Water-based liquid embolic agent for the treatment of vascular rich tumors

AquaTeX Medical正在开发一种新型液体栓塞剂(LEM)--Aqua Embolic System(AES)--以 提高癌症治疗水平。经皮血管栓塞术是为阻断高血管肿瘤的供血血管而设计的 与其他经动脉栓塞术(TAE)材料相比，该材料具有良好的疗效和良好的生物相容性。 TAE是一种基于导管的治疗多血管肿瘤的方法。栓塞剂是通过一个小的 放置在动脉中的导管阻塞血管，因缺血而导致细胞死亡。TAE治疗的必要性 正在快速增长，预计2025年其市场预测将达到21.64亿美元。目前，微粒 是TAE最常用的栓塞剂。尽管微粒被广泛使用，但它们也有自己的 局限性，例如，1)由于聚集效应或每个组织的相对较大的尺寸而导致的次优组织渗透率 颗粒，2)处理后血管不完全闭塞导致较高的再通率(16-%)，3)缺乏 在需要添加造影剂的x射线下的可见性，以及4)无法加载许多电流 化疗药物或免疫活性分子。因此，迫切需要更好的 栓塞剂。另一方面，LEM具有1)卓越的组织穿透性，2)实现 靶血管永久性闭塞；3)透视下能见度好。然而，FDA并没有 尚未批准任何LEM用于治疗多血管肿瘤，原因是与强大的粘附性相关的安全性问题 或目前市场上LIMs中的有机溶剂引起的组织毒性。 为了克服这些限制，我们开发了第一台名为AES的单组分水基LEM。 AES是一种透明的水溶液，由生物相容的多糖组成。它被钙离子激活 在血液中，并形成固体水凝胶铸型，显示出良好的组织渗透性。以其独特的粘度- 控制技术，AES可以通过目前可用的最小单腔微导管输送 系统。它不含有毒有机溶剂，而且，俄歇电子能谱的主要成分已广泛 经FDA批准，用于细胞培养基及食品添加剂。我们的初步动物实验显示 AES的一致疗效和生物兼容性。 这个第一阶段STTR项目的主要目标是：1)在兔子身上确认AES的有效性 高血管肿瘤模型，历史上一直用于栓塞剂的临床前评估 FDA批准，以及2)使用非肿瘤肝脏评估长期安全性、持久性和生物相容性 动脉栓塞术模型。Embozene®，这是一种目前用于临床的微粒产品， 被用作比较(商业对照)。 在我们随后的第二阶段SBIR/STTR项目中，我们将继续进行调查所需的下一步测试 设备豁免(IDE)批准，随后进行了第一项人体研究。我们的最终目标是提高安全性 高血管肿瘤患者行TAE治疗的疗效。

AquaTeX Medical is developing a novel liquid embolic material (LEM) - Aqua Embolic System (AES) - to improve cancer treatment. AES is designed to occlude feeding vessels of hypervascular tumors with superior efficacy and excellent biocompatibility as compared to other trans-arterial embolization (TAE) materials. TAE is a catheter-based treatment to treat hypervascular tumors. Embolic materials are injected via a small catheter placed in the artery occluding the vessels, causing cell death by ischemia. The need for TAE treatment is rapidly growing, and its market forecast is expected to reach $2.164 billion in 2025. Currently, microparticles are the most commonly used embolic materials for TAE. Despite their wide use, microparticles have their limitations, e.g.,1) sub-optimal tissue penetration due to clumping effects or the relatively large size of each particle, 2) incomplete occlusion of the treated vessel leading to high recanalization rate (16-64%), 3) lack of visibility under x-ray requiring the addition of contrast medium, and 4) inability to load many current chemotherapeutic drugs or immunologically active molecules. Therefore, there is a strong need for better embolic materials. LEMs, on the other hand, have 1) superior tissue penetration, 2) capability to achieve permanent occlusion of the target vessels, and 3) good visibility under fluoroscopy. However, the FDA has not yet approved any LEMs to treat hypervascular tumors, due to safety concerns related to the strong adhesiveness or tissue toxicity caused by the organic solvents in current LEMs on the market. To overcome these limitations, we have developed the first single-component water-based LEM called AES. AES is a clear aqueous solution composed of biocompatible polysaccharides. It is activated by the calcium ions in the blood and forms a solid hydrogel cast that shows excellent tissue penetration. With its unique viscosity- controlling technology, AES can be delivered via the currently available smallest single-lumen microcatheter system. It contains no toxic organic solvents, and moreover, the main compositions of the AES have been widely used for cell culture medium and food additives with FDA approval. Our preliminary animal experiments showed consistent efficacy and biocompatibility of the AES. The primary goal of this Phase I STTR project is 1) to confirm the efficacy of the AES using a rabbit hypervascular tumor model, which has been historically used for preclinical evaluation of embolic materials for FDA approval, and 2) to evaluate long-term safety, durability, and biocompatibility using a non-tumor hepatic artery embolization model. Embozene®, which is a micro-particle product currently used in the clinical practice, is used as comparison (commercial control). In our subsequent Phase II SBIR/STTR project, we will pursue the next step of testing needed for investigational device exemption (IDE) approval, followed by the first-in-human study. Our final goal is to improve the safety and efficacy of TAE procedures performed for patients with hypervascular tumors.