title: Effect of penetration enhancers and iontophoresis on the ultrastructure and cholecystokinin-8 permeability through porcine skin.
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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo 58105, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Bhatia
authors.forename: S
authors.initials: S
authors.lastname: Gao
authors.forename: T P
authors.initials: TP
authors.lastname: Freeman
authors.forename: J
authors.initials: J
authors.lastname: Singh
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007478:Iontophoresis; D008854:Microscopy, Electron; D012867:Skin / Q000187:drug effects / Q000648:ultrastructure*; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine
chemical_list: D002766:Cholecystokinin