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.

据估计，全世界有超过 2 亿人患有外周动脉疾病 (PAD)，而且这个数字还在不断增加。带或不带支架的血管内干预是首选治疗选择之一。最近的随机对照临床试验证明，与未涂层球囊相比，药物涂层球囊 (DCB) 疗法在改善通畅性方面具有优越性。在许多临床案例中，DCB 装置提供了药物洗脱支架 (DES) 的替代方案，同时还：1\。避免永久植入2\。较短的用药时间3\.避免额外/多个支架层。通常，紫杉醇-DCB是首选装置，但装置在药物剂量、赋形剂的选择和总体涂层配方方面有所不同。这种方法有效性的主要挑战是如何将药物有效递送至目标病变，以及将药物以治疗水平保留在血管壁中足够长的时间以实现愈合。对于目前的紫杉醇-DCB，多达 90% 的药物在血流中损失，只有 1-10% 成功递送。此外，组织中的药物浓度迅速降至标称的 1ug/ml 治疗极限以下。为了防止再狭窄和血栓形成并促进愈合，药物应在动脉血管壁中保留至少 30 天，理想情况下最多保留 90 天。随着药物被冲入血液中，市场上的许多 DCB 会迅速降至该水平以下。虽然单药 DCB 使用一种治疗方法，通常是为了防止再狭窄，但血管愈合是一个复杂的多阶段过程，后者需要不同的药物这种未满足的需求促使 Arterius 开发出一种新型双药 DCB 替代方案，在早期阶段使用抗增殖剂预防再狭窄，在后期使用抗血栓剂并促进血管愈合阶段。使用 Arterius 独特的专利赋形剂和双药物配方，初步工作已显示出在离体和体内模型中将药物输送到组织的良好性能。紫杉醇和西罗莫司经常引用的 1ug/ml 治疗限值并不适用。似乎有充分的科学依据。了解这些药物对动脉组织细胞的剂量依赖性影响对于实现有效剂量至关重要。使用这种方法开发下一代 DCB 将增加一个重要的市场机会，与 Arterius 目前的生物可吸收血管支架项目相辅相成。它将有可能降低外周动脉疾病患者截肢和死亡的风险，并降低 NHS 的药物费用。