Transdermal diffusion, spatial distribution and physical state of a potential anticancer drug in mouse skin as studied by diffusion and spectroscopic techniques

Understanding the efficiency of a transdermal medical drug requires the characterization of its diffusion process, including its diffusion rate, pathways and physical state. The aim of this work is to develop a strategy to achieve this goal. FTIR spectroscopic imaging in conjunction with a Franz cell and HPLC measurements were used to examine the transdermal penetration of deuterated tert-butyl phenylchloroethylurea (tBCEU), a molecule with a potential anticancer action. tBCEU has been solubilized in an expedient solvent mixture and its diffusion in hairless mouse skin has been studied. The results indicate that tBCEU diffuses across the skin for more than 10 hours with a rate comparable to selegiline, an officially-approved transdermal drug. IR image analyses reveal that after 10 hours, tBCEU penetrates skin and that its spatial distribution does not correlate with neither the distribution of lipids nor proteins. tBCEU accumulates in cluster domains but overall low concentrations are found in skin. FTIR spectroscopic imaging additionally reveals that tBCEU is in a crystalline form. The results suggest that tBCEU is conveyed through the skin without preferential pathway. FTIR spectroscopic imaging and transdermal diffusion measurements appear as complementary techniques to investigate drug diffusion in skin.