Influence of electroporation parameters on the reaction and transport mechanisms in electro-chemotherapeutic treatments using Boolean modeling and the Method of Fundamental Solutions.

The systemic administration of chemotherapeutic drugs involves some reaction and transport mechanisms (RTMs), including perfusion along the blood vessels, extravasation, lymphatic drainage, interstitial and transmembrane transport, and protein association and dissociation, among others. When tissue is subjected to the controlled application of electric pulses (electroporation), the vessel wall and cell membrane are permeabilized, capillaries are vasoconstricted and tissue porosity is modified, affecting the RTMs during electro-chemotherapeutic treatments. This study is a theoretical investigation about the influence of the electric field magnitude (E), number of electroporation treatments (N) and duration of each electroporation protocol (T) on the presence, interaction and rates of the RTMs using in-house computational tools.

In silico study about the influence of electroporation parameters on the cellular internalization, spatial uniformity, and cytotoxic effects of chemotherapeutic drugs using the Method of Fundamental Solutions.

Reversible electroporation is a suitable technique to aid the internalization of medicaments in cancer tissues without inducing permanent cellular damage, allowing the enhancement of cytotoxic effects without incurring in electric-driven necrotic or apoptotic processes by the presence of non-reversible aqueous pores. An adequate selection of electroporation parameters acquires relevance to reach these goals and avoid opposite effects. This work applies the Method of Fundamental Solutions (MFS) for drug transport simulations in electroporated cancer tissues, using a continuum tumor cord approach and considering both electro-permeabilization and vasoconstriction effects.

Influence of electric pulse characteristics on the cellular internalization of chemotherapeutic drugs and cell survival fraction in electroporated and vasoconstricted cancer tissues using boundary element techniques.

Electroporation has emerged as a suitable technique to induce the pore formation in the cell membrane of cancer tissues, facilitating the cellular internalization of chemotherapeutic drugs. An adequate selection of the electric pulse characteristics is crucial to guarantee the efficiency of this technique, minimizing the adverse effects. In the present work, the dual reciprocity boundary element method (DR-BEM) is applied for the simulation of drug transport in the extracellular and intracellular space of cancer tissues subjected to the application of controlled electric pulses, using a continuum tumour cord approach, and considering both the electro-permeabilization and vasoconstriction phenomena.

Influence of electric field, blood velocity, and pharmacokinetics on electrochemotherapy efficiency.

The convective delivery of chemotherapeutic drugs in cancerous tissues is directly proportional to the blood perfusion rate, which in turns can be transiently reduced by the application of high-voltage and short-duration electric pulses due to vessel vasoconstriction. However, electric pulses can also increase vessel wall and cell membrane permeabilities, boosting the extravasation and cell internalization of drug. These opposite effects, as well as possible adverse impacts on the viability of tissues and endothelial cells, suggest the importance of conducting in silico studies about the influence of physical parameters involved in electric-mediated drug transport.