Enhanced delivery of 5-fluorouracil through shed snake skin by two new transdermal penetration enhancers

Abstract

The effectiveness of a new biodegradable penetration enhancer, dodecyl N, N-dimethylamino isopropionate (DDAIP) was compared to dodecyl N, N-dimethylamino acetate (DDAA), another biodegradable penetration enhancer, and to Azone®, lauryl alcohol (LA), and oleic acid (OA) in vitro using shed snake skin in modified Franz-type diffusion cells. 5-Fluorouracil (5FU), a hydrophilic drug with poor skin permeability, was used as a model permeant. Skin samples were pretreated with pure liquid enhancers. 5FU flux through the control and enhancer treated skin increased linearly with its concentration in the donor compartment. DDAIP and DDAA interacted with the skin rapidly (< 2 h), and the duration of action is at least 24 h. The transdermal flux of 5FU increased substantially (> 40-fold) with the dose of DDAIP up to 10 μ1. Thereafter the flux did not increase significantly. With DDAA no plateau effect was observed with the applied volumes up to 50 μ1. Skin pretreatment with 5 μ1 of DDAIP, DDAA, Azone®, LA, and OA increased the permeability of 5FU 69-, 24-, 23-, 5-, and 2-times, respectively. Substitution of a methyl group for a hydrogen atom in the acetate moiety of DDAA was observed to markedly increase transdermal penetration enhancement.