Visualization of Iontophoretic Transport Paths in Cultured and Animal Skin Models

Abstract

Physiological structures associated with iontophoretic paths in hairless mouse skin and two cultured skin models ("EpiDerm" by Mattek, Corp., and "SKIN2" by Advanced Tissue Sciences, Inc.) are reported. Visualization of ionic paths at current densities between 20 and 100 microA/ cm2 is accomplished by the counterdirectional transport of Fe(CN)6(4-) and Fe3+, resulting in the controlled precipitation of colloidal Prussian blue, Fe4[Fe(CN)6]3, at sites of high ionic conductivity. Examination of the Fe4[Fe(CN)6]3-stained tissues using optical microscopy allows unequivocal assignment of iontophoretic paths to physiological structures in the stratum corneum. Deposition of Fe4[Fe(CN)6]3 occurs exclusively at hair follicles in hairless mouse skin, indicating that these appendages provide highly conductive porous paths during iontophoresis. In contrast, the counterdirectional transport of Fe(CN)6(4-) and Fe3+ across cultured skin models, which lack appendages, results in the deposition of Fe4-[Fe(CN)6]3 along the boundaries of corneocytes. This observation suggests that paracellular iontophoretic transport through lipid bilayer regions is the predominant transport path in the absence of low-resistance pores.

Effect of Permeation Enhancer Pretreatment on the Iontophoresis of Luteinizing Hormone Releasing Hormone (LHRH) Through Human Epidermal Membrane (HEM)

“…Visualization studies have suggested the primary route through the stratum corneum is the located in or near the skin appendages 19. Other biophysical investigations indicate that ion and water transport occurs, at least in part, through the polar region of the intercellular lipid lamellae 20,21. Therefore, enhancers that exert an effect in these regions are more likely to synergistically enhance iontophoretic permeability.…”

The Pretreatment Effect of Chemical Skin Penetration Enhancers in Transdermal Drug Delivery Using Iontophoresis

“…The changes by iontophoresis, including decreases in skin impedance [27,28], deprivation of epidermal calcium [25], and the suggestion that the proposed pathways of iontophoresis are pores [29][30][31], hair follicles [32] and sweat ducts imply that spaces with decreased electric impedance may be easy iontophoretic pathways.…”

Analysing the Skin Barrier from Down Under

“…In the case of iontophoretic transport, the transappendageal route via the hair follicles and sweat ducts predominates [39]. Lai and Roberts [38] showed that most small solutes are transported through a pore with radii of 6.8-17 Å, which is consistent with transport through the polar intercellular and transappendageal pathway.…”