Blood Brain Barrier Drug Delivery of Therapeutics for Chemical Warfare Agents

Technical Abstract Impel NeuroPharma has developed a novel non-invasive delivery system, the POD device that targets drug to the upper third of the nasal cavity which results in direct and rapid transport of drug to the CNS via the olfactory perineural pathways, effectively bypassing the BBB. In Phase I of this research contract Impel successfully characterized and tested both an aqueous and a dry powder form of 2-PAM for administration via Impel"s POD device, which led to dramatic increases in 2-PAM brain concentrations and lower plasma concentrations compared to IV administration. In Phase 2 of this research contract, Impel will conduct critical studies in order to ready this product for clinical trials and ultimately for use in the battlefield setting as an effective treatment for nerve gas exposure. Impel"s four main objectives are 1) Determine doses of POD administered 2-PAM and MMB-4 with optimal CNS exposure in rats; 2) Demonstrate the CNS protective effects of POD administered 2-PAM and MMB-4 in rats exposed to the nerve agents sarin and soman; 3) Develop optimized POD device for battlefield oxime use; and 4) Determine tolerability and drug distribution of POD administered oxime in non-human primates.