Sim Biology- Driven PK–PD Modeling of Exosome (miR-378) Delivery to Reduce Collagen Overproduction in Cardiac Fibrosis

Abstract

Arnav Guduri

Cardiac Fibrosis lacks consistent and reliable treatment utilizing drugs such as ACE inhibitors, coagulants, and ARBS. As modeling and simulation are increasingly used in drug development to understand pharmacokinetic-pharmacodynamic (PK-PD) relationships and support preclinical research, I simulate an extracellular vesicle (EV), an exosome modified with miR378, to reduce collagen buildup that causes Cardiac Fibrosis (CF) in the cardiac interstitium. Using the Simbiology® graphical user interface (GUI), I perform a bolus dose, a pulsed dose, and a binding + maintenance dose. I demonstrated presentational pathway figures, parameters, species estimation, and thermodynamic binding affinities. The results show that bolus and multiple-pulse doses are highly effective at stopping fibrotic collagen production in the interstitial space.

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