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

基本信息

批准号：
10696996
负责人：
Bryce Beverlin II
金额：
$ 112.75万
依托单位：
QUENCH MEDICAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10696996
关键词：
Address Aerosols Blood Volume Bypass Cancer Etiology Cancer Patient Cells Characteristics Circulation Clinical Clinical Research Combination Drug Therapy Data Deposition Dose Drug Delivery Systems Dryness Effectiveness Electroencephalography Elements Equipment Contamination Excipients Formulation Growth Histologic Human Immunotherapy In Vitro Inhalation Inhalation Toxicology Inhalators Intravenous Investigational Drugs Investigational New Drug Application Lead Leucine Lung Lung Neoplasms Malignant neoplasm of lung Maximum Tolerated Dose Medical Medical Staff Medicine Metabolism Methods National Heart, Lung, and Blood Institute Nebulizer Non-Small-Cell Lung Carcinoma Oncology Operative Surgical Procedures Oral cavity Outcome Pathway interactions Patients Penetration Performance Peripheral Pharmaceutical Preparations Pharmacotherapy Pharyngeal structure Phase Powder dose form Production Research Risk Rodent Rodent Model Route Safety Small Business Innovation Research Grant Sodium Chloride Survival Rate Techniques Technology Testing Therapeutic Toxicokinetics Toxicology Translations Treatment outcome Tumor Burden Tumor Tissue United States Food and Drug Administration United States National Institutes of Health Universities Virginia Wettability Work chemotherapy commercialization drug development efficacy study first-in-human gemcitabine good laboratory practice improved in vivo innovation manufacture meter mortality novel particle pre-clinical preclinical study scale up side effect standard of care systemic toxicity targeted delivery translational potential tumor

项目摘要

Project Summary / Abstract Significance Lung cancer is the leading cause of cancer mortality with a 5-year survival rate of less than 20% following standard of care therapy. Problem Despite the use of aggressive surgery, combination chemotherapy and immunotherapy, a major limitation in the control of primary and metastatic non-small cell pulmonary tumors with the use of the systemic administration of 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 be 1) scale-up the lead Quench EEG formulation and conduct characterization, stability, and performance studies, and 2) conduct IND-enabling toxicology studies in an established inhalation toxicology rodent model for regulatory submission. 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.

项目摘要 /摘要意义肺癌是癌症死亡率的主要原因，其5年生存率少于20％护理疗法标准。问题尽管使用了侵略性手术，联合化疗和免疫疗法，但在控制原发性和转移性非小细胞肺肿瘤，并使用全身给药由于血容量稀释和代谢，药物是肺部药物浓度的低浓度。有关键未满足的医疗需要制定新的策略来改善患者治疗结果。创新与全身递送化学疗法相反，吸入将化学治疗药物直接提供给肿瘤肺中的组织由于局部药物浓度增加而增强其功效和安全性肺部，循环中系统性药物水平降低，全身毒性降低。差距使用雾化化学疗法药物的初步临床前体内研究表明有效性和确定了通过气溶胶递送的可行性，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围气道渗透，高喉咙沉积，污染设备，以及向医务人员的附带气溶胶风险。项目目标为了解决这些缺点，我们正在开发一种通过吸入直接到达肺部肿瘤，以最大程度地提高气溶胶的有效性和安全性用标准剂量的一小部分治疗。我们将创建一种新型的干粉化学治疗配方含有FDA批准的化学疗法药物治疗非小细胞肺癌。目标该提案的目的是1）扩大铅淬灭脑脑图和行为表征，稳定性，和绩效研究，以及2）在已建立的吸入毒理学中进行毒理学研究啮齿动物模型的监管提交模型。商业潜力将该技术转换为临床上有益的吸入化学疗法产品有可能通过提供针对性较低的肺癌患者的肺肿瘤的治疗显着改善直接对肺部的药物剂量，同时最大程度地减少全身毒性。