**4. Electroporation mechanisms**

The development of theoretical models has developed our understanding of electroporation mechanism. Electropermeabilization of cells mainly involves the interaction of the electric field with the lipid domains of the cell membrane. Experimentally measured quantities consist of the membrane lifetimes, the current, the membrane conductance and transmembrane voltage. Regarding to the accumulated evidence, the pores are formed because of the electric field. The transient aqueous pore theory describes the main features of electropermeabilization, which is one major consequence of electroporation. Molecular transport of charged molecules appears to be predominantly due to electrical flow through pores, such that the elevated transmembrane voltage plays two roles: (a) creation of pores and (b) provision of a local driving force [Weaver and Chizmadzhev, 1996]. Electrochemotherapy (ECT) is a cancer therapy that conjugates the administration of a chemotherapy agent to the delivery of permeabilizing pulses released singularly or as bursts. This approach results in higher number of anticancer mole‐ cules delivered to their biological targets, but is also associated to undesirable side effects such as pain and muscular spasms. A new electroporator delivering eight biphasic pulses at the voltage of 1,300 V/cm lasting + 50 μsec each, with a frequency of 1 Hz, and with 10-μsec interpulse intervals (total treatment time: 870 μsec/cm<sup>2</sup> of treated area) was tested on the human lung cancer cell line (A549) and both in mice xenografts and rabbits with spontaneous tumors. The tumor cell line treated with electroporation showed efficient drug delivery suggesting further cell death. In addition, *in vivo* data demonstrated that the new permeabi‐ lizing protocol adopting biphasic electric pulses displays a significant higher efficacy com‐ pared to previous ECT treatments and consequently, substantial reduction of the morbidity [Spugnini et al., 2014].
