Kigasawa Kaoru, Kajimoto Kazuaki, Watanabe Misuzu, Kanamura Kiyoshi, Saito Akiyoshi, Kogure Kentaro
Graduate School of Life Science, Hokkaido University, Japan.
Biol Pharm Bull. 2009 Apr;32(4):684-7. doi: 10.1248/bpb.32.684.
A novel iontophoretic system utilizing ion-exchange membranes is effective for selective transdermal delivery of ionized drugs. In the present study, we examined in vivo availability and safety of ion-exchange iontophoresis in the transdermal delivery of anionic diclofenac, a well known anti-inflammatory medication, to rat dorsal skin. While iontophoresis increased the plasma concentration of diclofenac sodium and skin injury was not observed, no anti-inflammatory effect was exerted. To enhance the efficiency of transdermal delivery of diclofenac sodium, iontophoresis was combined with topical application of one of three terpenes (menthol, nerolidol or geraniol) as chemical enhancers. By combining iontophoresis with geraniol, the plasma concentration of diclofenac sodium increased over 20-fold, and suppression of inflammation was achieved. Skin irritation was not seen even after 1.5 h iontophoresis. The enhancing effect of geraniol is attributed to increased penetration of the drug into the stratum corneum as well as enhanced transport across the anion-exchange membrane. Ion-exchange iontophoresis combined with geraniol is a highly effective transdermal delivery system.
一种利用离子交换膜的新型离子电渗系统对于离子化药物的选择性经皮递送是有效的。在本研究中，我们考察了离子交换离子电渗法在将阴离子型双氯芬酸（一种知名的抗炎药物）经皮递送至大鼠背部皮肤中的体内有效性和安全性。虽然离子电渗法提高了双氯芬酸钠的血浆浓度且未观察到皮肤损伤，但未发挥抗炎作用。为提高双氯芬酸钠的经皮递送效率，离子电渗法与三种萜类化合物（薄荷醇、橙花叔醇或香叶醇）之一作为化学促进剂的局部应用相结合。通过将离子电渗法与香叶醇相结合，双氯芬酸钠的血浆浓度增加了20多倍，并实现了炎症抑制。即使在1.5小时的离子电渗后也未观察到皮肤刺激。香叶醇的增强作用归因于药物进入角质层的渗透率增加以及跨阴离子交换膜的转运增强。离子交换离子电渗法与香叶醇相结合是一种高效的经皮递送系统。
