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.
Wong
Tak-Wah
TW
Department of Dermatology, Biochemistry and Molecular Biology & Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. twwong@mail.ncku.edu.tw <twwong@mail.ncku.edu.tw>
Chen
Ching-Hung
CH
Huang
Chien-Chun
CC
Lin
Cheng-De
CD
Hui
Sek-Wen
SW
D000279:Administration, Cutaneous; D000818:Animals; D018274:Electroporation / Q000295:instrumentation* / Q000379:methods; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008839:Microelectrodes; D009339:Needles; D010147:Pain Measurement / Q000379:methods; D012869:Skin Absorption / Q000502:physiology*