Seminar Detail

Abstract: Antiretroviral (ARV) drugs have been significantly successful in treating HIV infected patients throughout the past decade. Recent studies, however, have shown that ARVs distribute heterogeneously in tissues such as the lymph nodes (LNs), therefore not penetrating sufficiently to suppress the virus. In the Zurakowski lab we have previously developed a mathematical model that solves pharmacokinetic (PK) reaction and spatial diffusion dynamics on a fully reconstructed 3D geometry of a murine LN. The simulation outputs of the model reproduce the spatial patterns of ARV distributions that have been formerly observed in LNs using direct imaging techniques. The transport mechanisms into the LN are considered to be diffusion-like and via blood or fluid lymph only, either as free drug or as intercellular cargo via the T-cells. In this project, a local sensitivity analysis was performed on the existing protease inhibitor (PI) drugs class from the ARVs to determine the effects and sensitivities of different drug transport mechanisms into the LN. Preliminary analyses show that the transport rates of drugs leaving the LN are more sensitive in the case of free drugs vs. intracellular transport, and the transport rates of drugs entering the LN are more sensitive in the case of intracellular transport. This method can provide a valuable tool for designing more penetrable ARVs and contribute to a better drug delivery design.

Bio: Yasmin majored in physics as an undergraduate student in Iran. She got her first master’s degree in condensed mattered physics. She worked on mathematical models of cancer for her thesis. She studied molecular biophysics at Johns Hopkins for her second master’s degree, where she worked on protein-protein interactions. She is currently co-advised by Dr. Ryan Zurakowski and Dr. Jason Gleghorn from the Biomedical Engineering department, working on mathematical models and drug design.