Effect of Penetration Enhancers and Iontophoresis on the Ultrastructure and Cholecystokinin-8 Permeability through Porcine Skin

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Abstract
The present study explores the effect of chemical penetration enhancers and iontophoresis on the in vitro permeability of cholecystokinin-8 (CCK-8) through porcine epidermis and on the ultrastructural changes in stratum corneum as observed by transmission electron microscopy (TEM). Enhancer [i.e., ethanol (EtOH), and 10% oleic acid in combination with ethanol (OA/EtOH)] pretreatment significantly increased (p < 0.01) the permeability coefficient of CCK-8 in comparison with the control (pretreated epidermis without enhancer). Iontophoresis further increased the permeability of CCK-8 (p < 0.01) through the enhancer-pretreated epidermis in comparison with the control. These results showed the synergistic effect of iontophoresis and enhancers such as OA/EtOH that provides an additional driving force to maintain and control the target flux of CCK-8. The ultrastructure of stratum corneum treated with ethanol demonstrated a loss of structural components in the superficial stratum corneum cell layers. OA/EtOH transformed the highly compact cells of stratum corneum into a looser network of filaments, creating an increased free volume and greater intracellular surface area. Treatment of stratum corneum with OA/EtOH followed by iontophoresis resulted in further swelling of stratum corneum cell layers. In conclusion, OA/EtOH in combination with iontophoresis increased the permeability of CCK-8 by loosening and swelling of stratum corneum cell layers.