Development of multifunctional biodegradable drug-loaded polymer stents for inoperable esophageal malignancies

开发用于不能手术的食管恶性肿瘤的多功能可生物降解载药聚合物支架

• 批准号: 9023017
• 负责人: Yunqing Kang
• 金额: $ 7.1万
• 依托单位: FLORIDA ATLANTIC UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-13 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9023017
• 关键词: 3D Print; Affect; Animal Model; Antineoplastic Agents; Chest Pain; Clinical; Complication; Deglutition Disorders; Detection; Development; Disease; Elasticity; Esophageal; Esophageal Neoplasms; Esophagus; Esters; Excision; Family suidae; Foundations; Future; Goals; Graph; Growth; Hemorrhage; In Vitro; Local Therapy; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of esophagus; Measures; Mechanics; Medical; Metals; Modeling; Natural regeneration; Neoplasm Metastasis; Obstruction; Operative Surgical Procedures; Outcome Study; Paclitaxel; Palliative Care; Patients; Perforation; Performance; Pharmaceutical Preparations; Phase; Polymers; Property; Refractory; Research; Risk; Stents; Stomach; Structure; Survival Rate; Techniques; Testing; Therapeutic; Time; Tissue Engineering; Translational Research; Tubular formation; Tumor Tissue; Unresectable; Urethane; biodegradable polymer; biomaterial compatibility; cancer cell; cancer therapy; cell growth; design; elastomeric; grasp; improved; in vitro testing; in vivo; migration; mortality; neoplastic cell; novel; palliation; poly(lactic acid); prevent; public health relevance; research study; treatment choice; tumor

 DESCRIPTION (provided by applicant): Esophageal cancer is the sixth most common form of cancer worldwide. The treatment for esophageal cancer remains a major medical challenge. 5-year survival rate of these patients remain very low, less than 15%. Despite improvements in surgical techniques, 50% to 60% of patients are not suitable for surgery at the time of presentation due to late tumor detection or unresectable metastases. For these patients, only palliative therapy is possible. The treatment option is to relieve dysphagia. Currently, self-expanding metal stents (SEMS) have been used in the palliation of patients with malignant esophageal obstruction. However, application of these stents has revealed complications, such as bleeding and perforation of esophagus, chest pain, and stent's migration into the stomach. Among these complications, migration is the most common one. Additionally, these stents are composed of metallic wires and are unable to carry and deliver anti-cancer drugs to treat esophageal tumors and prevent tumor tissue ingrowth. Currently, there are no stents available in a clinical setting, which have the ability of preventing or decreasing the complication of migration and at the same time provide the capability of delivering cancer therapy drugs. To overcome the above problems, in this study we propose to develop new biodegradable elastic polymer stents loaded with anti-cancer drugs for treating patients with inoperable esophageal malignancies. We will use biodegradable elastomeric polymer poly(ester- urethane) (PEU) and crystalline poly(lactic acid) (PLA) as a matrix to produce elastic, yet sufficiently stiff adjustabe esophagus stents for decreasing complications. We will design a geometrical feature called an upward spiral groove structure on the outside of the stent that resists migration. To provide anti-cancer potency, we will load the stents with anti-cancer drug paclitaxel (PTX). We propose to use a 3D printing technique to fabricate the PTX-PEU/PLA stents. We hypothesize that 1) the biodegradable elastic PEU/PLA stent with upward spiral grooves will significantly increase the anti-migration force and prevent the stent's slippage; 2) the biodegradable PTX-PEU/PLA will have the ability to release PTX for sustained inhibition on the growth of esophagus cancer cells in vitro. To test these hypotheses, we propose the following specific aims: Aim 1) Fabricate PEU/PLA tubular stents with upward spiral grooves and characterize the physicochemical properties, anti-migration property, and biocompatibility. Aim 2) Fabricate PTX-PEU/PLA stents with upward spiral grooves and characterize their inhibition ability on the growth of esophageal cancer cells in vitro. For PTX-PEU/PLA stents, we will characterize drug release profile in vitro and inhibition ability of the stents on esophageal tumor cell growth. The novel PTX-PEU/PLA drug-loaded stents with upward spiral grooves hold a promising potential for the treatment of patients with inoperable esophageal malignancies. A successful outcome for this study could have a wider impact on the treatment of esophageal cancer and the need for tissue-engineered stents for esophagus regeneration after surgical removal.

 描述（由适用提供）：食管癌是全球癌症的第六种最常见形式。食管癌的治疗仍然是一个主要的医疗挑战。这些患者的5年生存率仍然很低，小于15％。尽管手术技术有所改善，但由于晚期肿瘤检测或不可切除的转移，有50％至60％的患者在出现时不适合手术。对于这些患者，只有姑息治疗。治疗选择是减轻吞咽困难。当前，自我膨胀的金属支架（SEM）已用于恶性食管物镜的患者的抑制。然而，这些支架的应用揭示了并发症，例如食管，胸痛以及支架迁移到摊位中的并发症。在这些并发症中，迁移是最常见的。此外，这些支架由金属电线组成，无法携带和输送抗癌药物来治疗食管肿瘤并预防肿瘤组织。当前，在临床环境中没有可用的支架，它们具有预防或减少迁移并发症的能力，同时提供了提供癌症治疗药物的能力。为了克服上述问题，在这项研究中，我们建议开发新的可生物降解的弹性聚合物支架，这些弹性聚合物支架上装有抗癌药物，用于治疗无法使用的食管恶性肿瘤患者。我们将使用可生物降解的弹性弹性聚合物聚合物聚（PEU）（PEU）和晶体聚（乳酸）（PLA）作为基质，以产生弹性，但足够硬的可调节食管支架，以减少并发症。我们将设计一个几何特征，称为支架外部的向上螺旋凹槽结构，以抵抗迁移。为了提供抗癌效力，我们将用抗癌药物紫杉醇（PTX）加载支架。我们建议使用3D打印技术来制造PTX-PEU/PLA支架。我们假设1）具有向上的螺旋凹槽的可生物降解的弹性PEU/PLA支架将显着增加抗移民力并防止支架的滑动； 2）可生物降解的PTX-PEU/PLA将具有释放PTX的能力，以持续抑制食管癌细胞在体外的生长。为了检验这些假设，我们提出了以下特定目的：目标1）用具有向上的螺旋凹槽的PEU/PLA管状支架来表征物理特性，抗移民特性和生物相容性。 AIM 2）用向上的螺旋凹槽制造PTX-PEU/PLA支架，并表征其对食管癌细胞在体外生长的抑制能力。对于PTX-PEU/PLA支架，我们将在体外释放药物释放特征和支架对食管肿瘤细胞生长的抑制能力。具有向上螺旋凹槽的新型PTX-PEU/PLA药物载有支架，有望治疗无法手术性食管恶性肿瘤的患者。这项研究的成功结果可能会对食管癌的治疗产生广泛的影响，并且需要在手术切除后对食管再生进行组织工程的支架。