Localized for delivering drugs into cutaneous and sub-cutaneous

Localized chemotherapy and electroporation. With respect to surface tumors, a better local control of
the therapeutic agent may be simply realized by injection of the drug into the tumor42, 43, a procedure which is
facilitated by direct visualization. Nonetheless, in many cases the procedure does not necessarily ensure
accumulation of drugs into tumor cells, especially for very potent yet non-permeant drugs such as bleomycin44,
45. To alleviate this problem and improve the local distribution of chemotherapeutic agents, electroporation has
been proposed as an efficient method for delivering drugs into cutaneous and sub-cutaneous tumors 6-8, 12, 42-44,
. This method was developed into a clinical approach for skin cancer treatment adopted in many countries
around the world (it is available in Europe, and under initial approval in US). In some cases, this approach has
been met with unprecedented efficacy of ~94%56
. Electroporation (or electro-permeabilization) is a biophysical
phenomenon characterized by a sudden increase in the membrane permeability by several orders under exposure
Gamid Abatchev
Increasing Cancer Treatment Efficacy by Local Control of Drug Delivery and Simultaneous Radiotherapy
to strong external electric fields57, 58. The increased permeability is presumably a consequence of the occurrence
of transient nanopores (up to ~ 200 nm diameter) in the membrane due to the transmembrane voltage (Vm)
induced by Maxwell-Wagner polarization58
. The exponential dependency of the pore formation on voltage induces
a strong asymmetry with respect to membrane permeabilization owing to the rest potential59, 60
. Therefore, by
using bipolar electric pulses, the poration process may be more efficient since it is symmetrical with respect to the
orientation of the electric field. Consequently, a concomitant approach consisting of radiotherapy and electrochemotherapy
with bipolar electric pulses may present an improved clinical efficacy for treatment of superficial


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