This project will provide a significantly improved method for intra-pulmonary drug delivery in pediatric patients who are intubated or have a tracheostomy. Currently available aerosolizing devices are limited in that only certain agents and only a small fraction (less than a few percent) of such drugs are actually delivered to the distal lung zones. We propose a novel Intra-Pulmonary Aerosol Generator (IPAG), which would be a 1 or 2 mm diameter tube inserted within the endotracheal tube. This IPAG will be capable of generating micro- aerosols that would reach the remote airways and alveoli with an efficiency approaching 100%. Further, our device is unique in that it uses extremely low airflow to generate respirable aerosols to minimize any potential barotrauma. Moreover, this aerosolizer can be synchronized to the inspiratory phase of the ventilator cycle without the introduction of significant resistance within the flow circuit. A broad range of ventilated pediatric patients fro a variety of etiologies including pneumonia, acute lung injury and acute respiratory distress syndrome would benefit from our proposed aerosol generator. IPAG would enable delivery of agents such as, antibiotics (for treatment of pneumonia and sepsis), as well as glucose, steroids, analgesics, and sedatives. IPAG allows for a simple means of essential drug delivery during resuscitation of patients and bypasses the immediate need for intravenous access. This is of particular utility in neonatal resuscitation and during transport of such infants from rural centers where intravenous access can be challenging and difficult. The core technology for the proposed device has been developed by Powerscope and is being used in preclinical work involving aerosol generation in vitrectomized gas-filled porcine eyes for inhibition of scar tissue growth caused by retinal detachment. We propose to translate and develop this technology into a feasible product that can be synchronized to ventilation and complement airflow dynamics. Aerosol generation and particle size distribution will be characterized with in-vitro models. Neonatal lamb model will be used to quantify pulmonary distribution, and systemic bio-absorption of aerosolized antibiotics delivered with IPAG. Completion of this Phase I SBIR project would prepare the grounds for efficacy studies with animal models of pneumonia and acute lung injury in the Phase II project with further safety studies in order to prepare the devic for future clinical trials.
This project is relevant to public health because it addresses an important need of hundreds of thousands of pediatric patients that are intubated each year and require medications, such as antibiotics, steroids, etc., which could best be delivered directly to the lungs, but are often given systemically due to the lack of an effective pulmonary delivery method. To address this need of intubated patients, we propose Intra-Pulmonary Aerosol Generator (IPAG), which generates aerosols at the tip of a catheter included in the endotracheal tube, thus combining the benefits of (i) aerosolization, which ensures effective penetration of the drugs in the lungs, and (ii) drug release within the respiratory tract to ensure nearly 100% delivery efficiency, as opposed to just a few percent delivery with extra-pulmonary aerosol generation.