Developing Human-Compatible Needleless Delivery Systems for Administering Bioscavengers

The goals of this proposal are: 1) to identify a BChE formulation that will deliver the target systemic dose via the lungs; 2) to ensure that the integrity of the BChE protein is unaffected by the aerosolization process; and 3) to measure the efficiency ofdelivering BChE to the systemic circulation via inhalation using the AERx System. BChE is a drug candidate for detoxification of chemical warfare agents, including organophosphorus (OP). BChE has been shown to function as a biological scavenger toprotect against the pharmacological and behavioral toxicity of OP poisons. The lung represents an attractive route for drug delivery to the systemic circulation due to its large surface area and intimate contact with the blood. The AERx System is a novelaerosol generating system that converts, at a pre-programmed moment during inspiration, a unit dose of liquid formulation into a fine aerosol in about 1 second, which is then drawn into the lungs using the patient?s inhalation air flow. In clinicaltrials, the AERx System has successfully delivered a variety of molecules, including insulin and morphine to the systemic circulation, and has the potential to deliver a wide range of other drugs and biologics. The current global environment mandates thatthe United States military be able to resist asymmetric warfare, including biological and chemical threats. The proposed project addresses the threat posed by organophosphorus nerve agents that could be used in chemical warfare. Specifically, thisproject aims to establish the feasibility of using the AERx Pulmonary Delivery System to deliver butyrylcholinesterase (BChE) via inhalation, which would provide convenient, non-invasive protection against nerve-agents. This approach could lead tocommercialization of the AERx drug-device combination to deliver BChE and perhaps other bioscavengers by the military. Other commercial opportunities include treatment for cocaine intoxication and pesticide overdose for civilian populations. Furthermore,AERx technology has broad applications for a wide range of molecules and will likely be used to deliver emerging biopharmaceuticals derived from the genomic revolution. With the market for inhaled and intranasal drugs projected to reach $36 billion by2005 at a 25% growth rate (Drug Delivery, Vol 3: The Market for Pulmonary Drug Delivery Systems)Aradigm is uniquely positioned to offer a non-invasive approach to delivering a wide variety of compounds.