The changes in the skin permeability barrier and epidermis of hairless mouse on oleic acid treatment

Background: The stratum corneum(SC) inhibits transepidermal water loss and makes a permeability barrier against foreign materials, so strategies to overcome relative impermeability of the SC is very important in transdermal drug delivery. This includes occlusion, hydration, chemical permeation enhancers, iontophoresis and sonophoresis. Oleic acid, which is one of the cis-unsaturated fatty acid and chemical permeation enhancers, increases the permeability of the lipophilic molecules and polar molecules through the SC. By spectrometry, calorimetry and the flux technique, the hypothesis that oleic acid does exist as a liquid within the SC lipids and enhances the transport of polar molecules across the SC by the formation of permeable interfacial defects within the SC lipid bilayers was suggested. Also, repeated application of oleic acid induces epidermal proliferation, hyperkeratosis and sebaceous gland hyperplasia; However the exact pathomechanism was not reported. Objective: We carried out some research to observe the mechanism by which oleic acid increases transdermal drug delivery and the effect to the skin permeability barrier and epidermis by repeated application. Methods: In the repeated treatment group, hairless mice(6 to 8 weeks) were treated with oleic acid once a day for 7 days unilaterally, and in the single treatment group, only one time. Transepidermal water loss(TEWL) was checked at 24hour after 1, 3 and 7 days of treatment and at 1 hour, 6 hours, 24 hours, 72 hours after single treatment. Biopsies were taken from treated and controlateral(control) sides immediately after the TEWL checks at each time for light microscopic(H and E stain) and electron microscopic studies. Results: In the repeated treatment group, TEWL was increased by day and epidermal proliferation and hyperkeratosis were also increased. In the single treatment group, TEWL was highly increased in the treated site at i hour after treatment and decreased with time. By electronmicroscope, we observed dilated lacunae, intercellular lipid structural abnormalities and loss of normal calcium gradient. Conclusion: The possible domains of the epidermis interacting with oleic acid as a penetration enhancer are the lacunae and lipid bilayer by EM. The suggested pathomechanism of the epidermal changes, epidermal proliferation and hyperkeratosis was increased DNA synthesis of epidermal cells by the loss of epidermal calcium gradient in chronic barrier impairment.