Development of a long-acting, injectable controlled release butyrylcholinesterase formulation using predictive modeling.

Elevated levels of human butyrylcholinesterase (hBuChE) confer protection from chemical warfare nerve agents and other organophosphorous chemicals. As a prophylactic, the key to enabling this protection is the ability to maintain elevated concentrations of hBuChE in the plasma for days or weeks. Thus far, plasma-derived hBuChE and PEGylated recombinant forms of BuChE (rBuChE) have been tested in humans. However, both have fallen short of providing cost-effective protection in scenarios where repeated intravenous administration by a health care worker is impractical. Qrono proposes to meet the need for an organophosphorous prophylaxis with custom developed, injectable microparticles that will sustain hBuChE delivery for 10 days. In Phase I, Qrono optimized the design of hBuChE-containing microparticles using its proprietary formulation design software, validated their in vitro release and simulated their pharmacokinetics for animal models and humans. Qronos unique computational approach to formulation development provides greater efficiency and accuracy in the design of depot medications than the industry standard experiment driven methods. In Phases II and III, Qrono will test the pharmacokinetics and prophylactic capabilities of its hBuChE formulation with nerve agent challenge studies in animal models and then pursue commercialization through clinical trials.