Nanoparticle Generator for Animal Inhalation Experiments

描述（由申请人提供）：本项目计划开发一种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可吸入药物。大多数用于吸入治疗的动物模型，如小鼠和仓鼠，都比人类小得多，它们的呼吸道也很小。它们的可吸入颗粒尺寸范围小于500纳米，沉积效率持续增加到几十纳米。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产生的细颗粒浓度很高（bb0 ~ 107粒/ml），因此很容易在动物肺部以微克量级沉积药物。这将使一些吸入治疗候选药物的有效性和安全性研究成为可能。

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.