Mechanisms of drug-coated balloon therapy

药物涂层球囊治疗的机制

基本信息

批准号：
10686919
负责人：
Vijaya B. Kolachalama
金额：
$ 57.16万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
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 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10686919
关键词：
Acute Angioplasty Arterial Fatty Streak Arteries Atherosclerosis Balloon Angioplasty Biophysics Catheters Chemicals Clinical Clinical effectiveness Communities Data Device Designs Devices Dexamethasone Drug Delivery Systems Drug Kinetics Drug Modelings Drug Modulation Drug Utilization Drug usage Emerging Technologies Engineering Environmental Risk Factor Excipients FDA approved Fluorescence Formulation Fracture Future Generations Goals Implant Inflammation Intervention Lead Lesion Link Measures Mechanics Meta-Analysis Metals Modeling Modification Molecular Morphology Optical Coherence Tomography Oryctolagus cuniculus Outcome Ozone Paclitaxel Patients Performance Peripheral arterial disease Permeability Pharmaceutical Preparations Physicians Physiological Prevalence Property Publications Publishing Randomized, Controlled Trials Role Safety Stents Structure Surface Technology Testing Tissues Treatment Protocols United States Urea Work aging population biomaterial compatibility biophysical model clinical translation coronary vasculature critical limb Ischemia design drug release kinetics experience follow-up high risk hydrophilicity improved in vivo in vivo Model insight interfacial limb amputation limb loss mechanical force mortality next generation novel novel drug class novel therapeutics pre-clinical preclinical development predictive modeling randomized trial response restenosis standard of care structural imaging systemic toxicity ultrasound uptake

项目摘要

PROJECT SUMMARY Drug-coated balloons (DCBs) have evolved as a promising interventional strategy for peripheral arterial disease (PAD). While paclitaxel (PTX)-based DCBs were emerging as the interventional standard of care for many PAD lesions, a recent meta-analysis of randomized trials suggested excess late mortality in PTX-treated patients. This result prompted the FDA to issue a warning that ultimately led to a marked reduction of the clinical use of DCBs. This response by the clinical and regulatory communities underscores a need to develop next-generation DCBs that could show improved efficacy and safety profiles. Drawing from our previous experience related to studies on drug-eluting stents and more recently on DCBs, we propose two hypothesis- driven design strategies to enhance DCB performance and safety. Aims I and II will consider balloon surface hydrophilicity and coating composition, respectively, as critical DCB design variables, and seek to identify mechanistic relations between these design variables, coating microstructure, drug delivery efficacy, as well as local and systemic toxicity. We will predict optimal DCB designs for both acute and sustained drug delivery using a biophysical contact model that computes deterministic interfacial mechanical interactions during DCB deployment. Our material design space includes two excipients (urea and shellac) and two drugs (PTX and dexamethasone (DEX)), with consideration of variable excipient-drug ratios and novel balloon pre-treatment protocols prior to coating applications. We will use an in vivo model of rabbit atherosclerosis to evaluate optimized DCBs, providing support for our approach to enhance PTX delivery and insight into the clinical potential of DEX as an alternate DCB payload.

项目摘要涂有药物的气球（DCB）已进化为外围动脉的有前途的干预策略疾病（PAD）。而基于紫杉醇（PTX）基于DCB的DCB正在成为介入的护理标准许多PAD病变，最近对随机试验的荟萃分析表明，PTX治疗的过度死亡率过高患者。该结果促使FDA发出警告，最终导致明显减少 DCB的临床使用。临床和监管社区的这种反应强调了发展下一代DCB可以显示出提高的功效和安全性概况。从我们以前的与毒品洗脱支架的研究以及最近有关DCB的研究有关的经验，我们提出了两个假设 - 驱动的设计策略以提高DCB性能和安全性。目标I和II会考虑气球表面分别作为关键DCB设计变量，分别为亲水性和涂料组成，并试图识别这些设计变量，涂料微结构，药物输送功效以及局部和全身毒性。我们将预测急性和持续药物输送的最佳DCB设计使用在DCB期间计算确定性界面机械相互作用的生物物理接触模型部署。我们的材料设计空间包括两种赋形剂（尿素和虫胶）和两种药物（PTX和地塞米松（DEX）），考虑可变的散发器比率和新型气球预处理涂料应用程序之前的协议。我们将使用兔动脉粥样硬化的体内模型评估优化的DCB，为我们增强PTX交付和深入了解临床的方法提供了支持 DEX作为替代DCB有效载荷的潜力。