In-Vitro evaluation of the effectiveness of a novel Dual Drug Coated Balloon catheter to treat Vascular and cardiovascular diseases

新型双药物涂层球囊导管治疗血管和心血管疾病有效性的体外评估

• 批准号: 10109618
• 金额: $ 12.47万
• 依托单位: ARTERIUS LIMITED
• 依托单位国家: 英国
• 项目类别: Launchpad
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10109618
• 关键词: Vitro; evaluation; effectiveness; novel; Dual

Peripheral arterial disease (PAD) is estimated to affect over 200 million people around the world and this number is increasing continuously. Endovascular interventions with or without stenting are among the preferred treatment choices. Recent randomised controlled clinical trials have demonstrated the superiority of drug-coated balloon (DCB) therapy compared to uncoated balloon, in terms of improved patency. In many clinical cases, DCB devices offer an alternative to Drug-Eluting Stents (DES), while also:1\. Avoiding a permanent implant2\. Shorter medications3\. Avoiding additional/multiple stent layers.Generally, paclitaxel-DCB are the device of choice, but devices differ in terms of drug dosing, the selection of the excipient and the overall coating formulation. The main challenges in the effectiveness of this approach are the efficient delivery of drug to the target lesion and retention of drug in the vessel wall at therapeutic levels long enough for healing to occur. For current paclitaxel-DCBs, as much as 90% of drug is lost in the blood stream, with only between 1-10% successfully delivered. Furthermore, drug concentration in tissue rapidly drops below the nominal 1ug/ml therapeutic limit. To prevent restenosis and thrombosis, and promote healing, the drugs should be retained in the arterial vessel wall for a minimum of 30-days and, ideally, up to 90-days. Many DCBs on the market rapidly fall below this level as drug is washed into the bloodstream.While single-drug DCBs utilise one therapeutic, generally to prevent restenosis, vascular healing is a complex multi-stage process, with a different drug required in the latter stages to the early stages of healing.This unmet need has encouraged Arterius to develop an alternative a novel dual drug DCB using antiproliferative to prevent restenosis in the early stages, and an antithrombotic and promote vascular healing in the later stages. Using Arterius' unique and patented excipient and dual drug formulation, preliminary work has shown good performance delivering drugs to the tissues in ex-vivo and in-vivo models.The oft-quoted therapeutic limit of 1ug/ml for both paclitaxel and sirolimus does not appear to have sound scientific basis. Understanding the dose-dependent effects of these drugs on the cells of the arterial tissue is essential to achieve effective dosage.Development of next-generation DCB using this approach would add a significant market opportunity, complimentary to Arterius current bioresorbable vascular stent programmes. It will potentially reduce the risk of amputation and death in peripheral artery disease patients and reduce medication costs for the NHS.

估计外围动脉疾病（PAD）估计会影响全球超过2亿人，并且这一数字不断增加。有或没有支架支架的血管内干预是首选的治疗选择。最近的随机对照临床试验表明，与未涂层的气球相比，在提高通畅方面，药物包被的球囊（DCB）疗法的优势。在许多临床情况下，DCB设备提供了替代药物洗脱支架（DES）的替代方案，而：1 \。避免永久植入2 \。较短的药物3 \。避免其他/多个支架层。从基础上讲，紫杉醇-DCB是选择的装置，但是设备在药物给药方面有所不同，赋形剂的选择和整体涂料配方。这种方法有效性的主要挑战是在治疗水平下有效地将药物递送到靶病变和在血管壁中保留的治疗水平，足以进行愈合。对于当前的紫杉醇-DCB，多达90％的药物在血液中丢失，仅成功递送了1-10％。此外，组织中的药物浓度迅速降至标称1ug/mL治疗限制以下。为了防止再狭窄和血栓形成并促进愈合，应将药物保留在动脉血管壁中至少30天，理想情况下，最多90天。由于将药物洗净到血液中，因此市场上的许多DCB迅速降至该水平以下。虽然单药DCB使用一种治疗性，通常可以防止再狭窄，但血管愈合是一个复杂的多阶段过程，在后期阶段需要不同的药物，而在早期的阶段需要疗养的早期疗法。在早期阶段再狭窄，抗血栓形成并在后期促进血管愈合。使用Arterius独特的专利赋形剂和双重药物配方，初步的工作表明，在前体体和体内模型中为组织提供了良好的性能。经常引用的paclitaxel和Sirolimus的1UG/ML的治疗限制似乎没有合理的科学基础。了解这些药物对动脉组织细胞的剂量依赖性作用对于实现有效剂量至关重要。使用这种方法的下一代DCB的开发将增加大量的市场机会，这是Arterius当前可生物可吸收的血管支架程序的补充。它可能会减少周围动脉疾病患者截肢和死亡的风险，并降低NHS的药物成本。