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 electrotransfer in vivo for gene therapy, as well as for drug delivery. In both cases, it is essential to know the electric field distribution in the tissues: the targeted tissue must be submitted to electric field intensities above the reversible permeabilisation threshold (to actually permeabilise it) and below the irreversible permeabilisation threshold (to avoid toxic effects of the electric pulses). A three-dimensional finite element model was built. Needle electrodes of different diameters were modelled by applying appropriate boundary conditions in corresponding grid points of the model. The observations resulting from the numerical calculations, like the electric field distribution dependence on the diameter of the electrodes, were confirmed in appropriate experiments in rabbit liver tissue. The agreement between numerical predictions and experimental observations validated our model. Then 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 rabbit liver tissue in vivo. Therefore the maximum of induced transmembrane potential difference in a single cell of the rabbit liver tissue can be estimated to be 394+/-75 and 694+/-136 mV, respectively, for reversible and irreversible electroporation threshold. These results carry important practical implications.
Miklavcic
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University of Ljubljana, Faculty of Electrical Engineering, Slovenia.
Semrov
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Mekid
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Mir
L M
LM
D000818:Animals; D002463:Cell Membrane Permeability; D004247:DNA / Q000008:administration & dosage*; D004558:Electric Stimulation / Q000379:methods; D018274:Electroporation / Q000379:methods*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D008962:Models, Theoretical; D011817:Rabbits; D015203:Reproducibility of Results
D004247:DNA