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

用新型吸入干粉化疗制剂治疗非小细胞肺肿瘤

• 批准号: 10080226
• 负责人: Bryce Beverlin II
• 金额: $ 40万
• 依托单位: QUENCH MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-14 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080226
• 关键词: Address; Aerosols; Alveolar; Benchmarking; Blood Circulation; Blood Volume; Bypass; Cancer Etiology; Cancer Model; Cancer Patient; Cells; Characteristics; Clinical; Clinical Research; Combination Drug Therapy; Custom; Data; Data Analyses; Deposition; Dose; Drug Delivery Systems; Effectiveness; Electroencephalography; Equipment Contamination; Excipients; FDA approved; Formulation; Future; Goals; Gold; Grant; Growth; Histopathology; Human; In Vitro; Inhalation; Inhalators; Intravenous; Investigational Drugs; Lead; Leucine; Lung; Lung Neoplasms; Malignant neoplasm of lung; Mannitol; Medical; Medical Staff; Medicine; Metabolism; Methods; Microscopic; National Heart, Lung, and Blood Institute; Nebulizer; Non-Small-Cell Lung Carcinoma; Nonmetastatic; Oncology; Operative Surgical Procedures; Oral cavity; Organ; Outcome; Particle Size; Patients; Penetration; Peripheral; Pharmaceutical Preparations; Pharmacologic Substance; Pharyngeal structure; Phase; Powder dose form; Process; Production; Research; Respiratory System; Risk; Rodent; Rodent Model; Safety; Small Business Innovation Research Grant; Sodium Chloride; Survival Rate; Technology; Testing; Tissues; Toxicology; Translations; Treatment outcome; Tumor Burden; Tumor Tissue; United States National Institutes of Health; Universities; Virginia; Weight; Wettability; Work; base; chemotherapy; clinical toxicology; efficacy study; efficacy testing; first-in-human; gemcitabine; improved; in vivo; innovation; meetings; mortality; novel; particle; pre-clinical; side effect; success; systemic toxicity; targeted delivery; targeted treatment; tumor

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.

项目总结/摘要 肺癌是癌症死亡的主要原因，5年生存率为16%， 手术和静脉化疗。 尽管使用了积极的手术和联合化疗，但控制肿瘤的一个主要限制是， 原发性和转移性非小细胞肺肿瘤的治疗， 化疗药物是由于血容量稀释和代谢导致的肺部药物浓度低。 有一个关键的未满足的医疗需求，以开发新的战略，以改善患者的治疗结果。 创新与全身化疗不同，吸入化疗药物 直接作用于肺中的肿瘤组织，从而由于增加了局部药物浓度而提高了其功效和安全性。 降低了肺中的药物浓度，降低了循环中的全身药物水平，并降低了全身毒性。 使用雾化化疗药物的初步临床前体内研究已经证明了疗效， 建立了通过气雾剂递送的可行性，但是有毒药物的雾化具有主要缺点。这些 缺点包括缺乏有效的外周气道渗透、高的口-喉沉积、污染 以及对医务人员的附带气溶胶风险。 项目目标为了解决这些缺点，我们正在开发一种新的方法， 化疗药物通过吸入直接到达肺部肿瘤，以最大限度地发挥疗效 和使用标准剂量的一部分的气雾剂治疗的安全性。我们将创造一种新的干粉 在一些实施方案中，本发明提供了含有FDA批准的用于治疗非肿瘤的化疗药物的化疗制剂。 小细胞肺癌 本提案的目的是评估生产新配方的可行性， 在已建立的体内肺癌模型中证明了功效。 将该技术转化为临床有益的可吸入化疗产品的商业潜力 通过给药，具有显著改善肺癌患者肺肿瘤治疗的潜力， 将较低剂量的药物直接靶向肺部，同时将全身毒性降至最低。