Data Sheet 1_Boolean network and meshless simulations for the comparison of transport and reaction mechanisms arising in one-short tri-exponential and uniform infusion electrochemotherapeutic treatments.pdf

Drug administration via the bloodstream involves some transport and reaction mechanisms (RTMs), such as extravasation, perfusion along blood vessels, transmembrane and interstitial transport, protein dissociation and association, and lymphatic drainage. These RTMs can be influenced by the type of pharmacokinetic (PK) profile used for drug delivery in the circulatory system, as well as by the bloodstream velocity λinl. In electroporated tissues, the electric field magnitude (E) can also affect the RTMs because it brings about vessel vasoconstriction, cell membrane and vessel wall electro-permeabilization, and changes in tissue porosity. In the present work, in-house computational tools are employed to examine how the combination of E and λinl influences the RTM′s existence, interaction, and rates arising in electrochemotherapy for two different PKs: One-short tri-exponential (TPK), where the drug concentration decreases exponentially after a one-short infusion, and one uniform (UPK), where the drug concentration is kept constant during the whole treatment. First, the ratios between extracellular, free intracellular, and bound intracellular concentrations are obtained from numerical simulations with a meshless code previously developed, calibrated, and validated. Subsequently, the interaction between the RTMs is investigated by means of a Boolean model presented here that is based on the comparison of the spatio-temporal evolution of the concentration ratios. Several combinations of E (0 kV/m; 46 kV/m; 70 kV/m), λinl (1×10−4m/s; 1×10−3m/s; 1×10−2m/s), and PK (TPK and UPK) are tested. The in silico findings indicate that RTM′s existence, interaction, and rates can vary between the two PKs (TPK and UPK) for a specific permutation of E and λinl. Nevertheless, common features are identified between these pharmacokinetic profiles. In general, the lower E, the more uniform the transmembrane transport in the radial and axial direction; the decrease of λinl also improves the radial homogeneity of this transport mechanism but negatively influences the axial uniformity. The uniformity of the mechanisms of association and dissociation is only altered monotonously by E (Vélez Salazar and Patiño Arcila, 2025).