Evaluation of Skin Barrier Function Using Direct Current III: Effects of Electrode Distance, Boundary Length and Shape

Abstract

Transdermal drug delivery can avoid first-pass metabolism, which is the greatest disadvantage of oral administration. However, the percutaneous absorption of drugs with a high molecular weight and hydrophilic properties is not sufficient due to the barrier function of the skin. To enhance the absorption, several investigations using vehicles, 1,2) chemical enhancers, [3][4][5][6] iontophoresis, 7-9) electroporation 10,11) and phonophoresis 12,13) have been performed. We have focused on iontophoresis in terms of the enhancement of the amount of drug delivered by current with low skin irritation. In a previous study, we predicted that the amount of drug that migrated in the skin was determined by a synergistic effect of both current application and enhanced passive diffusion due to the reduction in barrier function.14)The prediction was proved by the measurement of the distribution using indomethacin as a model drug. 15) In these studies, the accumulation of drug in the stratum corneum contributed to enhanced passive diffusion due to the reduction in barrier function. On the other hand, the accumulation from dermis to upper dermis was attributed to a passage of current. Further, a novel method for analyzing the reduction in barrier function under constant voltage was proposed.16) With this method, the barrier function was defined as resistance, which represented the sum of exponential functions of surface and skin resistance. In addition, the evaluation was carried out using the initial value and rate constant of the surface resistance. Using this method, effects of conductivity in the adhesive pad, voltage, the distance between electrodes and electrode area on the barrier function were evaluated. Furthermore, the influence of a pulsed direct current, which could prevent skin polarization and irritation was investigated. 17)The reduction in barrier function brought about by the application of sine and rectangular waveforms with a 75% duty cycle was almost the same as that caused by the application of direct current. Considering the skin polarization, the pulsed currents were more suitable.In the evaluation of changing electrode area, 16) although the initial value of surface resistance increased with increasing electrode area, no change of rate constant was observed. The rate constant showed the damping of the surface resistance, i.e., the barrier function. These phenomena contributed to the higher current density in the portion adjacent to the other electrode. Therefore, we investigated the electrode disposition and shape considering the reduction in barrier function as well as effective delivery of drugs into the skin. Similar results were reported by Haga et al. 18) They prepared electrodes with different boundary lengths using a photoeching technique, and then observed the skin distribution of 6-carboxyfluorescein (6-CF) under constant voltage. In that paper, the topical distribution of 6-CF in the skin was recognized in both boundary portions, i.e., the portion adjacent to the other electrode. They suggested ...

Effect of continuous vs pulsed iontophoresis of treprostinil on skin blood flow

“…On the one hand, the efficiency of iontophoretic transport depends on the quantity of current delivered (i.e. product of intensity by time) (Kalia et al, 2004), but on the other hand it also depends on the effect of the current itself on the electrical properties of the skin (Chen and Chien, 1996;Chizmadzhev et al, 1998;Kanebako et al, 2002aKanebako et al, , 2003Kanebako et al, , 2002bNair and Panchagnula, 2004). In particular, it is known that using a relatively high voltage during iontophoresis facilitates the transport of drugs by a mechanism of pore formation which decreases the skin's resistance (Glaser et al, 1988;Sims et al, 1992;Inada et al, 1994).…”

Desenvolvimento de sistemas de liberação para a administração tópica passiva e iontoforética do minoxidil no tratamento da alopecia androgênica

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