Transdermal Delivery of Hyaluronan Tetrasaccharide by Constant Current Iontophoresis

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.