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: 7824735
• 负责人: AMIR A NAQWI
• 金额: $ 1.63万
• 依托单位: POWERSCOPE, INC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2009-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7824735
• 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; Development; Devices; Diffusion; Dose; Drops; Drug Delivery Systems; Drug Evaluation; Electronics; Excision; FDA approved; Film; Frequencies; Future; Generations; Hamsters; Human; Inhalation Therapy; Learning; Liquid substance; Lung; Lung Adenocarcinoma; Medical; Modeling; Mus; Nebulizer; Non-Small-Cell Lung Carcinoma; Particle Size; Penetration; Peripheral; Pharmaceutical Preparations; Phase; Powder dose form; Production; Radioactive; Respiratory System; Respiratory tract structure; Safety; Scientist; Solutions; Source; Squamous cell carcinoma; Supportive care; Surface; Technology; Testing; Time; Transducers; Ultrasonic Transducer; Ultrasonics; Ventilator; Water; Work; aqueous; base; cancer therapy; chemotherapeutic agent; commercialization; density; docetaxel; drug inhalation; falls; interest; meetings; nano; nanoparticle; particle; prevent; prototype; research study; response; safety study; 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）：本项目计划开发通用交钥匙药物纳米颗粒发生器（DNG）。这种粒子发生器的一个直接应用是在动物模型中测试新的吸入药物。大多数吸入疗法的动物模型，如小鼠和仓鼠，比人类小得多，它们的呼吸道也很小。它们的可呼吸颗粒尺寸范围小于 500 nm，沉积效率持续增加至几十 nm。本装置在此尺寸范围内工作，非常适合将药物输送到动物模型的深肺。 DNG产生高浓度（>107颗粒/ml）的细颗粒，因此很容易在动物肺部沉积微克量的药物。这将使一些吸入疗法候选药物的有意义的功效和安全性研究成为可能。 在第一阶段项目中，我们论证了基于药物溶液高频超声雾化随后扩散干燥的DNG概念的可行性。原型已经构建并进行了广泛的测试。它用于初步动物暴露实验，首次证明了通过吸入向 A/J 小鼠提供足量化学预防剂二氟甲基鸟氨酸 (DFMO) 的可行性。第二阶段项目旨在构建交钥匙版本的 DNG，以可重复的方式可靠地输送药物颗粒。该装置计划用于研究吸入药物（DFMO 和多西紫杉醇）在 A/J 小鼠体内的生物分布与粒径的函数关系。多西紫杉醇将被研究，因为它是一种化疗药物，是腺癌吸入治疗的候选药物。此外，DNG 将用于向 A/J 小鼠递送放射性颗粒，以确定药物渗透到肺部周围区域的情况，作为颗粒大小的函数。 DNG 技术还有望通过呼吸机向人体肺部输送细雾，并生成用于医疗应用的细干粉。 该项目与使用吸入疗法治疗深部肺癌（腺癌）直接相关。它提供了一种药物纳米粒子发生器，这对于使用小动物进行吸入研究至关重要。该项目计划包括与化学预防药物和化疗药物的吸入给药相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有效性研究，并为这些吸入药物的临床试验铺平道路。