Wong Tak-Wah, Chen Ching-Hung, Huang Chien-Chun, Lin Cheng-De, Hui Sek-Wen
Department of Dermatology, Biochemistry and Molecular Biology & Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
J Control Release. 2006 Feb 21;110(3):557-65. doi: 10.1016/j.jconrel.2005.11.003. Epub 2005 Dec 13.
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.
设计了一种微电极阵列，以尽量减少电穿孔引起的疼痛感，从而增强经皮给药效果。在人类志愿者身上测试了电极与皮肤接触面积的大小以及电极之间的距离对疼痛感的影响。疼痛程度随着电极与皮肤接触面积的大小以及电极间距的增加而降低。当两者都达到约0.5毫米时，即使在150伏、1毫秒、1 - 10赫兹的经皮电穿孔水平阈值为60个电脉冲时，疼痛程度也无法察觉。制作了一个由11×11个交替连接的电极组成的阵列，电极尺寸为0.6×0.6毫米。以甲苯胺蓝O作为小鼠皮肤标记物，发现微电极阵列有效给药的电阈值与较大电极及更宽电极间距时相同。在小鼠体内，使用微电极阵列进行经皮电穿孔，施加180个150伏、0.2毫秒、1赫兹的脉冲，随后封闭甲氨蝶呤（MTX）30分钟，使小鼠体内MTX的全身水平提高了4倍多。结果表明，在临床环境中，使用新型电极阵列可通过皮肤无痛输送大量化疗药物。
