Microhydrogel Depot for Sustained Delivery of Prophylactic Bioscavenger

Neurotoxic organophosphorus (OP) agents (e.g. sarin, soman, VX and tabun) were developed initially as pesticides and adapted for chemical warfare. OP agents are fast acting and lethal at even very low doses. Countering the threat of intoxication by OP nerve agents is an important mission for homeland security. Currently, the most promising strategy to counter OP intoxication is to scavenge the agents using injectable butyrylcholinesterase. BuChE has low substrate specificity and thus may offer a broad spectrum protection against OP agents by irreversible binding to the toxins. Human plasma-derived BuChE is effective but it is difficult to produce large quantities. Recombinant BuChE lack the necessary stability and extended circulation over sufficient periods to provide adequate prophylaxis while minimizing the need for repeated administration. Luna proposes to develop a microhydrogel-based physiological depot for long-term delivery of recombinant BuChE at proper release rates. The intramuscularly injectable depot will be able to maintain BuChE plasma concentration that is effective to bioscavenger OP agents for multiple weeks. Phase I will demonstrate the technical feasibility using in vitro assays assisted by computational modeling and Phase II will demonstrate the depot performance in appropriate animal models in preparation of IND filing.