A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy

Permeabilising electric pulses can be advantageously used for DNA electrotr ansfer in vivo for gene therapy, as well as for drug delivery. In both case s, it is essential to know the electric field distribution in the tissues: the targeted tissue must be submitted to electric field intensities above t he reversible permeabilisation threshold (to actually permeabilise it) and below the irreversible permeabilisation threshold (to avoid toxic effects o f the electric pulses). A three-dimensional finite element model was built. Needle electrodes of different diameters were modelled by applying appropr iate boundary conditions in corresponding grid points of the model. The obs ervations resulting from the numerical calculations, like the electric fiel d distribution dependence on the diameter of the electrodes, were confirmed in appropriate experiments in rabbit river tissue. The agreement between n umerical predictions and experimental observations validated our model. The n it was possible to make the first precise determination of the magnitude of the electric field intensity for reversible (362+/-21 V/cm, mean +/- S.D .) and for irreversible (637 +/- 43 V/cm) permeabilisation thresholds of ra bbit liver tissue in vivo. Therefore the maximum of induced transmembrane p otential difference in a single cell of the rabbit liver tissue can be esti mated to be 394 +/- 75 and 694 +/- 136 mV, respectively, for reversible and irreversible electroporation threshold. These results carry important prac tical implications. (C) 2000 Elsevier Science B.V. All rights reserved.