytterbium, tantalum, tungsten, barium, and zirconium), into clinically available resorbable polydioxanone (PPDO) suture, investigate the effect of NP infusion within PPDO sutures in terms of mechanical strength, toxicity, and physico-chemical properties over a period of 10 weeks when subjected to human physiological conditions, and perform large animal imaging study using optimized DECT parameters to determine radiopacity, toxicity, and mechanical strength, as well as adverse reactions of image-enhanced suture during necropsies. We will also develop a mathematical algorithm for DECT for the quantification of the different high atomic (Z) number contrast materials infused within the PPDO. Our long-term goal is to develop a totally absorbable IVC filter, inexpensively deployed and monitored by conventional imaging methods that prevents pulmonary embolism for the recommended prophylactic period and then simply vanishes without intervention. The experiments outlined here will be critical to demonstrating the feasibility of using NPs as radiopaque material for DECT imaging embedded within this medical device. Successful development of imaging enhancers for IVC filters may also lead to widespread use of absorbable devices in other cardiovascular and orthopedic applications in which fixtures (such as plates, screws, nails, and rods) are needed only on a temporary basis.

项目摘要 静脉血栓栓塞症（VTE）是继急性冠状动脉粥样硬化性心脏病之后的第三大常见心血管疾病。 综合征和中风。静脉血栓栓塞的第一线治疗是血液稀释剂;然而，这些药物是暂时性的。 禁忌用于许多有风险的VTE患者，如严重创伤患者和接受 复杂的手术，出血是一个问题。下腔静脉（IVC）过滤器适用于这种情况 人口大多数IVC滤器（70%）预期在其预期用途后回收;然而，只有19%- 30%被删除。不幸的是，当IVC过滤器未被移除时，并发症会增加，这可能非常严重。 昂贵（滤器回收费用为3,000 - 12,000美元，并发症治疗费用约为67,000美元）。因此，可吸收 IVC过滤器被开发出来，在其所需的持续时间内提供关键保护，然后简单地 从体内消失，从而减轻昂贵的切除手术和下游并发症。然而，在这方面， 可吸收IVC过滤器系统的一个重要限制是巨大的血栓负担。监测吸收情况 使用成像技术的时间和任何显著的凝块负担将大大提高深部栓塞的疗效。 静脉血栓的治疗 在这项研究中，我们将开发不透射线的可吸收滤器，可以常规成像，以提供 评估过滤器完整性的更便宜的替代方案。此外，可视化的过滤器下的双能量 计算机断层扫描（DECT）将有助于区分两种或多种材料，如 纳米颗粒（NPs）、碘和钙沉积，这可以提供更好的图像质量和定量 过滤器中存在的材料。具体来说，我们建议纳入纳米粒子（由金、铋、 镱、钽、钨、钡和锆），制成临床上可吸收的聚对二氧环己酮 （PPDO）缝线，研究PPDO缝线内NP输注对机械强度的影响， 毒性和物理化学性质，在10周的时间内，当受到人体生理 条件下，并使用优化的DECT参数进行大型动物成像研究，以确定 射线不透性、毒性和机械强度，以及图像增强缝线在 尸检我们还将开发一个数学算法DECT的量化不同的高 注入PPDO内的原子（Z）数造影剂。 我们的长期目标是开发一种完全可吸收的下腔静脉过滤器，廉价部署和监测 通过常规成像方法，在推荐的预防期内预防肺栓塞 然后在没有干预的情况下消失这里概述的实验对于证明 使用NP作为不透射线材料用于嵌入该医疗器械的DECT成像的可行性。 IVC过滤器的成像增强剂的成功开发也可能导致可吸收造影剂的广泛使用。 其他心血管和整形外科应用中的器械，其中固定装置（如板、螺钉、髓内钉和 杆）仅在临时基础上需要。

项目成果

Recent Advances in Nanomedicine for the Diagnosis and Treatment of Prostate Cancer Bone Metastasis.

• DOI: 10.3390/molecules26020384
• 发表时间: 2021-01-13
• 期刊: Molecules (Basel, Switzerland)
• 作者: Hagaman DE;Damasco JA;Perez JVD;Rojo RD;Melancon MP
• 通讯作者: Melancon MP

A novel irinotecan-lipiodol nanoemulsion for intravascular administration: pharmacokinetics and biodistribution in the normal and tumor bearing rat liver.

• DOI: 10.1080/10717544.2020.1869863
• 发表时间: 2021-12
• 期刊: Drug delivery
• 影响因子: 6
• 作者: Melancon MP;Yevich S;Avritscher R;Swigost A;Lu L;Tian L;Damasco JA;Dixon K;Cortes AC;Munoz NM;Liang D;Liu D;Tam AL
• 通讯作者: Tam AL

Localized Perivascular Therapeutic Approaches to Inhibit Venous Neointimal Hyperplasia in Arteriovenous Fistula Access for Hemodialysis Use.

• DOI: 10.3390/biom12101367
• 发表时间: 2022-09-24
• 期刊: Biomolecules
• 影响因子: 5.5

Exploring gold nanoparticle interactions with proteins and the tumor microenvironment in biological systems.

• DOI: 10.21037/tcr.2017.03.53
• 发表时间: 2017-03
• 期刊: Translational cancer research
• 影响因子: 0.9
• 作者: Tian L;Chang A;Melancon MP
• 通讯作者: Melancon MP

Understanding Nanoparticle Toxicity to Direct a Safe-by-Design Approach in Cancer Nanomedicine.

• DOI: 10.3390/nano10112186
• 发表时间: 2020-11-02
• 期刊: Nanomaterials (Basel, Switzerland)
• 作者: Damasco JA;Ravi S;Perez JD;Hagaman DE;Melancon MP
• 通讯作者: Melancon MP