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

据估计，外周动脉疾病（PAD）影响全世界超过2亿人，而且这个数字还在不断增加。带或不带支架的血管内介入是首选治疗选择。最近的随机对照临床试验证明了药物涂层球囊（DCB）治疗在改善通畅性方面优于无涂层球囊。在许多临床病例中，DCB器械提供了药物洗脱支架（DES）的替代方案，同时也：1。避免永久性植入2\。短期用药3\。避免额外的/多个支架层。通常，紫杉醇-DCB是首选的器械，但器械在药物剂量、赋形剂选择和整体涂层配方方面有所不同。这种方法的有效性的主要挑战是有效地将药物递送到靶病变，以及药物在血管壁中以治疗水平保留足够长的时间以进行愈合。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下降到标称1 μ g/ml治疗极限以下。为了防止再狭窄和血栓形成，并促进愈合，药物应保留在动脉血管壁中至少30天，理想情况下，最多90天。随着药物被冲洗到血液中，市场上的许多DCB迅速下降到这个水平以下。虽然单药DCB利用一种治疗方法，通常用于预防再狭窄，但血管愈合是一个复杂的多阶段过程，这种未满足的需求促使Arterius开发了一种替代药物，即一种新型的双药DCB，使用抗增殖药物来预防血管再狭窄。早期阶段，和抗血栓形成和促进血管愈合的后期阶段。使用Arterius独特的专利赋形剂和双药制剂，初步研究显示，在离体和体内模型中，紫杉醇和西罗莫司的治疗极限均为1 μ g/ml，这似乎没有合理的科学依据。了解这些药物对动脉组织细胞的剂量依赖性效应对于实现有效剂量至关重要。使用这种方法开发下一代DCB将增加重要的市场机会，补充Arterius目前的生物可吸收血管支架项目。它将潜在地降低外周动脉疾病患者截肢和死亡的风险，并降低NHS的药物成本。

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.