Nanoparticle Generator for Animal Inhalation Experiments

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.