Transdermal Delivery of Hyaluronan Tetrasaccharide by Constant Current Iontophoresis

Madoka Kage, Y. Tokudome
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Abstract

It is well known that scars, wrinkles, and intra articular diseases such as rheumatoid arthritis can be healed by injecting hyaluronan (HA) into the skin and joints. However, based on its varying molecular size, skin penetration of HA may be limited. In this study, we aimed to investigate the effect of transdermal enhancements such as electroporation (EP) and iontophoresis (IP) on the in vitro skin permeability of HA tetrasaccharide (HA4) to deliver HA4 into skin effectively. The effects of EP and IP on the skin permeation of HA4 were studied in in vitro skin permeation experiments. Cumulative amounts of HA4 through full-thickness skin after 6 h were 0.3 μg/cm2 for passive diffusion, 2.3 μg/cm2 after application of EP (100 V, 10 ms, 50 times), 2310.7 μg/cm2 after application of IP (cathodal IP, 0.1 mA/cm2), and 797.9 μg/cm2 after application of IP (cathodal IP, 0.05 mA/cm2), respectively. The skin permeability of the IP (cathodal IP, 0.1 mA/cm2) treatment was about 7700 and 1000-fold increased than that of passive diffusion and the EP treatment. The cumulative amount of HA4 through stripped skin after 6 h was 1384.3 μg/cm2 for passive diffusion. The skin permeability of the cathodal IP (full-thickness skin, 0.05 mA/cm2) treatment was about 1.7-fold increased than that of passive diffusion (stripped skin). We showed that cathodal IP is useful for delivering HA4 into skin effectively.
恒电流离子电泳法透皮递送透明质酸四糖
众所周知,在皮肤和关节中注射透明质酸(HA)可以治愈疤痕、皱纹和类风湿关节炎等关节内疾病。然而,基于其不同的分子大小,透明质酸的皮肤渗透可能受到限制。在这项研究中,我们旨在研究透皮增强如电穿孔(EP)和离子透入(IP)对HA四糖(HA4)的体外皮肤通透性的影响,以有效地将HA4输送到皮肤中。通过体外皮肤渗透实验,研究了EP和IP对HA4皮肤渗透的影响。6 h后HA4通过全层皮肤的累积量为被动扩散0.3 μg/cm2, EP (100 V, 10 ms, 50次)作用后为2.3 μg/cm2, IP(阴极IP, 0.1 mA/cm2)作用后为2310.7 μg/cm2, IP(阴极IP, 0.05 mA/cm2)作用后为797.9 μg/cm2。电激电位(阴极电激电位,0.1 mA/cm2)处理的皮肤通透性分别是被动扩散和电位处理的7700倍和1000倍。经剥皮6 h后HA4的被动扩散累积量为1384.3 μg/cm2。阴极激电(全层皮,0.05 mA/cm2)处理的皮肤通透性比被动扩散(剥皮)处理的皮肤通透性提高约1.7倍。我们发现阴极IP可以有效地将HA4输送到皮肤中。
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