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

外周动脉疾病（PAD）估计影响全球超过2亿人，并且这一数字还在不断增加。血管内介入治疗伴或不伴支架置入是首选的治疗选择。最近的随机对照临床试验表明，药物包被球囊（DCB）治疗在改善通畅方面优于非包被球囊。在许多临床病例中，DCB装置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。短medications3 \。避免额外/多个支架层。一般来说，紫杉醇- dcb是首选的设备，但设备在给药剂量，赋形剂的选择和整体涂层配方方面有所不同。这种方法有效性的主要挑战是有效地将药物输送到目标病变，并在血管壁中保留足够长的治疗水平以发生愈合。对于目前的紫杉醇- dcbs，高达90%的药物在血液中丢失，只有1-10%的药物成功递送。此外，组织中的药物浓度迅速下降到标称的治疗极限1ug/ml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上保留至少30天，理想情况下，最长可达90天。随着药物进入血液，市场上的许多dcb迅速降至这一水平以下。虽然单药dcb通常使用一种治疗方法，以防止再狭窄，但血管愈合是一个复杂的多阶段过程，在愈合的后期和早期阶段需要不同的药物。这一未满足的需求促使Arterius公司开发一种替代方案，一种新型双药DCB，在早期使用抗增殖药物预防再狭窄，在后期使用抗血栓药物并促进血管愈合。利用Arterius独有的专利赋形剂和双药配方，前期工作已在离体和体内模型中显示出良好的给药性能。常被引用的紫杉醇和西罗莫司的治疗限度均为1ug/ml，似乎没有可靠的科学依据。了解这些药物对动脉组织细胞的剂量依赖性对获得有效剂量至关重要。使用这种方法开发下一代DCB将增加重要的市场机会，与Arterius目前的生物可吸收血管支架项目互补。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的药物费用。

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.