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

点击翻译按钮获取中文摘要

 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.