In vitro polymer based models of tumors under electric fields: comparison with in silico simulations and in vivo measurements

G MARSHALL; N. OLAIZ; E MOCSKOS; L. COLOMBO; C. SUAREZ; G. GONZÁLEZ; M. RISK; A SOBA,; L. NUÑEZ; J. C. CALVO; F. V. MOLINA

Salerno, Italia

Congreso; Symposium: Polymers for Biomedical and Pharmaceutical, in Proc. of the Polymer Processing Society 24th Annual Meeting, PPS-24; 2008

Polymer Processing Society

In this study, tumor tissues are simulated in vitro with natural polymer gels (collagen type-I and agar-agar) to elucidate electrochemical processes taking place during electric current-based therapies. Use of electric currents in chemotherapy greatly improves drug transport and delivery of charged therapeutic agents synergistically with diffusion and convection. Electric current-based cancer treatment consist in the passage of an electric current, whether direct (electrochemical treatment, EChT) or micro-pulsed (electrochemotherapy, ECT), through two or more electrodesinserted locally in the tumor tissue. Extreme pH changes at tissue level with significant water   motion (EChT) or the creation of transient membrane porous at the cell level that facilitates transmembrane penetration of cytotoxic agents into the cell (ECT), are main electrochemical effects. Here we explore a combination of ECT and EChT with drugloaded charged nanoparticles (dendrimers) with the final goal of enhancing drug transport and delivery to tumor tissues and cells. Polymer in vitro measurements are contrasted with in silico simulations (using a mathematical model based on the Nernst-Planck, Poisson and Navier-Stokes equations for ion transport, electric field distribution and fluid flow, respectively) and with in vivo measurements using BALB/c mice bearing subcutaneous tumors. Preliminary results suggest that the use of nanoparticle-charged drug delivery systems and tuned electric fields can significantly increasedrug transport and delivery.