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The enhancing effects of various vehicles on the in vitro permeation of a hydrophilic model drug, 5-fluorouracil (5-FU), or a lipophilic model drug, tolnaftate (TN), through human nail plates were investigated using a modified side-by-side diffusion cell. Tip pieces from the 5th finger-nail, clipped from healthy volunteers, were used in this permeation study. The swelling and softening properties of the nail pieces were also measured in each vehicle. The weights and stresses of the nail pieces were dramatically changed after immersion in aqueous solvents containing N-acetyl-L-cysteine (AC) or 2-mercaptoethanol (ME). However, no significant change in the physicochemical properties of the nail pieces was found in the lipophilic vehicles. Thus, the water content in the nail plates absorbed from vehicles may relate to their physicochemical properties. Although keratin-softening agents and new skin permeation enhancers did not significantly promote 5-FU permeation compared with water alone, the flux from solvent systems containing AC or ME was substantially higher. In addition, TN permeation from solvents containing AC or ME could be measured, whereas that from other solvents was undetectable. When the AC concentration was increased, the 5-FU permeation and the nail weight increased and the stress of each nail piece decreased. It is concluded from these experimental results that AC and ME may be useful as enhancers for increasing drug permeation through the human nail plate.

Enhancing Effect of N-Acetyl-L-cysteine or 2-Mercaptoethanol on the in Vitro Permeation of 5-Fluorouracil or Tolnaftate through the Human Nail Plate.