Nanoparticle Generator for Animal Inhalation Experiments

用于动物吸入实验的纳米颗粒发生器

• 批准号: 7219038
• 负责人: AMIR A NAQWI
• 金额: $ 39.72万
• 依托单位: POWERSCOPE, INC
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7219038
• 关键词: A/J Mouse; Acoustics; Adenocarcinoma; Aerosols; Air; Albuterol Sulfate; Animal Model; Animals; Back; Biodistribution; Breathing; Budgets; Caliber; Characteristics; Chemopreventive Agent; Clinical; Clinical Trials; DL-alpha-Difluoromethylornithine; Deposition; Depth; Development; Devices; Diffusion; Dose; Drops; Drug Delivery Systems; Drug Evaluation; Electronics; Excision; Film; Frequencies; Future; Generations; Hamsters; Human; Inhalation Therapy; Learning; Liquid substance; Lung; Lung Adenocarcinoma; Medical; Modeling; Mus; Nebulizer; Non-Small-Cell Lung Carcinoma; Numbers; Particle Size; Penetration; Peripheral; Personal Satisfaction; Pharmaceutical Preparations; Phase; Powder dose form; Production; Purpose; Radioactive; Range; Respiratory System; Safety; Scientist; Solutions; Source; Squamous cell carcinoma; Standards of Weights and Measures; Supportive care; Surface; Technology; Testing; Time; Transducers; Ultrasonic Transducer; Ultrasonics; United States Food and Drug Administration; Ventilator; Water; Work; aqueous; base; cancer therapy; chemotherapeutic agent; commercialization; concept; density; desire; docetaxel; drug inhalation; falls; interest; nano; nanoparticle; particle; prevent; prototype; research study; response; size; submicron

DESCRIPTION (provided by applicant): A general-purpose turnkey drug nanoparticle generator (DNG) is planned to be developed in this project. An immediate application of such a particle generator is to test new inhalable drugs in animal models. Most animal models for inhalation therapy, like mice and hamsters, are much smaller than humans and their respiratory tracts are also small. Their respirable particle size range is less than 500 nm with deposition efficiency increasing consistently down to a few tens of nm. The present device operates in this size range and is ideally suited for delivery of drugs to the deep lung of animal models. DNG generates a high concentration (>107 particles/ml) of fine particles, so it is easy to deposit drugs in microgram quantities in animals' lungs. This would enable meaningful efficacy and safety studies with a number of candidate drugs for inhalation therapy. In Phase I project, we demonstrated the feasibility of DNG concept based on high-frequency ultrasonic nebulization of drug solutions followed by diffusion drying. A prototype was built and extensively tested. It was used for preliminary animal exposure experiments that demonstrated for the first time the feasibility of delivering a chemopreventive agent difluoromethylornithine (DFMO) to A/J mice in adequate quantities by inhalation. Phase II project is aimed at building a turnkey version of DNG that would deliver drug particles reliably and in a repeatable manner. This device is planned to be used for studies on biodistribution of inhaled drugs (DFMO and docetaxel) in A/J mice as a function of particle size. Docetaxel will be studied because it is a chemotherapeutic agent that is a candidate for inhalation therapy of adenocarcinoma. Further, DNG will be used for delivering radioactive particles to A/J mice, in order to determine the penetration of the drug into the peripheral regions of the lung as a function of particle size. The DNG technology is also promising for delivery of fine mist to human lungs through a ventilator and for generation of fine dry powder for medical applications. This project is directly relevant to the treatment of the cancer of deep lung (adenocarcinoma) using inhalation therapy. It provides a drug nanoparticle generator that is essential to inhalation studies using small animals. The project plan includes deposition and biodistribution studies relevant to inhalation delivery of a chemopreventive and a chemotherapeutic drug, which would be followed by safety and efficacy studies in a future project and would pave the way to clinical trials for these inhalable drugs.

描述（由申请人提供）：计划在该项目中开发通用的交钥匙药物纳米颗粒发生器（DNG）。这种粒子发生器的立即应用是在动物模型中测试可吸入的新药物。大多数用于吸入疗法的动物模型，例如小鼠和仓鼠，都比人类小得多，呼吸道也小。它们可呼吸的粒径范围小于500 nm，沉积效率始终增加到几十nm。目前的设备在此尺寸范围内运行，非常适合向动物模型深肺输送药物。 DNG产生高浓度（> 107个颗粒/ml）的细颗粒，因此在动物的肺中以微克数量的数量沉积药物很容易。这将通过许多候选药物用于吸入疗法，从而实现有意义的功效和安全性研究。 在第一阶段项目中，我们证明了基于药物溶液的高频超声雾化，然后进行扩散干燥的DNG概念的可行性。建造并进行了广泛的测试。它用于初步的动物暴露实验，该实验首次证明了将化学预防剂差异甲基氨酸氨基氨酸（DFMO）提供给A/J小鼠的可行性。 II期项目旨在构建DNG的交钥匙版本，该版本将以可靠的方式可靠地提供药物颗粒。该设备计划用于研究A/J小鼠中吸入药物（DFMO和Docetaxel）生物分布的研究。将研究多西他赛，因为它是一种化学治疗剂，是腺癌吸入疗法的候选者。此外，DNG将用于向A/J小鼠传递放射性颗粒，以确定药物渗透到肺部的外围区域，这是粒径的函数。 DNG技术也有望通过呼吸机向人类肺部输送细雾，并为医疗应用生成细粉末。 该项目与使用吸入疗法治疗深肺（腺癌）的治疗直接相关。它提供了一种使用小动物吸入研究至关重要的药物纳米颗粒发生器。该项目计划包括与吸入化学预防和化学治疗药物的吸入递送有关的沉积和生物分布研究，随后将在未来的项目中进行安全性和效力研究，并将为这些不耐受药物的临床试验铺平道路。