Topical and Transdermal Iontophoretic Delivery of Methotrexate in Healthy and Psoriatic Human Skin

Abstract

Psoriasis is a condition of the skin which involves scales, dry patches, and inflammation. Methotrexate (logP: -0.236, MW: 454.44 g/mol) is administered orally or intravenously to treat psoriasis. The first pass metabolism and systemic side effects associated can be avoided by transdermal delivery. We investigated the iontophoretic delivery of methotrexate using healthy and psoriatic human skin to understand the effect of skin�s disease condition on topical and transdermal delivery. In vitro permeation testing using vertical Franz diffusion cell were conducted. Cathodal iontophoresis (0.5 mA/sq.cm for 4 h) delivered a significantly higher total amount of methotrexate into the skin and receptor when compared to that delivered by passive diffusion and anodal iontophoresis. A current density of 0.2 mA/sq.cm using cathodal iontophoresis and 10mg/mL donor concentration was optimized to obtain the target delivery through healthy human skin. There was no significant difference in receptor delivery for psoriatic skin as compared to healthy skin, while significantly higher methotrexate delivery in skin was observed for psoriatic skin as compared to healthy skin. Thus, cathodal iontophoresis delivered a significantly higher total amount of methotrexate as compared to passive diffusion and anodal iontophoresis. Significantly higher delivery in skin and hence significantly higher total delivery was observed for psoriatic skin as compared to healthy skin.