Painless electroporation with a new needle-free microelectrode array to enhance transdermal drug delivery

A microelectrode array was designed to minimize the pain sensation of electroporation for enhancing transdermal drug delivery. The influence of the size of the electrode-skin contact area and of the distance between electrodes on the pain sensation was tested on human volunteers. The pain level decreased with the dimension of electrode-skin contact area and with inter-electrode distance. When both reached about 0.5 mm, the pain level was not perceptible even at the threshold of transdermal electroporation level of sixty electric pulses at 150 V, 1 ms at 1-10 Hz. An array of 11 x 11 alternately connected electrodes with 0.6 x 0.6 mm dimension was fabricated. The electric thresholds for effective drug delivery, using toluidine blue O as a marker on mouse skin, was found to be the same for microelectrode arrays as for larger electrodes and wider inter-electrode distances. In vivo transdermal electroporation using microelectrode array with 180 pulses of 150 V, 0.2 ms at 1 Hz, followed by 30 min methotrexate (MTX) occlusion increased more than 4 fold the systemic MTX level in mice. The results demonstrated the potential of painless delivery of significant amounts of chemotherapeutic agents through skin with the new electrode arrays in a clinical setting.