Treating non-small cell lung tumors with a novel inhaled dry powder chemotherapeutic formulation

项目摘要/摘要 意义肺癌是癌症死亡的主要原因，5年生存率为16%，仅次于 手术和静脉化疗。 尽管使用了积极的手术和联合化疗，但这是控制的一个主要限制 应用全身给药治疗原发和转移性非小细胞肺癌 化疗药物是指由于血液容量稀释和新陈代谢而在肺部的低浓度药物。 有一个严重的未得到满足的医疗需求，即开发新的战略来改善患者的治疗结果。 创新与全身给药不同，吸入给药是一种化疗药物 由于增加了局部用药，直接转移到肺内的肿瘤组织从而增强了其疗效和安全性 在肺中的浓度，降低循环中的全身药物水平，并降低全身毒性。 使用雾化化疗药物的GAP初步临床前体内研究显示了疗效和 确定了通过气雾剂给药的可行性，但有毒药物的雾化有重大缺陷。这些 缺点包括缺乏有效的外周呼吸道穿透，口咽喉沉积高，污染 设备的风险，以及附带的气雾剂风险给医务人员。 项目目标为了解决这些缺点，我们正在开发一种新的方法来交付 通过吸入化疗药物直接到达肺肿瘤，以最大限度地发挥疗效 标准剂量的一小部分气雾剂治疗的安全性。我们将创造一种新型的干粉 含有FDA批准的化疗药物的化疗制剂，用于治疗非 小细胞肺癌。 这项提案的目的是评估制造新配方的可行性，然后 在已建立的体内肺癌模型中展示有效性。 将这项技术转化为临床有益的吸入性化疗产品的商业潜力 有可能显著改善肺癌患者的治疗，通过提供 有针对性地将较低剂量的药物直接注入肺部，同时将全身毒性降至最低。

Project Summary / Abstract Significance Lung cancer is the leading cause of cancer mortality with a 5-year survival rate of 16% following surgery and intravenous chemotherapy. Problem Despite the use of aggressive surgery and combination chemotherapy, a major limitation in the control of primary and metastatic non-small cell pulmonary tumors with the use of the systemic administration of chemotherapy drugs is the low drug concentration in the lungs due to blood volume dilution and metabolism. There is a critical unmet medical need to develop new strategies to improve patient treatment outcomes. Innovation In contrast to systemic delivery of chemotherapy, inhalation delivers a chemotherapeutic drug directly to tumor tissues in the lung thereby enhancing its efficacy and safety due to increased local drug concentration in the lung, decreased systemic drug levels in the circulation, and decreased systemic toxicity. Gap Preliminary pre-clinical in-vivo studies using nebulized chemotherapy drugs has demonstrated efficacy and established the feasibility of delivery via aerosol, but nebulization of toxic drugs has major drawbacks. These drawbacks include a lack of efficient peripheral airway penetration, high mouth-throat deposition, contamination of equipment, and collateral aerosol risk to medical staff. Project Objective To address these drawbacks, we are developing a new method of delivering a chemotherapeutic drug via inhalation to reach pulmonary tumors directly in order to maximize the effectiveness and safety of the aerosol treatment with a fraction of the standard dose. We will create a novel dry powder chemotherapeutic formulation containing an FDA approved chemotherapy medication for the treatment of non- small cell lung cancer. Aims Aims of this proposal will evaluate the feasibility of manufacturing the novel formulation and then demonstrating efficacy in an established in-vivo lung cancer model. Commercial Potential Translation of this technology into a clinically beneficial inhalable chemotherapy product has the potential to significantly improve the treatment of pulmonary tumors in lung cancer patients by delivering targeted lower doses of medicine directly to the lung while minimizing systemic toxicity.