Intra-pulmonary aerosol delivery for intubated pediatric patients

描述（由申请人提供）：本项目将为气管插管或气管切开术的儿科患者提供一种显著改进的肺内给药方法。目前可用的雾化装置是有限的，因为只有某些药物，只有一小部分（不到百分之几）这样的药物被实际输送到远端肺区。我们提出了一种新型的肺内气溶胶发生器（IPAG），它将是一个直径1或2毫米的管子插入气管内管。这种IPAG将能够产生微气溶胶，以接近100%的效率到达远程气道和肺泡。此外，我们的设备的独特之处在于，它使用极低的气流来产生可吸入的气溶胶，以尽量减少任何潜在的气压损伤。此外，这种雾化器可以同步到呼吸机循环的吸气阶段，而不会在流动回路中引入显著的阻力。各种病因（包括肺炎、急性肺损伤和急性呼吸窘迫综合征）的广泛儿科通气患者将受益于我们提出的气溶胶发生器。IPAG将使诸如抗生素（用于治疗肺炎和败血症）、葡萄糖、类固醇、镇痛药和镇静剂等药物的输送成为可能。IPAG允许在患者复苏期间提供一种简单的基本药物输送方法，并绕过了静脉注射的迫切需要。这在新生儿复苏和从静脉注射可能具有挑战性和困难的农村中心运送这类婴儿时特别有用。该装置的核心技术已由Powerscope公司开发，并已用于临床前工作，包括在玻璃体切割的充满气体的猪眼中产生气溶胶，以抑制疤痕组织

DESCRIPTION (provided by applicant): 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.