(465a) High-Throughput Biomimetic Assay Designed to Quantify Antimalarial Efficacy Conference: AIChE Annual MeetingYear: 2015Proceeding: 2015 AIChE Annual MeetingGroup: Chemical Engineers in MedicineSession: Diagnostics, Treatments and Theranostics Time: Wednesday, November 11, 2015 - 8:30am-8:51am Authors: Ketchum, M., Rimer, J. D., University of Houston Vekilov, P. G., University of Houston High-throughput Biomimetic Assay Designed to Quantify Antimalarial Efficacy Megan A. Ketchum, Jeffrey D. Rimer, Peter G. Vekilov Department of Chemical and Biomolecular Engineering, University of Houston, 4800 Calhoun Rd., Houston, TX 77204 Crystallization is associated with the pathogenesis of several pathological and infectious diseases in humans. In malaria, parasites utilize crystallization to prevent eradication by sequestering toxic hematin (released by the catabolization of hemoglobin) into innocuous crystals termed hemozoin. The sequestration of hematin into hemozoin is the target of numerous antimalarial drugs that inhibit crystallization, thereby increasing hematin supersaturation and eliminating the parasite from the body due to the cytotoxicity of hematin.1 Parasite resistance to current antimalarials is spreading, fueling the demand for the development of new antimalarial drugs. Assays play an integral role in the discovery of new pharmaceutical drugs for diseases. High throughput assays are used by companies to test large libraries of drugs containing thousands of compounds to identify lead candidates. Here, we discuss a new method to screen for effective growth inhibitors of hematin crystallization. A relevant assay must mimic the parasite digestive vacuole (DV), which is a complex environment that is comprised of membrane interfaces, an acidic aqueous solution with pH 4.8 − 5.5, and lipids. While there is still debate regarding the medium (aqueous or organic) from which soluble hematin reaches the crystals and associates to them, we have provided convincing evidence that the lipid environment is crucial for crystal growth.2, 3 To this end, we use a two-phase system of citric buffer saturated octanol (CBSO) to emulate physiological conditions in the DV. We designed an assay for quantifying hematin crystallization in the presence of putative growth modifiers to screen molecules as potential antimalarial drugs. This assay successfully determines IC50 values of common drug compounds, proving the usefulness of the assay for testing of new drugs. The use of biomimetic solutions also provides a method of analyzing the fundamental mechanism(s) of drug-crystal interactions, which may prove to be an integral component of drug design that is capable of circumventing combinatorial approaches used to select and screen potential drugs. References 1. Olafson, K.N., M.A. Ketchum, J.D. Rimer, and P.G. Vekilov, Mechanisms of Hematin Crystallization and Inhibition by the Antimalarial Drug Chloroquine. Proceedings of the National Academy of Sciences U S A, 2015. 112: p. 4946-4951. 2. Ketchum, M.A., K.N. Olafson, E.V. Petrova, J.D. Rimer, and P.G. Vekilov, Hematin crystallization from aqueous and organic solvents. Journal of Chemical Physics, 2013. 139(12). 3. Olafson, K.N., J.D. Rimer, and P.G. Vekilov, Growth of Large Hematin Crystals in Biomimetic Solutions. Crystal Growth & Design, 2014. 14(5): p. 2123-2127.